Severe Heart Failure and Outcomes in 121 Children With Dilated Cardiomyopathy: A Single-Center Retrospective Study from Southwest China

Severe Heart Failure and Outcomes in 121 Children With Dilated Cardiomyopathy: A Single-Center Retrospective Study from Southwest China | 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 Severe Heart Failure and Outcomes in 121 Children With Dilated Cardiomyopathy: A Single-Center Retrospective Study from Southwest China Cheng Chen, Danyan Su, Suyuan Qin, Bingbing Ye, Yanyun Huang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1352003/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective Heart failure is a common complication in children with dilated cardiomyopathy. The aim of this study was to determine whether severe heart failure at diagnosis was related to poor outcomes in children with dilated cardiomyopathy. Methods We analyzed medical data from 121 children with dilated cardiomyopathy in our hospital from 2003 to 2021. The children were grouped by the degree of heart failure. Cox regression analysis was performed to confirm whether severe heart failure was associated with poor outcomes. Results There were 121 patients with dilated cardiomyopathy in this research. The mean age of the 121 patients was 118.5 ± 63.0 months. Of these patients, 81 (67.8%) were sorted into a severe heart failure group and 39 (32.2%) were placed into a mild heart failure group. A comparison between the two groups showed that patients with severe heart failure were older and more likely to be male, have lower systolic blood pressure measurements, be admitted to the intensive care unit and be treated with β-blockers, loop diuretics, spironolactone and digoxin. In addition, they had larger systolic and diastolic left ventricular end-diastolic dimensional and lower left ventricular ejection fractional z-scores as well as being more prone to aortic and tricuspid regurgitations (P < 0.05 in all cases). After adjusting for age, sex, heart rate, left ventricular ejection fraction z-scores and drug, severe heart failure was found to be independently associated with an increased risk of death (hazard ratio [HR] 2.27; P < 0.005). Conclusions Severe heart failure at diagnosis was related to a greater risk of death in children with dilated cardiomyopathy. Further prospective studies are warranted to evaluate the efficacy between the treatment undertaken for heart failure and outcomes in children with dilated cardiomyopathy. Dilated cardiomyopathy heart failure children management prognosis Figures Figure 1 Introduction Dilated cardiomyopathy (DCM) is a progressive and serious disorder of the heart muscle which is characterized by the dilation of the left ventricle accompanied by a reduction of systolic function[ 1 ]. DCM is diagnosed in 0.57 cases per 100 000 children /year in the United States and has a 20% mortality rate at 1 year and a 56% mortality rate at 4 years[ 2 , 3 ]. Although the prognosis of children with DCM have increased in the past 20 years[ 4 ], the management of patients with this condition needed to be more targeted and precise in order to raise long-term prognosis. Heart failure (HF) is a severe complication of DCM and a major cause of heart transplantation or sudden death in children with DCM [ 2 , 5 ]. Improvement of HF can reverse cardiac histologic remodeling and increase the prognosis of DCM[ 6 , 7 ]. With the release of the European Society of Cardiology and American College of Cardiology Guidelines for HF in 2021, the management of HF has become more standardized and effective[ 8 , 9 ]. Therefore, we performed a novel analysis comparing children with severe HF who were classified as ROSS/NYHA class III or class IV to those with mild HF who were classified as ROSS/NYHA class I or class II. We hypothesized that severe HF is related to poor prognosis in children with