Impaired left atrial reservoir strain causes exercise-induced pulmonary hypertension in patients with preserved left ventricular ejection fraction

Impaired left atrial reservoir strain causes exercise-induced pulmonary hypertension in patients with preserved left ventricular ejection fraction | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Echocardiography This is a preprint and has not been peer reviewed. Data may be preliminary. 11 February 2025 V1 Latest version Share on Impaired left atrial reservoir strain causes exercise-induced pulmonary hypertension in patients with preserved left ventricular ejection fraction Authors : Masaki Kinoshita 0000-0002-2607-7829 [email protected] , Tatsuro Tasaka , Kaori Fujimoto , Makoto Saito 0000-0001-5880-208X , Sumiko Sato , Kazuhisa Nishimura , Katsuji Inoue , Shuntaro Ikeda , Takumi Sumimoto , and Osamu Yamaguchi Authors Info & Affiliations https://doi.org/10.22541/au.173924477.78754350/v1 Published Echocardiography Version of record Peer review timeline 279 views 166 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Purpose: Exercise-induced pulmonary hypertension (EIPH), assessed using exercise stress echocardiography (ESE), is important in diagnosing early stage of heart failure (HF) with preserved ejection fraction (EF) and affects exercise tolerance and prognosis. Left atrial (LA) reservoir strain, which reflects the left ventricular filling pressure, is an important factor in the diagnosis of HF. This study aimed to investigate the association between the LA reservoir strain at rest and EIPH. Methods: This retrospective analysis included 188 participants with a left ventricular EF ≥ 50% who underwent ESE. EIPH was defined as a peak tricuspid regurgitation (TR) pressure gradient > 50 mmHg. HF events (HF hospitalization or diuretic use with brain natriuretic peptide ≥ 100 pg/mL) were evaluated in patients with ≥ 3 months follow-up. Results: Thirty-four (18.1%) patients were diagnosed with EIPH. LA reservoir strain at rest with an optimal cutoff value of 21% identified patients, with 73% sensitivity and 59% specificity. Among the resting echocardiographic parameters, LA reservoir strain was independently associated with EIPH (odds ratio; 0.93, P = 0.018). Furthermore, adding LA reservoir strain to the TR-velocity significantly improved EIPH discrimination. During a median follow-up period of 336 days, 29 patients (21.6 %) experienced HF events. Patients with LA reservoir strain ≤ 21% had a fourfold increased risk of HF events after adjusting for age and HFA-PEFF score. Conclusion: LA reservoir strain at rest was associated with EIPH and HF events in patients with preserved EF, suggesting that impaired LA reservoir strain could increase the risk of HF. Original article Title Impaired left atrial reservoir strain causes exercise-induced pulmonary hypertension in patients with preserved left ventricular ejection fraction Running title Impact of left atrial reservoir strain on exercise-induced pulmonary hypertension Masaki Kinoshita, MD, PhD a *; Tatsuro Tasaka, MD a ; Kaori Fujimoto, MD, PhD a ; Makoto Saito, MD, PhD a ; Sumiko Sato, MD a ; Kazuhisa Nishimura, MD, PhD b ; Katsuji Inoue, MD, PhD b ; Shuntaro Ikeda, MD, PhD b ; Takumi Sumimoto, MD, PhD a ; Osamu Yamaguchi, MD, PhD b a Department of Cardiology, Kitaishikai Hospital, Ozu City, Ehime, Japan b Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime, Japan *Corresponding author Masaki Kinoshita, MD, PhD, Department of Cardiology, Kitaishikai Hospital, Ozu City, Ehime 795-8505, Japan Tel: +81-893-25-0535 Fax: +81-893-25-0465 E-mail: [email protected] Data availability statement Raw data were generated at Kitaishikai Hospital. Derived data supporting the study findings are available from the corresponding author [Masaki Kinoshita] on request. Funding statement None Conflict of interest disclosure The authors declare no conflict of interest.All authors declare no relationships with industry relevant to this paper. Ethics of approval statement Institutional Review Board Approval of Kitaishikai Hospital was obtained (Approval no: 202401). Patient consent statement Informed consent was obtained from the patient as an opt-out form on the Kitaishikai Hospital website. Acknowledgments We are grateful to the sonographers (Norika Mise, Mai Hisano, Suguru Hisano, Daisuke Wake, Yoshiko Kawachi, Shizuko Nishio, and Rieko Higaki) for obtaining echocardiographic images and Editage (www.editage.jp) for English language editing. ABSTRACT Purpose: Exercise-induced pulmonary hypertension (EIPH), assessed using exercise stress echocardiography (ESE), is important in