Pulmonary hypertension in advanced heart failure with reduced ejection fraction.  What are the consequences of the new definition?

Pulmonary hypertension in advanced heart failure with reduced ejection fraction. What are the consequences of the new definition? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pulmonary hypertension in advanced heart failure with reduced ejection fraction. What are the consequences of the new definition? Samuel Vysočanský, Milan Luknár, Peter Lesný, Marcela Danková, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9382853/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Background The recent definition of pulmonary hypertension (PH) has expanded the category of combined pre- and post-capillary (CPC) PH. Its impact on PH prevalence and prognosis in advanced heart failure with reduced ejection fraction (HFrEF) remains unknown. Methods We retrospectively analyzed 175 HFrEF patients evaluated for heart transplantation, all of whom underwent comprehensive invasive and non-invasive work-up. To assess the prognostic impact of the updated PH definition, survival was compared according to the presence of PH and its phenotype. Results PH was present in 83% of patients, 76% of these met CPC PH criteria. Applying the 2015 definition, 77% of patients would have had PH, with 46% of them classified as CPC PH. Presence of PH correlated with markers of advanced HFrEF course, but only larger left atrial diameter (HR 1.158; 95% CI 1.020–1.315; p = 0.024) and lower TAPSE (HR 0.811; 95% CI 0.674–0.976; p = 0.027) remained independent predictors. CPC PH patients were older, with higher prevalence of renal insufficiency, diabetes and worse central hemodynamics. Higher age (HR 1.045; 95% CI, 1.000-1.091; p = 0.048), systolic pulmonary artery pressure determined non-invasively (HR 1.064; 95% CI, 1.018–1.111; p = 0.006) and pulmonary artery wedge pressure (HR 1.131; 95% CI, 1.015–1.261; p = 0.026) were only predictors of CPC PH. Presence of both PH and CPC PH was associated with worse 2-year outcome, defined as implantation of mechanical circulatory support or all-cause mortality. Conclusions The new PH definition minimally affects PH prevalence in advanced HFrEF but substantially increases CPC PH group, which remains associated with adverse prognosis. HFrEF pre- and post-capillary pulmonary hypertension heart transplant Figures Figure 1 Figure 2 Figure 3 1. Introduction Post-capillary PH, a common component of the HF syndrome, results from passive transmission of elevated left ventricle filling pressure [ 1 ]. 2022 ESC PH guidelines redefined PH as mean pulmonary artery pressure (mPAP) > 20 mm Hg [ 2 , 3 ]. Post-capillary PH reamins being defined by pulmonary artery wedge pressure (PAWP) > 15 mm Hg, while pulmonary vascular resistance (PVR) > 2 WU defines a combined pre- and post-capillary (CPC) phenotype [ 4 , 5 ]. Pre-capillary vasculature remodelling in CPC PH, referred to as pulmonary vascular disease (PVD), contributes to right ventricular dysfunction and is associated with adverse outcomes [ 6 , 7 ]. The reported prevalence of PH in HFrEF varies widely depending on patient characteristics and diagnostic modality, ranging from 35–48% in echocardiographic studies [ 8 , 9 ] to 46–72% in invasive right-heart catheterization (RHC) studies [ 9 , 10 ]. However, these data largely reflect patients with stable or de novo HFrEF. Data regarding the prevalence of PH in advanced HFrEF are scarce. Previous RHC-based studies were conducted using earlier PH definitions. The impact of the 2022 classification on PH prevalence, phenotypes, and associated factors in advanced HFrEF remains unclear. This study aims to analyze the prevalence, characteristics, predictors of PH, its phenotypes and survival in patients with advanced chronic HFrEF according to the recent definition [ 2 ] in current era. 2. Patients and methods 2.1. Study design We retrospectively analyzed patients hospitalized between 2017 and 2020 for advanced HFrEF, regardless of disease duration. The main inclusion criterion was left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) < 40%. Exclusion criteria were as follows: age < 18 years, patients with an LVAD, patients with severe lung disease (total lung capacity < 60% of predicted, forced expiratory volume < 60% of predicted, the need for long-term oxygen therapy or PaO2 < 60 mmHg). All patients underwent RHC. Selected clinical, anthropometric, laboratory, electrocardiographic, echocardiographic, and hemodynamic data were extracted from the medical records maintained in a standard protocol manner [ 11 ]. 2.2. Right heart catheterization methodology Right heart catheterization (RHC) was performed using a Swan-Ganz thermodilution catheter under standard conditions within 24 hours of echocardiography and peripheral blood sampling. In patients with congestive signs, RHC was performed after achieving euvolemia. 2.3. Definitions Patients were classified into one of three groups according to the ESC guidelines (2) - patients in whom invasive testing did not prove the presence of PH, patients with IPC PH and CPC PH respectively. The IPC PH was defined as mPAP > 20 mm Hg, PAWP > 15 mm Hg, PVR ≤ 2 WU. If PVR was > 2 WU, patients were classified as CPC PH. For survival analysis, 2-year survival was assessed, with the endpoint defined as either mechanical circulatory support implantation or all-cause mortality. Urgent heart transplantation is not available in our region and was therefore not considered a relevant endpoint. 2.4. Statistics Continuous variables are expressed as mean ± SD and categorical variables as n (%). Group differences were assessed using Student’s t-test or chi-square test. Logistic regression was used to identify variables associated with PH phenotypes, presented as odds ratios (OR). Survival analysis was performed using Kaplan–Meier estimates and Cox proportional hazards regression, with results expressed as hazard ratios (HR). A p-value < 0.05 was considered statistically significant. The predictive performance of non-invasive sPAP for CPC PH was assessed using receiver operating characteristic (ROC) curves and the area under the curve (AUC). 3. Results 3.1. Baseline characteristics A total of 175 patients were enrolled (39 women). The predominant etiology was dilated cardiomyopathy, followed by ischemic heart disease. Less frequent causes included hypertensive heart disease, burnt-out hypertrophic cardiomyopathy, non-compaction cardiomyopathy, chronic myocarditis, and valvular heart disease. The median age was 54 years, and mean LVEF was 21.9 ± 6.7%. The mean duration from HF diagnosis to RHC was 112 ± 103 months. Most patients were in NYHA class III (124 patients) or class IV (40 patients). Baseline clinical characteristics are summarized in Table 1 . Table 1 Baseline characteristics Number of pts 175 Men (n/%) 136/78 Age (years) 54.1 ± 10.8 HF etiology DCMP (n/%) 73 (42) CAD (n/%) 66 (38) Other (n/%) 36 (20) Duration of the HF (months) 112 ± 103 LVEF (%) 21.9 ± 6.7 NYHA I/II/III/IV (n) 0/11/124/40 CAD, coronary artery disease, DCMP, dilated cardiomyopathy, HF, heart failure, LVEF, left ventricle ejection fraction, NYHA, New York Heart Association 3.2. Non-invasive and invasive characteristics Post-capillary PH was present in 83% of patients, with 24% of them classified as IPC PH and 76% as CPC PH (Fig. 1 ). Patients with PH had longer HF duration, lower blood pressure. Echocardiography revealed more advanced cardiac remodeling, including larger left atrium and right ventricle with impaired systolic function. PH patients were more likely to have moderate or severe mitral regurgitation (MR), while there was no significant difference in either the presence or the severity of tricuspid regurgitation (TR), but a trend could be observed (p = 0.06). PH was also associated with a higher prevalence of atrial fibrillation and renal insufficiency (KDIGO G2–G5, defined as eGFR < 90 mL/min/1.73 m²). Among laboratory markers, PH was linked to lower serum sodium and higher concentrations of NT-proBNP, uric acid (UA), and liver enzymes gamma-glutamyl transferase (GMT), serum bilirubin (bil). The only electrocardiographic parameter showing significant difference was a wider QRS complex in PH group. Lung function parameters (FEV₁, FVC, FEV₁/FVC) were comparable between groups. Hemodynamic parameters were not compared between PH and non-PH patients, as differences in pulmonary pressures inherently define PH. CPC PH patients were older, had lower exercise capacity, and a higher prevalence of renal insufficiency and type 2 diabetes. Among non-invasive parameters, only higher sPAP differentiated CPC PH from IPC PH. Hemodynamic impairment was more pronounced in CPC PH, while RAP did not differ between groups (10.9 ± 6.2 vs 11.9 ± 5.4 mm Hg; p = 0.37). Detailed data are provided in Tables 2 and 3 . Table 2 Differences in observed parameters between patients with and without PH PH – (mPAP ≤ 20 mmHg) PH + (mPAP > 20 mmHg) p Clinical parameters Duration of disease (months) 46 ± 55 81 ± 67 0.005 Age (years) 52 ± 11 51 ± 14 0.590 Sex (M/F) (%) 72/28 79/21 0.453/0.414 SBP (mmHg) 120 ± 20 108 ± 13 0.004 DBP (mmHg) 75 ± 15 70 ± 10 0.038 Heart rate (min − 1 ) 75 ± 13 79 ± 14 0.165 Weight (kg) 85 ± 17 84 ± 16 0.639 BMI (kg/m 2 ) 28 ± 5 27 ± 4 0.533 Etiology (CAD/%) 34 38 0.319 Etiology (DCMP/%) 38 42 0.289 NYHA II/III/IV (%) 14/72/14 5/71/25 0.112/0.156/0.097 6-MWD (m) 351 ± 143 402 ± 117 0.085 Echocardiographic parameters LVEF (%) 26 ± 8 21 ± 6 < 0.0001 LVEDD (mm) 65 ± 13 69 ± 11 0.081 LA (mm) 45 ± 7 51 ± 7 < 0.0001 MR (moderate - severe) (%) 13 42 0.013 TR (moderate - severe) (%) 10 31 0.058 RV (mm) 34 ± 8 39 ± 9 0.008 TAPSE (mm) 18 ± 6 14 ± 4 < 0.0001 Laboratory parameters UA (umol/L) 382 ± 103 469 ± 141 0.002 Na (mmol/L) 141 ± 2 140 ± 3 0.011 NT-proBNP (ug/L) 1976 ± 2376 4565 ± 4087 < 0.0001 Creatinine (umol/L) 123 ± 147 101 ± 29 0.422 Urea (mmol/L) 6.9 ± 3.3 7.8 ± 3.4 0.182 CKD-EPI (mL/s) 1.23 ± 0.44 1.24 ± 0.32 0.980 ALP (ukat/L) 1.27 ± 0.34 1.54 ± 0.77 0.005 AST (ukat/L) 0.39 ± 0.11 0.54 ± 1.04 0.437 ALT (ukat/L) 0.44 ± 0.20 1.12 ± 5.93 0.534 GMT (ukat/L) 0.77 ± 0.70 2.01 ± 2.26 < 0.0001 Bil (umol/L) 13 ± 12 19 ± 10 0.004 Fe (umol/L) 15 ± 5 15 ± 11 0.863 Ferritin (ug/L) 151 ± 125 144 ± 139 0.816 Hemoglobin (g/L) 140 ± 17 136 ± 18 0.253 ECG parameters PQ (ms) 0.168 ± 0.040 0.184 ± 0.039 0.085 QRS (ms) 0.098 ± 0.023 0.117 ± 0.028 0.001 LBBB (%) 10 14 0.341 Comorbidities Hypertension (%) 48 51 0.813 Dyslipidaemia (%) 55 44 0.263 Diabetes mellitus (%) 28 27 0.923 Atrial fibrillation (%) 17 36 0.031 Renal insuficiency (%) 59 29 0.002 Pulmonary function test FEV1 (%) 87 ± 21 80 ± 14 0.059 FVC (%) 86 ± 16 80 ± 14 0.084 FEV1/FVC (%) 81 ± 9 81 ± 7 0.996 Hemodynamic parameters RAP (mmHg) 6.2 ± 3.9 11.6 ± 5.6 < 0.0001 sPAP (mmHg) 26.0 ± 4.0 51.0 ± 14.0 < 0.0001 dPAP (mmHg) 12.0 ± 3.0 27.0 ± 7.0 < 0.0001 mPAP (mmHg) 17.0 ± 2.0 37.0 ± 9.0 < 0.0001 PAWP (mmHg) 10.0 ± 2.0 26.0 ± 6.0 < 0.0001 TPG (mmHg) 7.2 ± 2.3 11.4 ± 4.5 < 0.0001 DPG (mmHg) 2.0 ± 1.6 1.8 ± 2.9 0.731 PVR (WU) 1.6 ± 0.6 3.0 ± 1.4 < 0.0001 CO (l/min) 4.7 ± 1.1 3.9 ± 1.1 < 0.0001 CI (l/min/m2) 2.4 ± 0.6 2.0 ± 0.5 0.001 ALP, alkaline phosphatase, ALT, alanine aminotransferase, AST, aspartate aminotransferase, Bil, bilirubin, BMI, body mass index, CAD, coronary artery disease, CI, cardiac index, CKD-EPI, chronic kidney disease epidemiology collaboration, CO, cardiac output, DBP, diastolic blood pressure, DCMP, dilated cardiomyopathy, DPAP, diastolic pulmonary artery pressure, DPG, diastolic pressure gradient, Fe, iron, FEV1, forced expiratory volume, FVC, functional vital capacity, GMT, gamma- glutamyl transferase, LA, left atrium, LBBB, left bundle brunch block, LVEDD, left ventricle end-diastolic diameter, LVEF, left ventricle ejection fraction, MPAP, mean pulmonary artery pressure, MR, mitral regurgitation, NT-proBNP, N-terminal pro b-type natriuretic peptide, PAWP, pulmonary artery wedge pressure, PVR, pulmonary vascular resistance, RAP, right atrial pressure, RBBB, right bundle brunch block, RV, right ventricle, SPAP, systolic pulmonary artery pressure, SPB, systolic blood pressure, TAPSE, tricuspid annular plane systolic excursion, TPG, transpulmonary pressure gradient, TR, tricuspid regurgitation, UA, uric acid Table 3 Differences in observed parameters between IPC PH and CPC PH patients IPC PH CPC PH p Clinical parameters Duration of disease (months) 73 ± 63 83 ± 69 0.449 Age (years) 47 ± 13 54 ± 10 0.001 Sex (M/F) (%) 74/26 80/20 0.578/0.446 SBP (mmHg) 107 ± 13 108 ± 13 0.763 DBP (mmHg) 71 ± 11 70 ± 10 0.759 Heart rate (min − 1 ) 79 ± 17 79 ± 13 0.950 Weight (kg) 85 ± 18 83 ± 15 0.547 BMI (kg/m 2 ) 27 ± 5 27 ± 4 0.778 Etiology (CAD/%) 