DCM. Methods Study Subjects Children aged ≤ 18 years with a diagnosis of DCM admitted to the First Affiliated Hospital of Guangxi Medical University between March 2003 and September 2021 were enrolled into the study. The exclusion criteria included ① congenital heart disease, arrhythmia cardiomyopathy, ischemic heart disease, cardiac valve disease and hypertensive heart disease; ② DCM with known etiology, such as drug-induced cardiomyopathy and inherited metabolic cardiomyopathy such as primary carnitine deficiency. Definitions Diagnosis of DCM was indicated by a left ventricular end-diastolic dimension (LVEDD) of more than two standard deviations (SDs) above normal for the individual’s body surface area (or z -score for age > 2) and a left ventricular ejection fraction (LVEF) or left ventricular fractional shortening (LVFS) of lower than 2 standard deviations for healthy children of the same age (or z -score for age < 2). Severe HF was defined as an improved ROSS scoring criteria (≥ 7score)[ 10 ] or NYHA class III/IV and mild HF was defined as an improved ROSS scoring criteria (༜7score) or NYHA class I/II. Study Methods General data involved age, race, sex and body mass index (BMI), HF at diagnosis, duration of symptoms, duration of stay in hospital, multiple hospitalizations (≥ 2 visits), admission to the intensive care unit, family history of DCM, heart rate at diagnosis, systolic and diastolic blood pressure measurements at diagnosis, echocardiographic measurements z-scores, medications, follow-up periods and outcomes. The patients were classified into either a severe and or a mild HF group based on the severity of HF. The primary adverse event was death. Statistical Analysis Data analyses were performed employing SPSS software (version 24.0 for Windows, SPSS, Inc., Chicago, Illinois). Data are presented either as means or percentages. Continuous variates were compared using Student’s t test (for normally distributed data) or Wilcoxon rank sum test (for non-normally distributed data), and categorical variates were compared with chi-square tests. Kaplan–Meier plots were established, and log-rank statistics were employed to evaluate survival differences at specific time points of 12, 24 and 60 months after enrollment as well as overall survival. Cox regression was performed to confirm the factors independently related to worse outcomes to reduce selection bias among children involved in the study. Hazard ratios (HR) and 95% confidence intervals (95% CI) were used to present the data. P < 0.05 was identified statistically significant. Results Clinical Characteristics There were 121 DCM patients in this cohort. The mean age of the 121 patients was 118.5 ± 63.0 months. Of these, 81 (67.8%) patients were grouped as severe HF and 39 (32.2%) were placed in a mild HF group. Table 1 presents the demographic information, clinical indicators, echocardiographic characteristics, medications used at the time of cardiomyopathy diagnosis, time period of follow-up and the outcomes of patients who were classified as severe HF compared with those who were classified as mild HF. There were no significant differences between the groups when compared by race, duration of symptoms, duration in the first hospitalization, multiplicity of hospitalizations, family history of DCM, BMI, heart rate and systolic blood pressure. Nevertheless, patients with severe HF were older, more likely to be male, have lower systolic pressure, be admitted to the intensive care unit and be treated with β-blockers, loop diuretics, spironolactone and digoxin. Patient with severe HF were more likely to have lower LVEF z-scores, larger systolic and diastolic LV dimensional z-scores, and more likely to suffer from aortic and tricuspid regurgitations. Table 1 Demographics, clinical indicators, echocardiographic measurement, drug use, time of follow-up and Outcomes