diagnosing early stage of heart failure (HF) with preserved ejection fraction (EF) and affects exercise tolerance and prognosis. Left atrial (LA) reservoir strain, which reflects the left ventricular filling pressure, is an important factor in the diagnosis of HF. This study aimed to investigate the association between the LA reservoir strain at rest and EIPH. Methods: This retrospective analysis included 188 participants with a left ventricular EF ≥ 50% who underwent ESE. EIPH was defined as a peak tricuspid regurgitation (TR) pressure gradient > 50 mmHg. HF events (HF hospitalization or diuretic use with brain natriuretic peptide ≥ 100 pg/mL) were evaluated in patients with ≥ 3 months follow-up. Results: Thirty-four (18.1%) patients were diagnosed with EIPH. LA reservoir strain at rest with an optimal cutoff value of 21% identified patients, with 73% sensitivity and 59% specificity. Among the resting echocardiographic parameters, LA reservoir strain was independently associated with EIPH (odds ratio; 0.93, P = 0.018). Furthermore, adding LA reservoir strain to the TR-velocity significantly improved EIPH discrimination. During a median follow-up period of 336 days, 29 patients (21.6 %) experienced HF events. Patients with LA reservoir strain ≤ 21% had a fourfold increased risk of HF events after adjusting for age and HFA-PEFF score. Conclusion: LA reservoir strain at rest was associated with EIPH and HF events in patients with preserved EF, suggesting that impaired LA reservoir strain could increase the risk of HF. Keywords: left atrial reservoir strain, exercise-induced pulmonary hypertension, heart failure, exercise stress echocardiography Non-standard Abbreviations and Acronyms ACE-I: angiotensin-converting enzyme inhibitorARB: angiotensin receptor blocker ARNI: angiotensin receptor-neprilysin inhibitor AUC: area under the curveBNP: brain natriuretic peptideBP: blood pressureBSA: body surface areaCI: confidence intervalE: early diastolic transmitral flow velocitye′: early diastolic mitral annular motionEF: ejection fractioneGFR: estimated glomerular filtration rateEIPH: exercise-induced pulmonary hypertensionESE: exercise stress echocardiographyGLS: global longitudinal strainHF: heart failureHFpEF: heart failure with preserved ejection fractionHR: hazard ratioIQR: interquartile rangeIVST: interventricular septal wall thickness LA: left atrialLAVI: left atrial volume indexLV: left ventricularLVEF: left ventricular ejection fractionLVGLS: left ventricular global longitudinal strain LVMI: left ventricular mass index MR: mitral regurgitation MRA: mineralocorticoid receptor antagonist OR: odds ratioPAP: pulmonary artery pressurePG: pressure gradientPH: pulmonary hypertensionPVR: pulmonary vascular resistance PWT: posterior wall thickness ROC: receiver operating characteristicSGLT2: sodium-glucose cotransporter 2 TR: tricuspid regurgitationVHD: valvular heart disease INTRODUCTION Exercise-induced pulmonary hypertension (EIPH) is a condition in which pulmonary arterial pressure increases during physical activity and frequently observed in patients with heart failure (HF), regardless of left ventricular ejection fraction (LVEF) 1 . Although this condition can lead to symptoms, such as exercise intolerance and exertional dyspnea, it is considered an early or mild stage of pulmonary hypertension (PH) 2,3 . EIPH leads to poor clinical outcomes in patients with reduced LVEF and valvular heart disease (VHD) 4–6 . Additionally, EIPH is documented in approximately one-third of patients with preserved LVEF and increases the risk of cardiovascular events and deaths 7,8 . In clinical practice, EIPH is often evaluated by exercise-stress echocardiography (ESE). However, the number of facilities in which ESE can be performed is limited, and some patients find it difficult to perform because of motion restrictions caused by reduced activities of daily living or orthopedic diseases 9 . Therefore, it would be beneficial to predict EIPH using resting echocardiographic findings. Presently, it has been reported that factors related to increased left ventricular (LV) filling pressure or left atrial (LA) pressure, such as older age, LA enlargement, higher the ratio of early diastolic transmitral flow velocity (E) and early diastolic mitral annular motion (e′), significant VHD, and elevated tricuspid regurgitation (TR)-velocity, was associated with EIPH 1,7,8 . LA reservoir strain, which is a critical indicator of LA performance and marker of LV filling pressure, provides valuable information about cardiac function and disease progression and could be an important therapeutic target in HF