23 43 0.092 Etiology (DCMP/%) 51 40 0.217 NYHA II/III/IV (%) 3/77/20 5/68/26 0.592/0.478/0.378 6-MWD (m) 439 ± 74 390 ± 126 0.036 Echocardiographic parameters LVEF (%) 22 ± 7 21 ± 6 0.161 LVEDD (mm) 70 ± 14 68 ± 9 0.373 LA (mm) 49 ± 7 45 ± 7 0.205 MR (moderate – severe) (%) 34 45 0.515 TR (moderate - severe) (%) 33 41 0.062 RV (mm) 38 ± 8 39 ± 9 0.345 TAPSE (mm) 15 ± 5 14 ± 4 0.576 sPAP (mmHg) 44 ± 13 56 ± 14 < 0.001 TAPSE/sPAP (mm/mmHg) 0.31 ± 0.11 0.27 ± 0.11 0.079 Laboratory parameters UA (umol/L) 474 ± 139 467 ± 142 0.816 Na (mmol/L) 139 ± 4 140 ± 3 0.419 NT-proBNP (ug/L) 3823 ± 2560 4803 ± 4452 0.218 Creatinine (umol/L) 97 ± 25 102 ± 30 0.360 Urea (mmol/L) 7.2 ± 3.0 8.0 ± 3.5 0.200 CKD-EPI (mL/s) 1.31 ± 0.26 1.21 ± 0.34 0.112 ALP (ukat/L) 1.44 ± 0.53 1.56 ± 0.83 0.426 AST (ukat/L) 0.50 ± 0.22 0.55 ± 1.19 0.801 ALT (ukat/L) 0.48 ± 0.31 1.33 ± 6.81 0.471 GMT (ukat/L) 1.74 ± 1.68 2.09 ± 2.41 0.443 Bil (umol/L) 18 ± 10 19 ± 11 0.524 Fe (umol/L) 14 ± 7 16 ± 12 0.377 Ferritin (ug/L) 170 ± 190 135 ± 116 0.258 Hemoglobin (g/L) 135 ± 17 136 ± 18 0.833 ECG parameters PQ (ms) 0.175 ± 0.038 0.186 ± 0.039 0.238 QRS (ms) 0.109 ± 0.025 0.120 ± 0.028 0.100 LBBB (%) 17 13 0.304 Comorbidities Hypertension (%) 43 53 0.288 Dyslipidaemia (%) 40 45 0.600 Diabetes mellitus (%) 11 32 0.019 Atrial fibrillation (%) 34 36 0.850 Renal insufficiency (%) 14 33 0.012 Pulmonary function test FEV1 (%) 81 ± 15 79 ± 14 0.518 FVC (%) 82 ± 14 79 ± 13 0.293 FEV1/FVC (%) 81 ± 8 82 ± 7 0.981 Hemodynamic parameters RAP (mmHg) 10.9 ± 6.2 11.9 ± 5.4 0.376 sPAP (mmHg) 38.0 ± 7.0 55.0 ± 13.0 < 0.0001 dPAP (mmHg) 23.0 ± 5.0 29.0 ± 6.0 < 0.0001 mPAP (mmHg) 29.0 ± 5.0 40.0 ± 9.0 < 0.0001 PAWP (mmHg) 22.0 ± 5.0 27.0 ± 6.0 < 0.0001 TPG (mmHg) 7.3 ± 1.8 12.7 ± 4.3 < 0.0001 DPG (mmHg) 1.0 ± 1.8 2.0 ± 3.1 0.022 PVR (WU) 1.6 ± 0.4 3.5 ± 1.4 < 0.0001 CO (l/min) 4.6 ± 1.3 3.7 ± 0.9 < 0.0001 CI (l/min/m2) 2.3 ± 0.5 1.9 ± 0.4 < 0.0001 ALP, alkaline phosphatase, ALT, alanine aminotransferase, AST, aspartate aminotransferase, Bil, bilirubin, BMI, body mass index, CAD, coronary artery disease, CI, cardiac index, CKD-EPI, chronic kidney disease epidemiology collaboration, CO, cardiac output, DBP, diastolic blood pressure, DCMP, dilated cardiomyopathy, DPAP, diastolic pulmonary artery pressure, DPG, diastolic pressure gradient, Fe, iron, FEV1, forced expiratory volume, FVC, functional vital capacity, GMT, gamma-glutamyl transferase, LA, left atrium, LBBB, left bundle brunch block, LVEDD, left ventricle end-diastolic diameter, LVEF, left ventricle ejection fraction, MPAP, mean pulmonary artery pressure, MR, mitral regurgitation, NT-proBNP, N-terminal pro b-type natriuretic peptide, PAWP, pulmonary artery wedge pressure, PVR, pulmonary vascular resistance, RAP, right atrial pressure, RBBB, right bundle brunch block, RV, right ventricle, SPAP, systolic pulmonary artery pressure, SPB, systolic blood pressure, TAPSE, tricuspid annular plane systolic excursion, TPG, transpulmonary pressure gradient, TR, tricuspid regurgitation, UA, uric acid 3.3. Predictors of PH and CPC PH In univariate analysis, multiple clinical, echocardiographic, and laboratory variables were associated with PH, all of them being summarized in Table 4 . sPAP was excluded as it represents a surrogate marker of PH. Table 4 Variables associated with the presence of PH Variable Univariate Odds Ratio (95% CI) p value Multivariate Odds Ratio (95% CI) p value Duration of disease 1.060 (1.012–1.110) 0.013 1.044 (0.908–1.199) 0.547 SBP 0.079 (0.677–0.896) < 0.001 0.910 (0.660–1.254) 0.564 LVEF 0.603 (0.499–0.810) 0.001 0.846 (0.395–1.812) 0.667 LA 1.136 (1.059–1.218) < 0.001 1.158 (1.020–1.315) 0.024 MR (moderate/severe) 4.593 (1.520-13.883) 0.007 3.600 (0.339–38.178) 0.288 RV 1.083 (1.021–1.148) 0.008 0.890 (0.774–1.022) 0.098 TAPSE 0.850 (0.773–0.935) 0.001 0.811 (0.674–0.976) 0.027 CI 0.887 (0.822–0.956) 0.002 0.879 (0.704–1.098) 0.256 UA 1.060 (1.021–1.101) 0.002 1.065 (0.961–1.181) 0.228 NT-proBNP 1.047 (1.018–1.076) 0.001 0.879 (0.982–1.074) 0.246 GMT 1.129 (1.044–1.222) 0.002 1.062 (0.925–1.219) 0.393 Bil 1.086 (1.024–1.151) 0.006 0.959 (0.831–1.107) 0.565 QRS 1.423 (1.134–1.784) 0.002 1.019 (0.648–1.602) 0.935 Bil, bilirubin, CI, cardiac index, GMT, gamma-glutamyl transferase, LA, left atrium, LVEF, left ventricle ejection fraction, MR, mitral regurgitation, NT-proBNP, N-terminal pro b-type natriuretic peptide, RV, right ventricle, SPB, systolic blood pressure, TAPSE, tricuspid annular plane systolic excursion, UA, uric acid Table 5 Variables associated with the presence of CPC PH Variable Univariate Odds Ratio (95% CI) p value Multivariate Odds Ratio (95% CI) p value Age 1.055 (1.020–1.092) 0.002 1.045 (1.000-1.091) 0.048 Renal insufficiency 3.000 (1.076–8.367) 0.036 2.254 (0.484–10.497) 0.300 Diabetes mellitus 3.569 (1.170-10.891) 0.025 0.940 (0.217–4.066) 0.934 sPAP 1.075 (1.035–1.118) < 0.001 1.064 (1.018–1.111) 0.006 PAWP 1.179 (1.087–1.279) < 0.001 1.131 (1.015–1.261) 0.026 PAWP, pulmonary artery wedge pressure SPAP, systolic pulmonary artery pressure CPC PH, combined pre- and post-capillary pulmonary hypertension, IPC PH, isolated post-capillary pulmonary hypertension, PH – pulmonary hypertension After multivariate adjustment, only left atrial diameter and TAPSE remained independent predictors of PH. For the CPC PH phenotype, age and sPAP were the only independent non-invasive predictors, while PAWP was the only independent invasive predictor. For differentiating post-capillary PH phenotypes, an sPAP value > 55 mm Hg obtained by echocardiography identified CPC PH with moderate accuracy (C-statistic 0.76; sensitivity 47%; specificity 81%). 3.4. Prognostic value of the new PH definiton For survival analysis, patients who underwent non-urgent heart transplantation (HTx) were excluded, as many of them might have had advanced yet relatively stable HFrEF course. In total, 42 patients received HTx (11 with IPC PH, 26 with CPC PH and 5 without PH). The median interval between the first RHC and HTx was 1006 ± 215 days in patients without PH, 397 ± 301 days in those with IPC PH and 183 ± 128 days in the CPC PH group. The primary endpoint was a composite of all-cause mortality, urgent listing for HTx, or urgent mechanical circulatory support (MCS) implantation. During follow-up, 59 patients died, 34 required MCS implantation, and 2 were listed as urgent HTx candidates. The median time from the reference RHC to the endpoint was 775 ± 710 days. Survival according to PH presence is shown in Fig. 2 . Two-year survival was assessed from the reference RHC. One-year mortality was 36% in patients with PH and 3% in patients without PH; two-year mortality was 53% and 12%, respectively. A significant difference in survival was also observed across PH phenotypes (p = 0.039) (Fig. 3 ). In the IPC PH group, one-year mortality was 21% compared with 38% in the CPC PH group. After two years, mortality increased to 37% in IPC PH and 62% in CPC PH. 4. Discussion 4.1. PH prevalence according to the new definition Applying the new definition, PH was present in 83% of patients, compared with 77% using the previous mPAP ≥ 25 mm Hg threshold, indicating minimal impact on overall prevalence. The slightly lower prevalence of PH, 77% [ 8 ], resp. 68% [ 12 ] in patients with HF according to the findings of other authors is probably related to less advanced HF in the populations studied and not to the definition of PH being valid at the time. Using the lower mPAP as the PH defining criterion, PH was present in 62% [ 13 ] and 64% [ 14 ] of patients with less advanced stages of HFrEF. A recent multicenter study reported a modest increase in PH prevalence with the updated criteria, although comparison is limited by a high proportion of HFpEF patients [ 15 ]. Overall, these findings suggest that PH prevalence in HF is driven primarily by disease severity and patient characteristics rather than the specific mPAP cutoff. Our results further support that PH represents a common feature of advanced HFrEF even in the modern therapeutic era of HF. Lowering the PVR threshold for CPC PH represents a more impactful change. This modification was largely based on data showing increasing risk of death and hospitalization from PVR ≥ 2.2 WU, although this association was less pronounced in post-capillary PH [ 16 ]. Therefore, it can be debated whether a different, higher, PVR cut-off value should be chosen to express clinically significant PVD in patients with post-capillary PH. In our cohort, applying the new criteria led to a disproportionate increase in CPC PH prevalence (76%), compared with 46% using the 2015 definition. Similarly, Fauvel et al. reported a disproportionate rise in CPC PH prevalence from 42% to 67% when adopting the lowered PVR threshold. 4.2. Predictors of PH The high prevalence of PH in our cohort reflects the advanced stage of HFrEF [ 17 ], with up to 94% of patients being in NYHA classIII/IV. The presence of PH was associated with a prognostically unfavourable patient profile - lower systolic blood pressure, lower LVEF, higher natriuretic peptide and UA levels [ 18 ]. Several studies, including meta-analyses, have shown that elevated serum UA levels predict increased risk of death and hospitalizations for PH [ 19 – 21 ] and inversely correlate with CO [ 22 , 23 ]. The impact of MR on the development of PH in the context of HFrEF is well known [ 24 ], as confirmed by our results showing the association of PH with moderate and severe MR. Moderate or severe MR has been shown to be an independent predictor of PH in the group of patients with advanced HFrEF, along with TR and the duration of disease [ 25 , 26 ]. Right ventricular (RV) dysfunction represents a downstream consequence of PH, potentially affect peripheral organ functions [ 27 – 30 ]. RV dysfunction was more pronounced in PH affected patients, accompanied by a cholestatic laboratory profile consistent with advanced right-sided HF. Finally, QRS prolongation was associated with PH, likely reflecting more advanced myocardial remodeling and its known link to worse prognosis [ 31 , 32 ]. 4.3. Predictors of CPC PH Distinguishing IPC PH from CPC PH using clinical and non-invasive parameters remains challenging. CPC PH was more frequent in older patients and those with diabetes and renal insufficiency. The association of an older age and renal insufficiency with impaired pulmonary vasculature previously described in HFpEF patients [ 33 ] likely reflects proinflammatory state leading to the endothelial dysfunction rather than pulmonary disease [ 34 , 35 ]. Consistently, spirometric parameters did not differ between groups, supporting a limited role of primary lung pathology. Among non-invasive measures, only sPAP differentiated PH phenotypes, with values > 55 mm Hg identifying CPC PH with acceptable accuracy. This finding may facilitate non-invasive phenotyping and patient selection in studies targeting PVD as therapeutic target in HFrEF. 4.4. Outcomes according to the hemodynamic profile PH in HF is a strong determinant of mortality irrespective of LVEF. In our cohort, its adverse prognostic impact persisted despite the lower mPAP threshold, with CPC PH consistently identifying a subgroup at substantially higher risk compared with IPC PH. These results suggest that the CPC PH phenotype may warrant consideration as an additional factor when prioritizing patients on the heart transplant waiting list. To our knowledge, this is the first study to evaluate survival in patients with advanced HF and PH using the modified hemodynamic classification of post-capillary PH. Evidence regarding outcomes in patients with advanced HFrEF and CpcPH remains scarce. A subanalysis of the ESCAPE trial showed no difference in mortality between patients with advanced HFrEF and CpcPH—defined by PVR ≥ 3 WU—and those with PH and PVR < 3 WU [ 36 ]; however, the follow-up period was limited to only 6 months. More recent data examining the impact of the updated PH definition across HF populations, regardless of LVEF, demonstrated significantly worse outcomes in CPC PH even when applying a lower PVR threshold [ 15 ], consistent with our findings.Taken together, these findings suggest that the revised PH definition not only refines hemodynamic classification but also enhances prognostic discrimination, particularly by identifying a high-risk CPC PH phenotype across the HF spectrum. 