with preserved ejection fraction (HFpEF) 10–12 . Hence, we hypothesized that LA reservoir strain causes EIPH in patients with preserved LVEF. This study aimed to clarify the association between LA reservoir strain and EIPH. Therefore, we investigated the effect of LA reservoir strain on EIPH and HF events in patients with preserved LVEF. MATERIALS AND METHODS Study design and population This retrospective, observational, single-center cohort study conducted at Kitaishikai Hospital (Ozu, Japan) was designed according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement 13 . All procedures were performed in accordance with the Declaration of Helsinki (2013 amendment) and Good Clinical Practice guidelines. The study protocol was approved by the Institutional Review Board of Kitaishikai Hospital (Approval No. 202401). Since this is a retrospective study, informed consent was obtained through an opt-out form on the Kitaishikai Hospital website. We included 222 consecutive patients who had LVEF ≥ 50% at rest and underwent ESE without duplicates from an echocardiographic database between July 2021 and December 2024. Patients with PH, defined as a TR pressure gradient (PG) > 50 mmHg at rest, dialysis, severe left-sided VHD, chronic respiratory diseases, including chronic obstructive pulmonary disease and interstitial lung disease, and previous mitral valve surgery were excluded based on medical records. Additionally, patients with poor-quality images that could not be used to measure TR velocity and LA strain were excluded. We gathered data from the medical records of several clinical parameters to investigate the factors associated with EIPH. These data included age, sex, body surface area, vital signs (heart rate and blood pressure), comorbidities, medical history, medications, laboratory data, and echocardiographic findings. HF stage C was classified as symptomatic HF, and the HFA-PEFF score at rest in Step2 as recommended by the Heart Failure Association of the European Society of Cardiology was calculated 14,15 . Outcome The primary outcome of this study was EIPH, defined as a peak TRPG > 50 mmHg at maximum exercise 16 . Patients were followed-up from the date of ESE until December 31, 2024. The secondary outcome was HF events based on the medical records of patients with ≥ 3 months of follow-up. HF events were defined as HF hospitalization or the administration of diuretics with brain natriuretic peptide (BNP) ≥ 100 pg/mL. All patients were censored upon secondary outcome or at the end of the follow-up period. Rest and exercise stress echocardiography Several expert sonographers with > 8 years of experience performed two-dimensional transthoracic echocardiography using a commercially available ultrasound system (Vivid E95; GE Healthcare). Echocardiographic images at rest and during exercise were recorded for three cardiac cycles in sinus rhythm and five cardiac cycles in atrial fibrillation. All echocardiographic data were analyzed using EchoPAC software (EchoPAC ver. 204.91.0; GE Healthcare). Additionally, ESE was performed using an ergometer in the semi‐supine and left lateral decubitus positions (Ergoselect 12; Inter‐Reha Co. Ltd.). The workload started at 25 W and increased by 25 W every 3 min until the participant reported exhaustion 17 . Echocardiographic parameters were obtained according to the American Society of Echocardiography 18,19 . The LVEF and LA volume were evaluated using the biplane disk summation method. The LA volume was indexed to the body surface area. E in the apical long-axis view was obtained using pulsed-wave Doppler, and the sample volume was placed at the level of the mitral valve tip. Subsequently, e′ was assessed at the septal and lateral mitral annular sites in the apical four-chamber view and the E/e′ ratio was calculated. LV global longitudinal strain (GLS) and LA reservoir strain were measured with high frame rates (> 60 frames/s) using speckle-tracking echocardiography. The LA reservoir strain analyzed with a zero-strain reference set at LV end-diastole was assessed for an apical four-chamber view based on a consensus document of the EACVI/ASE/Industry Task Force 20 . Statistical analysis Continuous variables were tested for normal distribution and reported as median (interquartile range [IQR]). Categorical variables are presented as numbers and percentages. Patients categorized into two groups (EIPH or non-EIPH) were compared using Student’s t -test, Mann–Whitney U , Wilcoxon rank-sum test, and Chi-squared test. Receiver operating characteristic (ROC) curve area under the curve (AUC) was used to predict the primary