5. Conclusions The new PH definition has minimal impact on overall PH prevalence in HF but leads to a marked increase in CPC PH, expanding its heterogeneity, which may affect design of future clinical trials targeting the pre-capillary component of PH, such as studies evaluating PAH-specific therapies in post-capillary PH. Non-invasive identification of PVD will therefore be challenging, although sPAP > 55 mm Hg emerged as a useful discriminator in advanced HFrEF. However, the revised definition retains prognostic value by identifying a high-risk CPC PH phenotype, with potential implications for patient monitoring and therapeutic decision-making. Declarations All authors have participated in the work and have reviewed and agree with the content of the article. None of the article contents are under consideration for publication in any other journal or have been published in any journal. The authors have no relevant financial or non-financial interests to declare associated with the topic of this manuscript. Ethical Approval This study protocol was approved by the Ethics Committee of the National Institute of Cardiovascular Diseases, Bratislava, Slovakia, on December 15, 2020. The study was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants. Funding sources There are no funding sources to declare. Author Contribution SV and EG wrote the main manuscript text and prepared all figures. ML, PL, MD, SV performed right-heart catheterisations. AD performed echocardiography examinations. LM was responsible for the statistics. All authors reviewed the manuscript. References Guha A, Amione-Guerra J, Park MH. Epidemiology of Pulmonary Hypertension in Left Heart Disease. Prog Cardiovasc Dis. 2016 Jul-Aug;59(1):3–10. doi: 10.1016/j.pcad.2016.07.001 . Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, et al.; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618–3731. doi: 10.1093/eurheartj/ehac237 . Erratum in: Eur Heart J. 2023;44(15):1312. doi: 10.1093/eurheartj/ehad005. Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009;34(4):888–94. doi: 10.1183/09031936.00145608 . Zeitouni M, Morlon Q, Silvain J, Procopi N, Guedeney P, et al. Implication of the new definition of pulmonary hypertension in patients evaluated for heart transplantation. Int J Cardiol. 2023;384:18–24. doi: 10.1016/j.ijcard.2023.04.048 . Miller WL, Mahoney DW, Michelena HI, Pislaru SV, Topilsky Y, et al. Contribution of ventricular diastolic dysfunction to pulmonary hypertension complicating chronic systolic heart failure. JACC Cardiovasc Imaging. 2011;4(9):946–54. doi: 10.1016/j.jcmg.2011.06.017 . Schmeißer A, Rauwolf T, Groscheck T, Fischbach K, Kropf S, et al. Predictors and prognosis of right ventricular function in pulmonary hypertension due to heart failure with reduced ejection fraction. ESC Heart Fail. 2021;8(4):2968–2981. doi: 10.1002/ehf2.13386 . Benfari G, Antoine C, Miller WL, Thapa P, Topilsky Y, et al. Excess Mortality Associated With Functional Tricuspid Regurgitation Complicating Heart Failure With Reduced Ejection Fraction. Circulation. 2019;140(3):196–206. doi: 10.1161/CIRCULATIONAHA.118.038946 . Szwejkowski BR, Elder DH, Shearer F, Jack D, Choy AM, et al. Pulmonary hypertension predicts all-cause mortality in patients with heart failure: a retrospective cohort study. Eur J Heart Fail. 2012;14(2):162–7. doi: 10.1093/eurjhf/hfr159 . Cappola TP, Felker GM, Kao WH, Hare JM, Baughman KL, et al. Pulmonary hypertension and risk of death in cardiomyopathy: patients with myocarditis are at higher risk. Circulation. 2002;105(14):1663–8. doi: 10.1161/01.cir.0000013771.30198.82 . Miller WL, Grill DE, Borlaug BA. Clinical features, hemodynamics, and outcomes of pulmonary hypertension due to chronic heart failure with reduced ejection fraction: pulmonary hypertension and heart failure. JACC Heart Fail. 2013;1(4):290–299. doi: 10.1016/j.jchf.2013.05.001 . Goncalvesová E. 2022. Manuál diagnostických, indikačných a liečebných postupov. 6. vydanie. Bratislava: Herba, 2022. 131p. ISBN 978-80-8229-25-0 Gerges M, Gerges C, Pistritto AM, Lang MB, Trip P, et al. Pulmonary Hypertension in Heart Failure. Epidemiology, Right Ventricular Function, and Survival. Am J Respir Crit Care Med. 2015;192(10):1234–46. doi: 10.1164/rccm.201503-0529OC . Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol. 2001;37(1):183–8. doi: 10.1016/s0735-1097(00)01102-5 . Ibe T, Wada H, Sakakura K, Ugata Y, Maki H, et al. Combined pre- and post-capillary pulmonary hypertension: The clinical implications for patients with heart failure. PLoS One. 2021;16(3):e0247987. doi: 10.1371/journal.pone.0247987 . Fauvel C, Damy T, Berthelot E, Bauer F, Eicher JC, et al. Post-capillary pulmonary hypertension in heart failure: impact of current definition in the PH-HF multicentre study. Eur Heart J. 2024;45(35):3274–3288. doi: 10.1093/eurheartj/ehae467 . Maron BA, Brittain EL, Hess E, Waldo SW, Barón AE, et al. Pulmonary vascular resistance and clinical outcomes in patients with pulmonary hypertension: a retrospective cohort study. Lancet Respir Med. 2020;8(9):873–884. doi: 10.1016/S2213-2600(20)30317-9 . Crespo-Leiro MG, Metra M, Lund LH, Milicic D, Costanzo MR, et al. Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018;20(11):1505–1535. doi: 10.1002/ejhf.1236 . Metra M, Dinatolo E, Dasseni N. The New Heart Failure Association Definition of Advanced Heart Failure. Card Fail Rev. 2019;5(1):5–8. doi: 10.15420/cfr.2018.43.1 . Miao L, Guo M, Pan D, Chen P, Chen Z, et al. Serum Uric Acid and Risk of Chronic Heart Failure: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2021;8:785327. doi: 10.3389/fmed.2021.785327 . Huang H, Huang B, Li Y, Huang Y, Li J, et al. Uric acid and risk of heart failure: a systematic review and meta-analysis. Eur J Heart Fail. 2014;16(1):15–24. doi: 10.1093/eurjhf/hft132 . Amin A, Vakilian F, Maleki M. Serum uric acid levels correlate with filling pressures in systolic heart failure. Congest Heart Fail. 2011 Mar-Apr;17(2):80–4. doi: 10.1111/j.1751-7133.2010.00205.x . Deis T, Rossing K, Ersbøll MK, Wolsk E, Gustafsson F. Uric acid in advanced heart failure: relation to central haemodynamics and outcome. Open Heart. 2022;9(2):e002092. doi: 10.1136/openhrt-2022-002092 . Givertz MM, Anstrom KJ, Redfield MM, Deswal A, Haddad H, et al. Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) Study. Circulation. 2015;131(20):1763–71. doi: 10.1161/CIRCULATIONAHA.114.014536 . Rosenhek R, Iung B, Tornos P, Antunes MJ, Prendergast BD, et al. ESC Working Group on Valvular Heart Disease Position Paper: assessing the risk of interventions in patients with valvular heart disease. Eur Heart J. 2012;33(7):822-8, 828a, 828b. doi: 10.1093/eurheartj/ehr061 . Torres-Macho J, Delgado-Jiménez JF, Sanz-Salvo J, González-Mansilla A, Sánchez-Sánchez V, et al. Predictors of pulmonary hypertension in patients with end-stage heart failure. Congest Heart Fail. 2012 Jul-Aug;18(4):212–6. doi: 10.1111/j.1751-7133.2011.00277.x . Thomas L, Marwick TH, Popescu BA, Donal E, Badano LP. Left Atrial Structure and Function, and Left Ventricular Diastolic Dysfunction: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(15):1961–1977. doi: 10.1016/j.jacc.2019.01.059 . Lau GT, Tan HC, Kritharides L. Type of liver dysfunction in heart failure and its relation to the severity of tricuspid regurgitation. Am J Cardiol. 2002;90(12):1405–9. doi: 10.1016/s0002-9149(02)02886-2 . Drazner MH, Rame JE, Stevenson LW, Dries DL. Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure. N Engl J Med. 2001;345(8):574–81. doi: 10.1056/NEJMoa010641 . Goncalvesová E. Pečeň pri srdcovom zlyhávaní [Liver in heart failure]. Vnitr Lek . 2014;60:298–303 Poelzl G, Ess M, Mussner-Seeber C, Pachinger O, Frick M, et al. Liver dysfunction in chronic heart failure: prevalence, characteristics and prognostic significance. Eur J Clin Invest. 2012;42(2):153–63. doi: 10.1111/j.1365-2362.2011.02573.x . Sun PY, Jiang X, Gomberg-Maitland M, Zhao QH, He J, et al. Prolonged QRS duration: a new predictor of adverse outcome in idiopathic pulmonary arterial hypertension. Chest. 2012;141(2):374–380. doi: 10.1378/chest.10-3331 . Shenkman HJ, Pampati V, Khandelwal AK, McKinnon J, Nori D, et al. Congestive heart failure and QRS duration: establishing prognosis study. Chest. 2002;122(2):528–34. doi: 10.1378/chest.122.2.528 . Omote K, Sorimachi H, Obokata M, Reddy YNV, Verbrugge FH, et al. Pulmonary vascular disease in pulmonary hypertension due to left heart disease: pathophysiologic implications. Eur Heart J. 2022;43(36):3417–3431. doi: 10.1093/eurheartj/ehac184 . Moraes DL, Colucci WS, Givertz MM. Secondary pulmonary hypertension in chronic heart failure: the role of the endothelium in pathophysiology and management. Circulation. 2000;102(14):1718–23. doi: 10.1161/01.cir.102.14.1718 . Marti CN, Gheorghiade M, Kalogeropoulos AP, Georgiopoulou VV, Quyyumi AA, et al. Endothelial dysfunction, arterial stiffness, and heart failure. J Am Coll Cardiol. 2012;60(16):1455–69. doi: 10.1016/j.jacc.2011.11.082 . Khush KK, Tasissa G, Butler J, McGlothlin D, De Marco T; ESCAPE Investigators. Effect of pulmonary hypertension on clinical outcomes in advanced heart failure: analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) database. Am Heart J. 2009;157(6):1026–34. doi: 10.1016/j.ahj.2009.02.022 . Additional Declarations No competing interests reported. Supplementary Files grafika.pptx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 30 Apr, 2026 Reviews received at journal 30 Apr, 2026 Reviewers agreed at journal 19 Apr, 2026 Reviews received at journal 18 Apr, 2026 Reviewers agreed at journal 17 Apr, 2026 Reviewers agreed at journal 15 Apr, 2026 Reviewers agreed at journal 14 Apr, 2026 Reviewers invited by journal 13 Apr, 2026 Editor assigned by journal 13 Apr, 2026 Submission checks completed at journal 13 Apr, 2026 First submitted to journal 10 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9382853","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":626085778,"identity":"d8308c0a-7000-454f-9158-4c4bdf0db36f","order_by":0,"name":"Samuel Vysočanský","email":"data:image/png;base64,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","orcid":"","institution":"Comenius University Bratislava, Faculty of Medicine, Department of Cardiology, National Institute of Cardiovascular Diseases","correspondingAuthor":true,"prefix":"","firstName":"Samuel","middleName":"","lastName":"Vysočanský","suffix":""},{"id":626085779,"identity":"a7cda68f-fd32-4d2e-97ad-0ef12080a7fe","order_by":1,"name":"Milan Luknár","email":"","orcid":"","institution":"Comenius University Bratislava, Faculty of Medicine, Department of Cardiology, National Institute of Cardiovascular Diseases","correspondingAuthor":false,"prefix":"","firstName":"Milan","middleName":"","lastName":"Luknár","suffix":""},{"id":626085780,"identity":"a23c5b1f-81f4-4d5e-808b-f16930afaf45","order_by":2,"name":"Peter Lesný","email":"","orcid":"","institution":"Comenius University Bratislava, Faculty of Medicine, Department of Cardiology, National Institute of Cardiovascular Diseases","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Lesný","suffix":""},{"id":626085781,"identity":"88b11e38-b06f-4722-a99d-b3e79b6c494b","order_by":3,"name":"Marcela Danková","email":"","orcid":"","institution":"Comenius University Bratislava, Faculty of Medicine, Department of Cardiology, National Institute of Cardiovascular Diseases","correspondingAuthor":false,"prefix":"","firstName":"Marcela","middleName":"","lastName":"Danková","suffix":""},{"id":626085782,"identity":"05f35b78-28a4-4efe-aed6-c8cfbf6c19a3","order_by":4,"name":"Anton Dlesk","email":"","orcid":"","institution":"Comenius University Bratislava, Faculty of Medicine, Department of Cardiology, National Institute of Cardiovascular Diseases","correspondingAuthor":false,"prefix":"","firstName":"Anton","middleName":"","lastName":"Dlesk","suffix":""},{"id":626085784,"identity":"abfe971c-e1ab-428b-a967-db0b2be820c9","order_by":5,"name":"Lucia Mrózová","email":"","orcid":"","institution":"Caldera s.r.o","correspondingAuthor":false,"prefix":"","firstName":"Lucia","middleName":"","lastName":"Mrózová","suffix":""},{"id":626085785,"identity":"59e6390d-8617-42bf-aad5-d6acd71c5558","order_by":6,"name":"Eva Goncalvesová","email":"","orcid":"","institution":"Comenius University Bratislava, Faculty of Medicine, Department of Cardiology, National Institute of Cardiovascular Diseases","correspondingAuthor":false,"prefix":"","firstName":"Eva","middleName":"","lastName":"Goncalvesová","suffix":""}],"badges":[],"createdAt":"2026-04-10 20:09:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9382853/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9382853/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107489050,"identity":"604f80d7-1bb4-48a6-8630-8683fa274587","added_by":"auto","created_at":"2026-04-22 02:46:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":73745,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of patients without PH or with PH and IPC PH/CPC PH phenotype according to the new definition compared to the definition from 2015 ESC PH guidelines.