outcome. The optimal cutoff value was determined if the sum of the sensitivity and 1 - specificity reached its maximum. Enhancements in predictive accuracy and model performance were evaluated using the likelihood ratio test and C-statistics. Associations between the primary outcomes and LA reservoir strain were determined using univariate and multivariate logistic regression analyses. Previously, age, atrial fibrillation, HFA-PEFF score, LA function, E/e′ ratio, and TR-velocity as risk factors for EIPH and HFpEF were used as covariates in the multivariate analysis. Secondary outcomes were assessed using Kaplan–Meier analysis and compared using the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were conducted to evaluate the association with outcome risk and compute the hazard ratio (HR) along with a 95% confidence interval (CI) for the secondary outcome. All data were statistically analyzed using ’EZR’ (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria), and GraphPad Prism version 10.4.1.627 (Boston, Massachusetts, USA) 21 . Statistical significance was set at P < 0.05. Baseline characteristics All patients experienced no adverse events during ESE. A flowchart of the selection of the study participants is shown in Figure 1. We analyzed data from 188 patients (median age; 72 years [IQR; 63‒80 years]; median LVEF at rest, 62% [IQR: 58‒67%]; 28% women) after excluding those with PH at rest (n = 3), dialysis (n = 4), severe left-sided VHD (n = 7), chronic respiratory diseases (n = 13), previous mitral valve surgery (n = 1), and poor echocardiographic image quality (n = 6 [no TR-velocity = 2, no LA strain = 4]) (Figure 1). Of the 188 patients, 34 (18.1%) were diagnosed with EIPH. The participants’ characteristics are presented in Table 1. Age and BNP levels were higher in the EIPH group than in the non-EIPH group. The proportions of HF stage C, hypertension, and chronic kidney disease were higher in the EIPH group than in the non-EIPH group. Oral medications showed no significant differences, excluding sodium-glucose cotransporter 2 (SGLT2) inhibitors. Echocardiographic parameters Resting echocardiographic findings are shown in Table 2. No significant intergroup differences were observed in LV systolic function, including LVGLS. LA volume index (LAVI), E/e′ ratio, and TR-velocity were higher in the EIPH group than in the non-EIPH group. Furthermore, the LA reservoir strain was significantly lower in the EIPH group than in the non-EIPH group. Association between LA reservoir strain and EIPH The cut-off value of LA reservoir strain determined by the ROC curve was 21%, with 73.5% sensitivity and 59.1% specificity for identifying patients with EIPH (AUC; 0.69, 95% CI; 0.59–0.79, P < 0.001, Figure 2). Additionally, the AUC values of LAVI, E/e′ ratio, and TR-velocity to distinguish between the EIPH and non-EIPH groups were 0.65 (95% CI; 0.55–0.76, P = 0.005 ), 0.64 (95% CI; 0.54–0.74, P = 0.011) , and 0.76 (95% CI; 0.68–0.84, P < 0.001) , respectively (Figure 2). The AUC of the E/e ratio was the only one that showed a significantly lower value than that of the TR-velocity ( P = 0.035). Univariate logistic regression analysis revealed that the LA reservoir strain, LAVI, E/e ratio, TR-velocity, and age were significantly associated with EIPH (Table 3). Furthermore, multivariate logistic regression analysis revealed that LA reservoir strain was independently associated with EIPH (Table 3). Adding LAVI and E/e′ ratio to TR-velocity did not result in a significant improvement, but adding LA reservoir strain improved the discrimination between patients with and without EIPH (C-statistics 0.80, P = 0.006) (Figure 3). Impact of LA reservoir strain on HF events Of the 188 patients, 134 (71.3%) were followed-up for ≥ 3 months. During a median observation period of 336 days (IQR; 176–‒537 days), 29 (21.6%) patients experienced HF events, including nine HF hospitalizations. In the Kaplan–Meier curves, LA reservoir strain ≤ 21% (the cut-off value determined by the ROC curve for identifying EIPH) had significantly more HF events (log-rank test, P < 0.001) (Figure 4). In the univariate Cox proportional hazard regression analysis, patients with LA reservoir strain ≤ 21% were associated with a nine-fold increased risk of HF event compared with LA reservoir strain > 21% (HR; 9.15, 95% CI; 3.18‒26.3, P < 0.001) (Table 4). Furthermore, in the multivariate Cox hazard model, the patient with LA reservoir strain ≤ 21% was independently associated with a six-fold increased risk of HF events after adjustment for atrial fibrillation (HR; 6.18, 95% CI; 1.99–19.2, P = 0.002) and four-fold