\u003c/p\u003e\n\u003cp\u003eESC, European Society of Cardiology, CPC PH, combined pre- and post-capillary pulmonary hypertension, IPC PH, isolated post-capillary pulmonary hypertension, PH, pulmonary hypertension\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-9382853/v1/ae3ab28b8b1d67c5c3fee0ea.png"},{"id":107489097,"identity":"6d596588-e081-44f4-8ef0-190b6edb9fa3","added_by":"auto","created_at":"2026-04-22 02:46:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":333132,"visible":true,"origin":"","legend":"\u003cp\u003e“Kaplan–Meier survival curves considering the presence of pulmonary hypertension”\u003c/p\u003e\n\u003cp\u003ePH, pulmonary hypertension\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-9382853/v1/00e92958ee836313a944ada6.png"},{"id":107448845,"identity":"11b1a46b-bdb9-4523-8f2a-71e5248dd095","added_by":"auto","created_at":"2026-04-21 14:59:44","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":319727,"visible":true,"origin":"","legend":"\u003cp\u003e“Kaplan–Meier survival curves considering the phenotype of post-capillary PH\u003c/p\u003e\n\u003cp\u003eCPC PH, combined pre- and post-capillary pulmonary hypertension, IPC PH, isolated post-capillary pulmonary hypertension, PH – pulmonary hypertension\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-9382853/v1/67421adadbd613b0898ce589.png"},{"id":108803464,"identity":"684a3555-9a09-4352-998d-6af015691e15","added_by":"auto","created_at":"2026-05-08 14:55:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":946035,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9382853/v1/000f56c5-b202-42c7-afa4-026395d90df6.pdf"},{"id":107448843,"identity":"bdb2b26b-4a12-4801-8ef5-ceda7eec21bc","added_by":"auto","created_at":"2026-04-21 14:59:44","extension":"pptx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1129767,"visible":true,"origin":"","legend":"","description":"","filename":"grafika.pptx","url":"https://assets-eu.researchsquare.com/files/rs-9382853/v1/f40b49926a5450a188570146.pptx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pulmonary hypertension in advanced heart failure with reduced ejection fraction. What are the consequences of the new definition?","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePost-capillary PH, a common component of the HF syndrome, results from passive transmission of elevated left ventricle filling pressure [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. 2022 ESC PH guidelines redefined PH as mean pulmonary artery pressure (mPAP)\u0026thinsp;\u0026gt;\u0026thinsp;20 mm Hg [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Post-capillary PH reamins being defined by pulmonary artery wedge pressure (PAWP)\u0026thinsp;\u0026gt;\u0026thinsp;15 mm Hg, while pulmonary vascular resistance (PVR)\u0026thinsp;\u0026gt;\u0026thinsp;2 WU defines a combined pre- and post-capillary (CPC) phenotype [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Pre-capillary vasculature remodelling in CPC PH, referred to as pulmonary vascular disease (PVD), contributes to right ventricular dysfunction and is associated with adverse outcomes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe reported prevalence of PH in HFrEF varies widely depending on patient characteristics and diagnostic modality, ranging from 35\u0026ndash;48% in echocardiographic studies [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] to 46\u0026ndash;72% in invasive right-heart catheterization (RHC) studies [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, these data largely reflect patients with stable or de novo HFrEF. Data regarding the prevalence of PH in advanced HFrEF are scarce.\u003c/p\u003e \u003cp\u003ePrevious RHC-based studies were conducted using earlier PH definitions. The impact of the 2022 classification on PH prevalence, phenotypes, and associated factors in advanced HFrEF remains unclear. This study aims to analyze the prevalence, characteristics, predictors of PH, its phenotypes and survival in patients with advanced chronic HFrEF according to the recent definition [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] in current era.\u003c/p\u003e"},{"header":"2. Patients and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study design\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed patients hospitalized between 2017 and 2020 for advanced HFrEF, regardless of disease duration. The main inclusion criterion was left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF)\u0026thinsp;\u0026lt;\u0026thinsp;40%. Exclusion criteria were as follows: age\u0026thinsp;\u0026lt;\u0026thinsp;18 years, patients with an LVAD, patients with severe lung disease (total lung capacity\u0026thinsp;\u0026lt;\u0026thinsp;60% of predicted, forced expiratory volume\u0026thinsp;\u0026lt;\u0026thinsp;60% of predicted, the need for long-term oxygen therapy or PaO2\u0026thinsp;\u0026lt;\u0026thinsp;60 mmHg). All patients underwent RHC. Selected clinical, anthropometric, laboratory, electrocardiographic, echocardiographic, and hemodynamic data were extracted from the medical records maintained in a standard protocol manner [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Right heart catheterization methodology\u003c/h2\u003e \u003cp\u003eRight heart catheterization (RHC) was performed using a Swan-Ganz thermodilution catheter under standard conditions within 24 hours of echocardiography and peripheral blood sampling. In patients with congestive signs, RHC was performed after achieving euvolemia.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Definitions\u003c/h2\u003e \u003cp\u003e Patients were classified into one of three groups according to the ESC guidelines (2) - patients in whom invasive testing did not prove the presence of PH, patients with IPC PH and CPC PH respectively. The IPC PH was defined as mPAP\u0026thinsp;\u0026gt;\u0026thinsp;20 mm Hg, PAWP\u0026thinsp;\u0026gt;\u0026thinsp;15 mm Hg, PVR \u0026le; 2 WU. If PVR was \u0026gt;\u0026thinsp;2 WU, patients were classified as CPC PH.\u003c/p\u003e \u003cp\u003eFor survival analysis, 2-year survival was assessed, with the endpoint defined as either mechanical circulatory support implantation or all-cause mortality. Urgent heart transplantation is not available in our region and was therefore not considered a relevant endpoint.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Statistics\u003c/h2\u003e \u003cp\u003eContinuous variables are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and categorical variables as n (%). Group differences were assessed using Student\u0026rsquo;s t-test or chi-square test. Logistic regression was used to identify variables associated with PH phenotypes, presented as odds ratios (OR). Survival analysis was performed using Kaplan\u0026ndash;Meier estimates and Cox proportional hazards regression, with results expressed as hazard ratios (HR). A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. The predictive performance of non-invasive sPAP for CPC PH was assessed using receiver operating characteristic (ROC) curves and the area under the curve (AUC).\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Baseline characteristics\u003c/h2\u003e \u003cp\u003eA total of 175 patients were enrolled (39 women). The predominant etiology was dilated cardiomyopathy, followed by ischemic heart disease. Less frequent causes included hypertensive heart disease, burnt-out hypertrophic cardiomyopathy, non-compaction cardiomyopathy, chronic myocarditis, and valvular heart disease. The median age was 54 years, and mean LVEF was 21.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7%. The mean duration from HF diagnosis to RHC was 112\u0026thinsp;\u0026plusmn;\u0026thinsp;103 months. Most patients were in NYHA class III (124 patients) or class IV (40 patients). Baseline clinical characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNumber of pts\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMen (n/%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136/78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eHF etiology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDCMP (n/%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCAD (n/%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther (n/%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDuration of the HF (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112\u0026thinsp;\u0026plusmn;\u0026thinsp;103\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLVEF (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNYHA I/II/III/IV (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/11/124/40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eCAD, coronary artery disease, DCMP, dilated cardiomyopathy, HF, heart failure, LVEF, left ventricle ejection fraction, NYHA, New York Heart Association\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Non-invasive and invasive characteristics\u003c/h2\u003e \u003cp\u003ePost-capillary PH was present in 83% of patients, with 24% of them classified as IPC PH and 76% as CPC PH (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients with PH had longer HF duration, lower blood pressure. Echocardiography revealed more advanced cardiac remodeling, including larger left atrium and right ventricle with impaired systolic function. PH patients were more likely to have moderate or severe mitral regurgitation (MR), while there was no significant difference in either the presence or the severity of tricuspid regurgitation (TR), but a trend could be observed (p\u0026thinsp;=\u0026thinsp;0.06).\u003c/p\u003e \u003cp\u003ePH was also associated with a higher prevalence of atrial fibrillation and renal insufficiency (KDIGO G2\u0026ndash;G5, defined as eGFR\u0026thinsp;\u0026lt;\u0026thinsp;90 mL/min/1.73 m\u0026sup2;). Among laboratory markers, PH was linked to lower serum sodium and higher concentrations of NT-proBNP, uric acid (UA), and liver enzymes gamma-glutamyl transferase (GMT), serum bilirubin (bil). The only electrocardiographic parameter showing significant difference was a wider QRS complex in PH group. Lung function parameters (FEV₁, FVC, FEV₁/FVC) were comparable between groups. Hemodynamic parameters were not compared between PH and non-PH patients, as differences in pulmonary pressures inherently define PH.\u003c/p\u003e \u003cp\u003eCPC PH patients were older, had lower exercise capacity, and a higher prevalence of renal insufficiency and type 2 diabetes. Among non-invasive parameters, only higher sPAP differentiated CPC PH from IPC PH. Hemodynamic impairment was more pronounced in CPC PH, while RAP did not differ between groups (10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2 vs 11.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4 mm Hg; p\u0026thinsp;=\u0026thinsp;0.37). Detailed data are provided in Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDifferences in observed parameters between patients with and without PH\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePH \u0026ndash; (mPAP\u0026thinsp;\u0026le;\u0026thinsp;20 mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePH + (mPAP\u0026thinsp;\u0026gt;\u0026thinsp;20 mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"11\" rowspan=\"12\"\u003e \u003cp\u003eClinical parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDuration of disease (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46\u0026thinsp;\u0026plusmn;\u0026thinsp;55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81\u0026thinsp;\u0026plusmn;\u0026thinsp;67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.590\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex (M/F) (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72/28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79/21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.453/0.414\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120\u0026thinsp;\u0026plusmn;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e108\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHeart rate (min\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85\u0026thinsp;\u0026plusmn;\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.639\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.533\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEtiology (CAD/%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.319\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEtiology (DCMP/%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.289\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNYHA II/III/IV (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14/72/14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5/71/25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.112/0.156/0.