risk after adjusting for age and the HFA-PEFF score at rest (HR; 4.04, 95% CI; 1.29–12.7, P = 0.017) (Table 4). DISCUSSION This retrospective single-center cohort study investigated the effect of LA reservoir strain at rest on EIPH and HF events in patients with preserved LVEF. The study findings indicate that the LA reservoir strain at rest is independently associated with EIPH and has an incremental benefit in distinguishing patients with EIPH. Furthermore, impaired LA reservoir strain is associated with an increased risk of HF events in patients with preserved LVEF. The incidence of EIPH is reportedly approximately 12–34% in patients with preserved LVEF 8,22 . In this study, the proportion of elderly patients was high; therefore, the development of EIPH may be higher (18.1%). This may have been influenced by the exclusion of high-risk cases, such as those with severe left-sided VHD and chronic respiratory diseases. The relatively low prevalence of HFpEF (HF stage C; 38.3%) may be another reason. The extent of PH is not independently correlated with the severity of LV systolic dysfunction, but is associated with abnormalities in LV diastolic filling 23 . A marked increase in pulmonary artery pressure (PAP) is observed during exercise because of exercise-induced elevations in LV filling pressure and LA pressure, whereas cardiac output increases. PAP is usually affected by the LA pressure and pulmonary vascular resistance (PVR) 24 . In healthy individuals and patients with HFpEF, the PVR decreases during exercise owing to pulmonary vascular recruitment and distension 25,26 . Therefore, the increase in PAP was primarily attributed to an increase in the LA pressure 27 . Previously, EIPH was strongly associated with older age, higher E/e′ ratio, dilated left atrium, and TR-velocity at rest 7,8,22 . Similarly, we found that age, E/e′ ratio, TR velocity, and LA function (LAVI and LA reservoir strain) at rest were associated with EIPH. These findings are characteristic of HFpEF and suggest that EIPH is an important factor in the early diagnosis of HFpEF. Moreover, the study results indicated that a significantly higher proportion of HF stage C (58.8% vs. 33.8%) was present in the EIPH group. Furthermore, EIPH caused by elevated LV filling pressure or LA pressure results in poor prognostic outcomes 7 . LV diastolic dysfunction is a key pathophysiological mechanism of HFpEF 10,15,18 . In the early phase of LV diastolic dysfunction, the left atrium works harder to compensate for the impaired LV filling resulting from decreased left ventricular compliance. Consequent to chronic LV diastolic dysfunction and elevated LV filling pressure, the diastolic function and compliance of the left atrium progressively decline. This leads to reduced LA reserve, eventually causing LA enlargement and dysfunction 28 . Particularly, the reservoir function in the left atrium is affected by abnormalities in LV filling and compliance 29 . LA reservoir strain is an excellent parameter for evaluating LA reservoir function under various conditions and has been suggested as an alternative method for assessing LV filling pressure 30 . Hence, the LA reservoir strain is closely linked to adverse cardiovascular outcomes in patients with HF. Freed et al. reported that LA reservoir strain was an independent predictor of hospitalization and death in patients with HFpEF 31 . Moreover, assessing the LA reservoir strain can reliably identify patients with HFpEF, and impaired it is independently associated with abnormal exercise hemodynamics 11 . This is consistent with our findings that LA reservoir strain is independently associated with EIPH caused by elevated LV filling pressure and HF events. Limitations This retrospective study was conducted at a single center and had several limitations. First, this study was a single-center retrospective analysis. Therefore, these results should be regarded as preliminary and require further validation through additional studies. Second, six of the 194 patients (3.1%) could not be assessed for LA strain or TR-velocity because of poor echocardiographic image quality. Third, the influence of potential confounders may have been included in the multivariate Cox regression analysis because of the small number of outcomes (29 events). Finally, the cutoff value of LA reservoir strain was calculated using ROC curve analysis for the association with outcome risk in a limited population, and external validation is needed to generalize the study results. Conclusion LA reservoir strain at rest was independently associated with the occurrence of EIPH in patients with preserved LVEF. Assessing LA reservoir strain had an incremental benefit in identifying the EIPH and non-EIPH groups. Additionally, reduced LA reservoir strain was independently associated with a higher risk of HF events. Our findings suggest that the risk stratification of patients with preserved LVEF may be possible by recognizing impaired LA reservoir strains. However, additional studies with internal and external validation are required to confirm the applicability of these findings. References 1. Ha JW, Choi D, Park S, et al. Determinants of exercise-induced pulmonary hypertension in patients with normal left ventricular ejection fraction. Heart . 