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6-MWD (m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e351\u0026thinsp;\u0026plusmn;\u0026thinsp;143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e402\u0026thinsp;\u0026plusmn;\u0026thinsp;117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003eEchocardiographic parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLVEF (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLVEDD (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLA (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMR (moderate - severe) (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTR (moderate - severe) (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRV (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTAPSE (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"13\" rowspan=\"14\"\u003e \u003cp\u003eLaboratory parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUA (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e382\u0026thinsp;\u0026plusmn;\u0026thinsp;103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e469\u0026thinsp;\u0026plusmn;\u0026thinsp;141\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNa (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e141\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e140\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNT-proBNP (ug/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1976\u0026thinsp;\u0026plusmn;\u0026thinsp;2376\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4565\u0026thinsp;\u0026plusmn;\u0026thinsp;4087\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCreatinine (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e123\u0026thinsp;\u0026plusmn;\u0026thinsp;147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101\u0026thinsp;\u0026plusmn;\u0026thinsp;29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.422\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrea (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.182\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCKD-EPI (mL/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.980\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALP (ukat/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAST (ukat/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.437\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALT (ukat/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;5.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.534\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGMT (ukat/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBil (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFe (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.863\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFerritin (ug/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e151\u0026thinsp;\u0026plusmn;\u0026thinsp;125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e144\u0026thinsp;\u0026plusmn;\u0026thinsp;139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.816\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHemoglobin (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e140\u0026thinsp;\u0026plusmn;\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e136\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.253\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eECG parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePQ (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.168\u0026thinsp;\u0026plusmn;\u0026thinsp;0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.184\u0026thinsp;\u0026plusmn;\u0026thinsp;0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQRS (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.098\u0026thinsp;\u0026plusmn;\u0026thinsp;0.023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.117\u0026thinsp;\u0026plusmn;\u0026thinsp;0.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLBBB (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.341\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eComorbidities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypertension (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDyslipidaemia (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.263\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiabetes mellitus (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.923\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAtrial fibrillation (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRenal insuficiency (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePulmonary\u003c/p\u003e \u003cp\u003efunction test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFEV1 (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87\u0026thinsp;\u0026plusmn;\u0026thinsp;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.059\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFVC (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.084\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFEV1/FVC (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.996\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e \u003cp\u003eHemodynamic parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003esPAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51.0\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003edPAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emPAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePAWP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTPG (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDPG (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.731\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePVR (WU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCO (l/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCI (l/min/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eALP, alkaline phosphatase, ALT, alanine aminotransferase, AST, aspartate aminotransferase, Bil, bilirubin, BMI, body mass index, CAD, coronary artery disease, CI, cardiac index, CKD-EPI, chronic kidney disease epidemiology collaboration, CO, cardiac output, DBP, diastolic blood pressure, DCMP, dilated cardiomyopathy, DPAP, diastolic pulmonary artery pressure, DPG, diastolic pressure gradient, Fe, iron, FEV1, forced expiratory volume, FVC, functional vital capacity, GMT, gamma- glutamyl transferase, LA, left atrium, LBBB, left bundle brunch block, LVEDD, left ventricle end-diastolic diameter, LVEF, left ventricle ejection fraction, MPAP, mean pulmonary artery pressure, MR, mitral regurgitation, NT-proBNP, N-terminal pro b-type natriuretic peptide, PAWP, pulmonary artery wedge pressure, PVR, pulmonary vascular resistance, RAP, right atrial pressure, RBBB, right bundle brunch block, RV, right ventricle, SPAP, systolic pulmonary artery pressure, SPB, systolic blood pressure, TAPSE, tricuspid annular plane systolic excursion, TPG, transpulmonary pressure gradient, TR, tricuspid regurgitation, UA, uric acid\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDifferences in observed parameters between IPC PH and CPC PH patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIPC PH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCPC PH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"11\" rowspan=\"12\"\u003e \u003cp\u003eClinical parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDuration of disease (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73\u0026thinsp;\u0026plusmn;\u0026thinsp;63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83\u0026thinsp;\u0026plusmn;\u0026thinsp;69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.449\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex (M/F) (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74/26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80/20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.578/0.446\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e108\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.763\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDBP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.759\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHeart rate (min\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.950\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.547\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.778\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEtiology (CAD/%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEtiology (DCMP/%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNYHA II/III/IV (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/77/20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5/68/26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.592/0.478/0.378\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6-MWD (m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e439\u0026thinsp;\u0026plusmn;\u0026thinsp;74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e390\u0026thinsp;\u0026plusmn;\u0026thinsp;126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003eEchocardiographic parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLVEF (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLVEDD (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.373\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLA (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.205\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMR (moderate \u0026ndash; severe) (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.515\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTR (moderate - severe) (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRV (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTAPSE (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.576\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003esPAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTAPSE/sPAP (mm/mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.079\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"13\" rowspan=\"14\"\u003e \u003cp\u003eLaboratory parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUA (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e474\u0026thinsp;\u0026plusmn;\u0026thinsp;139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e467\u0026thinsp;\u0026plusmn;\u0026thinsp;142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.816\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNa (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e140\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNT-proBNP (ug/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3823\u0026thinsp;\u0026plusmn;\u0026thinsp;2560\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4803\u0026thinsp;\u0026plusmn;\u0026thinsp;4452\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCreatinine (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97\u0026thinsp;\u0026plusmn;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e102\u0026thinsp;\u0026plusmn;\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.360\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrea (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCKD-EPI (mL/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALP (ukat/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.426\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAST (ukat/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.801\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALT (ukat/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;6.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.471\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGMT (ukat/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.09\u0026thinsp;\u0026plusmn;\u0026thinsp;2.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.443\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBil (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.524\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFe (umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.377\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFerritin (ug/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e170\u0026thinsp;\u0026plusmn;\u0026thinsp;190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e135\u0026thinsp;\u0026plusmn;\u0026thinsp;116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.258\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHemoglobin (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e135\u0026thinsp;\u0026plusmn;\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e136\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.833\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eECG parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePQ (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.175\u0026thinsp;\u0026plusmn;\u0026thinsp;0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.186\u0026thinsp;\u0026plusmn;\u0026thinsp;0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.238\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQRS (ms)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.109\u0026thinsp;\u0026plusmn;\u0026thinsp;0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.120\u0026thinsp;\u0026plusmn;\u0026thinsp;0.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLBBB (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.304\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eComorbidities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypertension (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.288\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDyslipidaemia (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.600\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiabetes mellitus (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAtrial fibrillation (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.850\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRenal insufficiency (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePulmonary\u003c/p\u003e \u003cp\u003efunction test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFEV1 (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.518\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFVC (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.293\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFEV1/FVC (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.981\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e \u003cp\u003eHemodynamic parameters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003esPAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55.0\u0026thinsp;\u0026plusmn;\u0026thinsp;13.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003edPAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emPAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePAWP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTPG (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDPG (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePVR (WU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCO (l/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCI (l/min/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eALP, alkaline phosphatase, ALT, alanine aminotransferase, AST, aspartate aminotransferase, Bil, bilirubin, BMI, body mass index, CAD, coronary artery disease, CI, cardiac index, CKD-EPI, chronic kidney disease epidemiology collaboration, CO, cardiac output, DBP, diastolic blood pressure, DCMP, dilated cardiomyopathy, DPAP, diastolic pulmonary artery pressure, DPG, diastolic pressure gradient, Fe, iron, FEV1, forced expiratory volume, FVC, functional vital capacity, GMT, gamma-glutamyl transferase, LA, left atrium, LBBB, left bundle brunch block, LVEDD, left ventricle end-diastolic diameter, LVEF, left ventricle ejection fraction, MPAP, mean pulmonary artery pressure, MR, mitral regurgitation, NT-proBNP, N-terminal pro b-type natriuretic peptide, PAWP, pulmonary artery wedge pressure, PVR, pulmonary vascular resistance, RAP, right atrial pressure, RBBB, right bundle brunch block, RV, right ventricle, SPAP, systolic pulmonary artery pressure, SPB, systolic blood pressure, TAPSE, tricuspid annular plane systolic excursion, TPG, transpulmonary pressure gradient, TR, tricuspid regurgitation, UA, uric acid\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Predictors of PH and CPC PH\u003c/h2\u003e \u003cp\u003eIn univariate analysis, multiple clinical, echocardiographic, and laboratory variables were associated with PH, all of them being summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. sPAP was excluded as it represents a surrogate marker of PH.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVariables associated with the presence of PH\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnivariate Odds Ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMultivariate Odds Ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.060 (1.012\u0026ndash;1.110)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.044 (0.908\u0026ndash;1.199)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.547\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.079 (0.677\u0026ndash;0.896)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.910 (0.660\u0026ndash;1.254)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.603 (0.499\u0026ndash;0.810)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.846 (0.395\u0026ndash;1.812)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.667\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.136 (1.059\u0026ndash;1.218)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.158 (1.020\u0026ndash;1.315)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMR (moderate/severe)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.593 (1.520-13.883)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.600 (0.339\u0026ndash;38.178)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.288\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.083 (1.021\u0026ndash;1.148)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.890 (0.774\u0026ndash;1.022)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAPSE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.850 (0.773\u0026ndash;0.935)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.811 (0.674\u0026ndash;0.976)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.887 (0.822\u0026ndash;0.956)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.879 (0.704\u0026ndash;1.098)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.256\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.060 (1.021\u0026ndash;1.101)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.065 (0.961\u0026ndash;1.181)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNT-proBNP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.047 (1.018\u0026ndash;1.076)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.879 (0.982\u0026ndash;1.074)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.246\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGMT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.129 (1.044\u0026ndash;1.222)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.062 (0.925\u0026ndash;1.219)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.393\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.086 (1.024\u0026ndash;1.151)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.959 (0.831\u0026ndash;1.107)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.565\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.423 (1.134\u0026ndash;1.784)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.019 (0.648\u0026ndash;1.602)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.935\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eBil, bilirubin, CI, cardiac index, GMT, gamma-glutamyl transferase, LA, left atrium, LVEF, left ventricle ejection fraction, MR, mitral regurgitation, NT-proBNP, N-terminal pro b-type natriuretic peptide, RV, right ventricle, SPB, systolic blood pressure, TAPSE, tricuspid annular plane systolic excursion, UA, uric acid\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVariables associated with the presence of CPC PH\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnivariate Odds Ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMultivariate Odds Ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.055 (1.020\u0026ndash;1.092)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.045 (1.000-1.091)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal insufficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.000 (1.076\u0026ndash;8.367)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.254 (0.484\u0026ndash;10.497)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.300\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.569 (1.170-10.891)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.940 (0.217\u0026ndash;4.066)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.934\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esPAP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.075 (1.035\u0026ndash;1.118)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.064 (1.018\u0026ndash;1.111)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePAWP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.179 (1.087\u0026ndash;1.279)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.131 (1.015\u0026ndash;1.261)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ePAWP, pulmonary artery wedge pressure SPAP, systolic pulmonary artery pressure\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eCPC PH, combined pre- and post-capillary pulmonary hypertension, IPC PH, isolated post-capillary pulmonary hypertension, PH \u0026ndash; pulmonary hypertension\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAfter multivariate adjustment, only left atrial diameter and TAPSE remained independent predictors of PH. For the CPC PH phenotype, age and sPAP were the only independent non-invasive predictors, while PAWP was the only independent invasive predictor. For differentiating post-capillary PH phenotypes, an sPAP value\u0026thinsp;\u0026gt;\u0026thinsp;55 mm Hg obtained by echocardiography identified CPC PH with moderate accuracy (C-statistic 0.76; sensitivity 47%; specificity 81%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Prognostic value of the new PH definiton\u003c/h2\u003e \u003cp\u003eFor survival analysis, patients who underwent non-urgent heart transplantation (HTx) were excluded, as many of them might have had advanced yet relatively stable HFrEF course. In total, 42 patients received HTx (11 with IPC PH, 26 with CPC PH and 5 without PH). The median interval between the first RHC and HTx was 1006\u0026thinsp;\u0026plusmn;\u0026thinsp;215 days in patients without PH, 397\u0026thinsp;\u0026plusmn;\u0026thinsp;301 days in those with IPC PH and 183\u0026thinsp;\u0026plusmn;\u0026thinsp;128 days in the CPC PH group.\u003c/p\u003e \u003cp\u003eThe primary endpoint was a composite of all-cause mortality, urgent listing for HTx, or urgent mechanical circulatory support (MCS) implantation. During follow-up, 59 patients died, 34 required MCS implantation, and 2 were listed as urgent HTx candidates. The median time from the reference RHC to the endpoint was 775\u0026thinsp;\u0026plusmn;\u0026thinsp;710 days.\u003c/p\u003e \u003cp\u003eSurvival according to PH presence is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Two-year survival was assessed from the reference RHC. One-year mortality was 36% in patients with PH and 3% in patients without PH; two-year mortality was 53% and 12%, respectively. A significant difference in survival was also observed across PH phenotypes (p\u0026thinsp;=\u0026thinsp;0.039) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In the IPC PH group, one-year mortality was 21% compared with 38% in the CPC PH group. After two years, mortality increased to 37% in IPC PH and 62% in CPC PH.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e4.1. PH prevalence according to the new definition\u003c/h2\u003e \u003cp\u003eApplying the new definition, PH was present in 83% of patients, compared with 77% using the previous mPAP\u0026thinsp;\u0026ge;\u0026thinsp;25 mm Hg threshold, indicating minimal impact on overall prevalence. The slightly lower prevalence of PH, 77% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], resp. 68% [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] in patients with HF according to the findings of other authors is probably related to less advanced HF in the populations studied and not to the definition of PH being valid at the time. Using the lower mPAP as the PH defining criterion, PH was present in 62% [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and 64% [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] of patients with less advanced stages of HFrEF. A recent multicenter study reported a modest increase in PH prevalence with the updated criteria, although comparison is limited by a high proportion of HFpEF patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Overall, these findings suggest that PH prevalence in HF is driven primarily by disease severity and patient characteristics rather than the specific mPAP cutoff. Our results further support that PH represents a common feature of advanced HFrEF even in the modern therapeutic era of HF.