2009;95(6):490-494.2. Proudman SM, Stevens WM, Sahhar J, et al. Pulmonary arterial hypertension in systemic sclerosis: The need for early detection and treatment. Intern Med J . 2007;37(7):485-494. 3. 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Left atrial strain: a new parameter for assessment of left ventricular filling pressure. Heart Fail Rev . 2016;21(1):65-76.31. Freed BH, Daruwalla V, Cheng JY, et al. Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure with Preserved Ejection Fraction: Importance of Left Atrial Strain. Circ Cardiovasc Imaging . 2016;9(3):1-10. Figure legends Figure 1. Flowchart in the selection of patients. EIPH, exercise-induced pulmonary hypertension; ESE, exercise stress echocardiography; PH, pulmonary hypertension; VHD, valvular heart disease. Figure 2. Receiver operating characteristic curves for identification of exercise-induced pulmonary hypertension by resting echocardiographic parameters. The AUC values of LA reservoir strain, LAVI, E/e′, and TR velocity for distinguishing between the EIPH and non-EIPH groups were 0.69, 0.65, 0.64, and 0.76, respectively. There are no significant differences between the AUC values of the TR velocity and LA factors, excluding E/e′ . AUC, area under the curve; E/e′, early diastolic transmitral flow velocity and early diastolic mitral annular motion; EIPH, exercise-induced pulmonary hypertension LA, left atrial; LAVI, left atrial volume index; TR, tricuspid regurgitation Figure 3. Incremental value of left atrial reservoir strain over models based on resting echocardiographic parameters associated with exercise-induced pulmonary hypertension. E/e′, early diastolic transmitral flow velocity and early diastolic mitral annular motion; LA, left atrial; LAVI, left atrial volume index; TR, tricuspid regurgitation. Figure 4. Kaplan–Meier curves for the free of heart failure events according to left atrial reservoir strain. LA reservoir strain ≤ 21% was associated with significantly more HF events compared to LA reservoir strain > 21%. HF, heart failure; LA, left atrial Supplementary Material File (table 1.docx) Download 22.77 KB File (table 2.docx) Download 20.49 KB File (table 3.docx) Download 19.48 KB File (table 4.docx) Download 18.04 KB Information & Authors Information Version history V1 Version 1 11 February 2025 Peer review timeline Published Echocardiography Version of Record 20 Mar 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Collection Echocardiography Keywords exercise stress echocardiography exercise-induced pulmonary hypertension heart failure left atrial reservoir strain Authors Affiliations Masaki Kinoshita 0000-0002-2607-7829 [email protected] Kitaishikai Hospital View all articles by this author Tatsuro Tasaka Kitaishikai Hospital View all articles by this author Kaori Fujimoto Kitaishikai Hospital View all articles by this author Makoto Saito 0000-0001-5880-208X Kitaishikai Hospital View all articles by this author Sumiko Sato Kitaishikai Hospital View all articles by this author Kazuhisa Nishimura Ehime Daigaku Daigakuin Igakukei Kenkyuka Igakubu View all articles by this author Katsuji Inoue Ehime Daigaku Daigakuin Igakukei Kenkyuka Igakubu View all articles by this author Shuntaro Ikeda Ehime Daigaku Daigakuin Igakukei Kenkyuka Igakubu View all articles by this author Takumi Sumimoto Kitaishikai Hospital View all articles by this author Osamu Yamaguchi Ehime Daigaku Daigakuin Igakukei Kenkyuka Igakubu View all articles by this author Metrics & Citations Metrics Article Usage 279 views 166 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Masaki Kinoshita, Tatsuro Tasaka, Kaori Fujimoto, et al. Impaired left atrial reservoir strain causes exercise-induced pulmonary hypertension in patients with preserved left ventricular ejection fraction. Authorea . 11 February 2025. DOI: https://doi.org/10.22541/au.173924477.78754350/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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