\u003c/p\u003e \u003cp\u003eLowering the PVR threshold for CPC PH represents a more impactful change. This modification was largely based on data showing increasing risk of death and hospitalization from PVR\u0026thinsp;\u0026ge;\u0026thinsp;2.2 WU, although this association was less pronounced in post-capillary PH [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, it can be debated whether a different, higher, PVR cut-off value should be chosen to express clinically significant PVD in patients with post-capillary PH. In our cohort, applying the new criteria led to a disproportionate increase in CPC PH prevalence (76%), compared with 46% using the 2015 definition. Similarly, Fauvel et al. reported a disproportionate rise in CPC PH prevalence from 42% to 67% when adopting the lowered PVR threshold.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.2. Predictors of PH\u003c/h2\u003e \u003cp\u003eThe high prevalence of PH in our cohort reflects the advanced stage of HFrEF [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], with up to 94% of patients being in NYHA classIII/IV. The presence of PH was associated with a prognostically unfavourable patient profile - lower systolic blood pressure, lower LVEF, higher natriuretic peptide and UA levels [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Several studies, including meta-analyses, have shown that elevated serum UA levels predict increased risk of death and hospitalizations for PH [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and inversely correlate with CO [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The impact of MR on the development of PH in the context of HFrEF is well known [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], as confirmed by our results showing the association of PH with moderate and severe MR. Moderate or severe MR has been shown to be an independent predictor of PH in the group of patients with advanced HFrEF, along with TR and the duration of disease [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Right ventricular (RV) dysfunction represents a downstream consequence of PH, potentially affect peripheral organ functions [\u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. RV dysfunction was more pronounced in PH affected patients, accompanied by a cholestatic laboratory profile consistent with advanced right-sided HF. Finally, QRS prolongation was associated with PH, likely reflecting more advanced myocardial remodeling and its known link to worse prognosis [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.3. Predictors of CPC PH\u003c/h2\u003e \u003cp\u003eDistinguishing IPC PH from CPC PH using clinical and non-invasive parameters remains challenging. CPC PH was more frequent in older patients and those with diabetes and renal insufficiency. The association of an older age and renal insufficiency with impaired pulmonary vasculature previously described in HFpEF patients [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] likely reflects proinflammatory state leading to the endothelial dysfunction rather than pulmonary disease [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Consistently, spirometric parameters did not differ between groups, supporting a limited role of primary lung pathology. Among non-invasive measures, only sPAP differentiated PH phenotypes, with values\u0026thinsp;\u0026gt;\u0026thinsp;55 mm Hg identifying CPC PH with acceptable accuracy. This finding may facilitate non-invasive phenotyping and patient selection in studies targeting PVD as therapeutic target in HFrEF.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e4.4. Outcomes according to the hemodynamic profile\u003c/h2\u003e \u003cp\u003ePH in HF is a strong determinant of mortality irrespective of LVEF. In our cohort, its adverse prognostic impact persisted despite the lower mPAP threshold, with CPC PH consistently identifying a subgroup at substantially higher risk compared with IPC PH. These results suggest that the CPC PH phenotype may warrant consideration as an additional factor when prioritizing patients on the heart transplant waiting list. To our knowledge, this is the first study to evaluate survival in patients with advanced HF and PH using the modified hemodynamic classification of post-capillary PH. Evidence regarding outcomes in patients with advanced HFrEF and CpcPH remains scarce. A subanalysis of the ESCAPE trial showed no difference in mortality between patients with advanced HFrEF and CpcPH\u0026mdash;defined by PVR\u0026thinsp;\u0026ge;\u0026thinsp;3 WU\u0026mdash;and those with PH and PVR\u0026thinsp;\u0026lt;\u0026thinsp;3 WU [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]; however, the follow-up period was limited to only 6 months. More recent data examining the impact of the updated PH definition across HF populations, regardless of LVEF, demonstrated significantly worse outcomes in CPC PH even when applying a lower PVR threshold [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], consistent with our findings.Taken together, these findings suggest that the revised PH definition not only refines hemodynamic classification but also enhances prognostic discrimination, particularly by identifying a high-risk CPC PH phenotype across the HF spectrum.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThe new PH definition has minimal impact on overall PH prevalence in HF but leads to a marked increase in CPC PH, expanding its heterogeneity, which may affect design of future clinical trials targeting the pre-capillary component of PH, such as studies evaluating PAH-specific therapies in post-capillary PH. Non-invasive identification of PVD will therefore be challenging, although sPAP\u0026thinsp;\u0026gt;\u0026thinsp;55 mm Hg emerged as a useful discriminator in advanced HFrEF. However, the revised definition retains prognostic value by identifying a high-risk CPC PH phenotype, with potential implications for patient monitoring and therapeutic decision-making.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e All authors have participated in the work and have reviewed and agree with the content of the article. None of the article contents are under consideration for publication in any other journal or have been published in any journal. The authors have no relevant financial or non-financial interests to declare associated with the topic of this manuscript.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical Approval\u003c/strong\u003e \u003cp\u003e This study protocol was approved by the Ethics Committee of the National Institute of Cardiovascular Diseases, Bratislava, Slovakia, on December 15, 2020. The study was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding sources\u003c/h2\u003e \u003cp\u003eThere are no funding sources to declare.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eSV and EG wrote the main manuscript text and prepared all figures. ML, PL, MD, SV performed right-heart catheterisations. AD performed echocardiography examinations. LM was responsible for the statistics. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGuha A, Amione-Guerra J, Park MH. Epidemiology of Pulmonary Hypertension in Left Heart Disease. Prog Cardiovasc Dis. 2016 Jul-Aug;59(1):3\u0026ndash;10. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.pcad.2016.07.001\u003c/span\u003e\u003cspan address=\"10.1016/j.pcad.2016.07.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHumbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, et al.; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618\u0026ndash;3731. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehac237\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehac237\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Erratum in: Eur Heart J. 2023;44(15):1312. doi: 10.1093/eurheartj/ehad005.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009;34(4):888\u0026ndash;94. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1183/09031936.00145608\u003c/span\u003e\u003cspan address=\"10.1183/09031936.00145608\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeitouni M, Morlon Q, Silvain J, Procopi N, Guedeney P, et al. Implication of the new definition of pulmonary hypertension in patients evaluated for heart transplantation. Int J Cardiol. 2023;384:18\u0026ndash;24. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ijcard.2023.04.048\u003c/span\u003e\u003cspan address=\"10.1016/j.ijcard.2023.04.048\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiller WL, Mahoney DW, Michelena HI, Pislaru SV, Topilsky Y, et al. Contribution of ventricular diastolic dysfunction to pulmonary hypertension complicating chronic systolic heart failure. JACC Cardiovasc Imaging. 2011;4(9):946\u0026ndash;54. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jcmg.2011.06.017\u003c/span\u003e\u003cspan address=\"10.1016/j.jcmg.2011.06.017\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmei\u0026szlig;er A, Rauwolf T, Groscheck T, Fischbach K, Kropf S, et al. Predictors and prognosis of right ventricular function in pulmonary hypertension due to heart failure with reduced ejection fraction. ESC Heart Fail. 2021;8(4):2968\u0026ndash;2981. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ehf2.13386\u003c/span\u003e\u003cspan address=\"10.1002/ehf2.13386\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenfari G, Antoine C, Miller WL, Thapa P, Topilsky Y, et al. Excess Mortality Associated With Functional Tricuspid Regurgitation Complicating Heart Failure With Reduced Ejection Fraction. Circulation. 2019;140(3):196\u0026ndash;206. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/CIRCULATIONAHA.118.038946\u003c/span\u003e\u003cspan address=\"10.1161/CIRCULATIONAHA.118.038946\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSzwejkowski BR, Elder DH, Shearer F, Jack D, Choy AM, et al. Pulmonary hypertension predicts all-cause mortality in patients with heart failure: a retrospective cohort study. Eur J Heart Fail. 2012;14(2):162\u0026ndash;7. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurjhf/hfr159\u003c/span\u003e\u003cspan address=\"10.1093/eurjhf/hfr159\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCappola TP, Felker GM, Kao WH, Hare JM, Baughman KL, et al. Pulmonary hypertension and risk of death in cardiomyopathy: patients with myocarditis are at higher risk. Circulation. 2002;105(14):1663\u0026ndash;8. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/01.cir.0000013771.30198.82\u003c/span\u003e\u003cspan address=\"10.1161/01.cir.0000013771.30198.82\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiller WL, Grill DE, Borlaug BA. Clinical features, hemodynamics, and outcomes of pulmonary hypertension due to chronic heart failure with reduced ejection fraction: pulmonary hypertension and heart failure. JACC Heart Fail. 2013;1(4):290\u0026ndash;299. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jchf.2013.05.001\u003c/span\u003e\u003cspan address=\"10.1016/j.jchf.2013.05.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoncalvesov\u0026aacute; E. 2022. Manu\u0026aacute;l diagnostick\u0026yacute;ch, indikačn\u0026yacute;ch a liečebn\u0026yacute;ch postupov. 6. vydanie. Bratislava: Herba, 2022. 131p. ISBN 978-80-8229-25-0\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGerges M, Gerges C, Pistritto AM, Lang MB, Trip P, et al. Pulmonary Hypertension in Heart Failure. Epidemiology, Right Ventricular Function, and Survival. Am J Respir Crit Care Med. 2015;192(10):1234\u0026ndash;46. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1164/rccm.201503-0529OC\u003c/span\u003e\u003cspan address=\"10.1164/rccm.201503-0529OC\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhio S, Gavazzi A, Campana C, Inserra C, Klersy C, et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol. 2001;37(1):183\u0026ndash;8. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0735-1097(00)01102-5\u003c/span\u003e\u003cspan address=\"10.1016/s0735-1097(00)01102-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIbe T, Wada H, Sakakura K, Ugata Y, Maki H, et al. Combined pre- and post-capillary pulmonary hypertension: The clinical implications for patients with heart failure. PLoS One. 2021;16(3):e0247987. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0247987\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0247987\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFauvel C, Damy T, Berthelot E, Bauer F, Eicher JC, et al. Post-capillary pulmonary hypertension in heart failure: impact of current definition in the PH-HF multicentre study. Eur Heart J. 2024;45(35):3274\u0026ndash;3288. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehae467\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehae467\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaron BA, Brittain EL, Hess E, Waldo SW, Bar\u0026oacute;n AE, et al. Pulmonary vascular resistance and clinical outcomes in patients with pulmonary hypertension: a retrospective cohort study. Lancet Respir Med. 2020;8(9):873\u0026ndash;884. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S2213-2600(20)30317-9\u003c/span\u003e\u003cspan address=\"10.1016/S2213-2600(20)30317-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCrespo-Leiro MG, Metra M, Lund LH, Milicic D, Costanzo MR, et al. Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018;20(11):1505\u0026ndash;1535. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ejhf.1236\u003c/span\u003e\u003cspan address=\"10.1002/ejhf.1236\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMetra M, Dinatolo E, Dasseni N. The New Heart Failure Association Definition of Advanced Heart Failure. Card Fail Rev. 2019;5(1):5\u0026ndash;8. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.15420/cfr.2018.43.1\u003c/span\u003e\u003cspan address=\"10.15420/cfr.2018.43.1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiao L, Guo M, Pan D, Chen P, Chen Z, et al. Serum Uric Acid and Risk of Chronic Heart Failure: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2021;8:785327. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fmed.2021.785327\u003c/span\u003e\u003cspan address=\"10.3389/fmed.2021.785327\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang H, Huang B, Li Y, Huang Y, Li J, et al. Uric acid and risk of heart failure: a systematic review and meta-analysis. Eur J Heart Fail. 2014;16(1):15\u0026ndash;24. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurjhf/hft132\u003c/span\u003e\u003cspan address=\"10.1093/eurjhf/hft132\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmin A, Vakilian F, Maleki M. Serum uric acid levels correlate with filling pressures in systolic heart failure. Congest Heart Fail. 2011 Mar-Apr;17(2):80\u0026ndash;4. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1751-7133.2010.00205.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1751-7133.2010.00205.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeis T, Rossing K, Ersb\u0026oslash;ll MK, Wolsk E, Gustafsson F. Uric acid in advanced heart failure: relation to central haemodynamics and outcome. Open Heart. 2022;9(2):e002092. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/openhrt-2022-002092\u003c/span\u003e\u003cspan address=\"10.1136/openhrt-2022-002092\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGivertz MM, Anstrom KJ, Redfield MM, Deswal A, Haddad H, et al. Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) Study. Circulation. 2015;131(20):1763\u0026ndash;71. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/CIRCULATIONAHA.114.014536\u003c/span\u003e\u003cspan address=\"10.1161/CIRCULATIONAHA.114.014536\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosenhek R, Iung B, Tornos P, Antunes MJ, Prendergast BD, et al. ESC Working Group on Valvular Heart Disease Position Paper: assessing the risk of interventions in patients with valvular heart disease. Eur Heart J. 2012;33(7):822-8, 828a, 828b. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehr061\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehr061\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTorres-Macho J, Delgado-Jim\u0026eacute;nez JF, Sanz-Salvo J, Gonz\u0026aacute;lez-Mansilla A, S\u0026aacute;nchez-S\u0026aacute;nchez V, et al. Predictors of pulmonary hypertension in patients with end-stage heart failure. Congest Heart Fail. 2012 Jul-Aug;18(4):212\u0026ndash;6. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1751-7133.2011.00277.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1751-7133.2011.00277.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomas L, Marwick TH, Popescu BA, Donal E, Badano LP. Left Atrial Structure and Function, and Left Ventricular Diastolic Dysfunction: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(15):1961\u0026ndash;1977. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jacc.2019.01.059\u003c/span\u003e\u003cspan address=\"10.1016/j.jacc.2019.01.059\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLau GT, Tan HC, Kritharides L. Type of liver dysfunction in heart failure and its relation to the severity of tricuspid regurgitation. Am J Cardiol. 2002;90(12):1405\u0026ndash;9. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0002-9149(02)02886-2\u003c/span\u003e\u003cspan address=\"10.1016/s0002-9149(02)02886-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrazner MH, Rame JE, Stevenson LW, Dries DL. Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure. N Engl J Med. 2001;345(8):574\u0026ndash;81. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa010641\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa010641\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoncalvesov\u0026aacute; E. Pečeň pri srdcovom zlyh\u0026aacute;van\u0026iacute; [Liver in heart failure]. \u003cem\u003eVnitr Lek\u003c/em\u003e. 2014;60:298\u0026ndash;303\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePoelzl G, Ess M, Mussner-Seeber C, Pachinger O, Frick M, et al. Liver dysfunction in chronic heart failure: prevalence, characteristics and prognostic significance. Eur J Clin Invest. 2012;42(2):153\u0026ndash;63. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1365-2362.2011.02573.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1365-2362.2011.02573.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun PY, Jiang X, Gomberg-Maitland M, Zhao QH, He J, et al. Prolonged QRS duration: a new predictor of adverse outcome in idiopathic pulmonary arterial hypertension. Chest. 2012;141(2):374\u0026ndash;380. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1378/chest.10-3331\u003c/span\u003e\u003cspan address=\"10.1378/chest.10-3331\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShenkman HJ, Pampati V, Khandelwal AK, McKinnon J, Nori D, et al. Congestive heart failure and QRS duration: establishing prognosis study. Chest. 2002;122(2):528\u0026ndash;34. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1378/chest.122.2.528\u003c/span\u003e\u003cspan address=\"10.1378/chest.122.2.528\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOmote K, Sorimachi H, Obokata M, Reddy YNV, Verbrugge FH, et al. Pulmonary vascular disease in pulmonary hypertension due to left heart disease: pathophysiologic implications. Eur Heart J. 2022;43(36):3417\u0026ndash;3431. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehac184\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehac184\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoraes DL, Colucci WS, Givertz MM. Secondary pulmonary hypertension in chronic heart failure: the role of the endothelium in pathophysiology and management. Circulation. 2000;102(14):1718\u0026ndash;23. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/01.cir.102.14.1718\u003c/span\u003e\u003cspan address=\"10.1161/01.cir.102.14.1718\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarti CN, Gheorghiade M, Kalogeropoulos AP, Georgiopoulou VV, Quyyumi AA, et al. Endothelial dysfunction, arterial stiffness, and heart failure. J Am Coll Cardiol. 2012;60(16):1455\u0026ndash;69. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jacc.2011.11.082\u003c/span\u003e\u003cspan address=\"10.1016/j.jacc.2011.11.082\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhush KK, Tasissa G, Butler J, McGlothlin D, De Marco T; ESCAPE Investigators. Effect of pulmonary hypertension on clinical outcomes in advanced heart failure: analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) database. Am Heart J. 2009;157(6):1026\u0026ndash;34. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ahj.2009.02.022\u003c/span\u003e\u003cspan address=\"10.1016/j.ahj.2009.02.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bratislava-medical-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Bratislava Medical Journal](https://link.springer.com/journal/44411)","snPcode":"44411","submissionUrl":"https://submission.springernature.com/new-submission/44411/3","title":"Bratislava Medical Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"HFrEF, pre- and post-capillary pulmonary hypertension, heart transplant","lastPublishedDoi":"10.21203/rs.3.rs-9382853/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9382853/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe recent definition of pulmonary hypertension (PH) has expanded the category of combined pre- and post-capillary (CPC) PH. Its impact on PH prevalence and prognosis in advanced heart failure with reduced ejection fraction (HFrEF) remains unknown.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 175 HFrEF patients evaluated for heart transplantation, all of whom underwent comprehensive invasive and non-invasive work-up. To assess the prognostic impact of the updated PH definition, survival was compared according to the presence of PH and its phenotype.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePH was present in 83% of patients, 76% of these met CPC PH criteria. Applying the 2015 definition, 77% of patients would have had PH, with 46% of them classified as CPC PH. Presence of PH correlated with markers of advanced HFrEF course, but only larger left atrial diameter (HR 1.158; 95% CI 1.020\u0026ndash;1.315; p\u0026thinsp;=\u0026thinsp;0.024) and lower TAPSE (HR 0.811; 95% CI 0.674\u0026ndash;0.976; p\u0026thinsp;=\u0026thinsp;0.027) remained independent predictors. CPC PH patients were older, with higher prevalence of renal insufficiency, diabetes and worse central hemodynamics. Higher age (HR 1.045; 95% CI, 1.000-1.091; p\u0026thinsp;=\u0026thinsp;0.048), systolic pulmonary artery pressure determined non-invasively (HR 1.064; 95% CI, 1.018\u0026ndash;1.111; p\u0026thinsp;=\u0026thinsp;0.006) and pulmonary artery wedge pressure (HR 1.131; 95% CI, 1.015\u0026ndash;1.261; p\u0026thinsp;=\u0026thinsp;0.026) were only predictors of CPC PH. Presence of both PH and CPC PH was associated with worse 2-year outcome, defined as implantation of mechanical circulatory support or all-cause mortality.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe new PH definition minimally affects PH prevalence in advanced HFrEF but substantially increases CPC PH group, which remains associated with adverse prognosis.\u003c/p\u003e","manuscriptTitle":"Pulmonary hypertension in advanced heart failure with reduced ejection fraction. What are the consequences of the new definition?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-21 14:59:40","doi":"10.21203/rs.3.rs-9382853/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-30T10:20:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-30T09:45:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"180353011507528126444433838134375128405","date":"2026-04-19T09:48:48+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-18T17:25:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"323736509382306496238976986556893475452","date":"2026-04-17T09:26:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"108843132963863345690341861191130073599","date":"2026-04-15T14:47:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"99723801089021998491410367228909576250","date":"2026-04-14T09:03:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-13T20:34:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-13T07:07:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-13T07:07:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Bratislava Medical Journal","date":"2026-04-10T19:54:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bratislava-medical-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Bratislava Medical Journal](https://link.springer.com/journal/44411)","snPcode":"44411","submissionUrl":"https://submission.springernature.com/new-submission/44411/3","title":"Bratislava Medical Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"530bd744-86da-4746-8d45-5aa0243b46e5","owner":[],"postedDate":"April 21st, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-04-30T10:20:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-30T09:45:09+00:00","index":111,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T10:25:12+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-21 14:59:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9382853","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9382853","identity":"rs-9382853","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}