of the patients in this study. Parameter Overall (n = 121) Severe HF (n = 82) Mild HF (n = 39) p Age, (mean ± SD), m 118.5 ± 63.0 129.5 ± 64.5 95.4 ± 53.5 0.005 Male, n (%) 69 (57.0%) 52 (63.4%) 17 (43.5%) 0.04 Race, n (%) 0.865 Han 58 (47.9%) 38 (46.3%) 20 (51.3%) Zhuang 57 (47.1%) 40 (48.8%) 17 (43.6%) Others 6 (5.0%) 4 (4.9%) 2 (5.1%) Duration of symptoms, (mean ± SD), m 4.0 ± 9.6 3.9 ± 8.9 4.2 ± 11.1 0.899 Duration in first hospitalization, (mean ± SD), d 11.8 ± 10.4 12.5 ± 11.3 10.5 ± 8.0 0.342 Multiple hospitalizations, n (%) 51 (42.1%) 39 (47.6%) 12 (30.8%) 0.08 Admission to intensive care unit, n (%) 53 (43.8%) 45 (54.8%) 8 (20.5%) < 0.001 Family history of dilated cardiomyopathy, n (%) 10 (8.3%) 8 (9.7%) 2 (5.1%) 0.388 Body mass index, (mean ± SD) 16.3 ± 3.3 16.7 ± 3.5 15.6 ± 2.6 0.089 Heart rate at admission, (mean ± SD) 113.4 ± 21.9 114.2 ± 20.8 111.7 ± 24.3 0.574 systolic blood pressure at admission, (mean ± SD) 99.3 ± 14.4 97.2 ± 14.4 104.1 ± 13.4 0.017 diastolic blood pressure at admission, (mean ± SD) 64.8 ± 11.5 64.2 ± 11.5 66.1 ± 11.6 0.417 Medications at diagnosis N (%) ACEI/ARNI 103 (85.1%) 71 (86.5%) 32 (82.0%) 0.512 β-blocker 37 (30.5%) 30 (36.5%) 7 (17.9%) 0.038 Loop diuretic 114 (94.2%) 81 (98.7%) 33 (84.6%) 0.002 Spironolactone 111 (91.7%) 78 (95.1%) 33 (84.6%) 0.05 Digoxin 114 (94.2%) 81 (98.7%) 33 (84.6%) 0.002 Intravenous inotropes 61 (50.4%) 46 (56.1%) 15 (38.4%) 0.07 LV echocardiographic z scores, (mean ± SD) LVEDD z scores 7.3 ± 2.8 7.7 ± 2.6 6.5 ± 2.8 0.033 LVESD z scores 10.4 ± 3.3 10.8 ± 3.1 9.4 ± 3.5 0.035 LVEDPWT z scores 0.9 ± 2.4 0.9 ± 2.7 0.9 ± 1.8 0.99 LVEDST z scores 0.2 ± 1.6 0.2 ± 1.7 0.2 ± 1.4 0.679 LV fractional shortening z scores -8.9 ± 4.8 -9.1 ± 5.3 -8.4 ± 3.7 0.411 LV ejection fraction z scores -6.5 ± 2.1 -7.0 ± 2.0 -5.6 ± 2.0 0.001 Mitral regurgitation, n (%) 80 (96.6%) 80 (97.5%) 37 (94.8%) 0.439 Aortic regurgitation, n (%) 10 (12.1%) 10 (12.1%) 0 (0.0%) 0.023 Tricuspid regurgitation, n (%) 104 85.9%) 74 (90.2%) 30 (76.9%) 0.049 Pulmonary regurgitation, n (%) 43 (35.5%) 32 (39.0%) 11 (28.2%) 0.245 Follow-up times 30.5 ± 42.9 24.4 ± 40.4 43.2 ± 45.7 0.024 Events 83 (68.5%) 65 (79.2%) 18 (46.1%) < 0.001 HF, heart failure; LVEDD, left ventricular end-diastolic dimension; LVESD, left ventricular end-systolic dimension; LVEDPWT, left ventricular end-diastolic posterior wall thickness; LVEDST, left ventricular end-diastolic septal thickness; ACEI, angiotensin-converting enzyme inhibitors; ARNI, angiotensin II receptor blocker neprilysin inhibitor. Outcomes The median follow-up time was 24.4 months for patients with severe HF and 43.2 months for patients with mild HF (P < 0.024). Of the 82 children with severe HF, 50 (60.9% at 12months), 56 (68.3% at 24 months), 65 (79.2% at 60 months) and 65 (79.2%, overall) died, whereas among the 39 children with mild HF, 9 (23.1% at 12 months), 12 (30.8% at 24 months), 18 (46.1% at 60 months) and 18 (46.1% overall) died (P < 0.001). Compared with those with mild HF, the time to death was shorter for children with severe HF (Fig. 1 , P < 0.001). Cox regression analysis was employed to confirm the factors related to the overall probability of death (Table 2 ). Severe HF increased the risk of death in unmodulated and in all modulated Cox regression analyses. This relationship was not weakened after modulating for various factors. However, after modulating for use of loop diuretics, severe HF was independently related to a higher risk of death (hazard ratio [HR] 2.27; 95% Cl, 1.28–4.03 in model 6). In model 6, use of loop diuretics was related to a decreased risk of death (Table 2 , hazard ratio [HR] 0.074; 95% Cl, 0.006–0.876, p<0.039). Table 2 Multivariate Cox regression modeling of severe heart failure versus mild heart failure. Outcome Variates Model 1 (n = 121) Model 2 (n = 121) Model 3 (n = 121) Model 4 (n = 121) Model 5 (n = 121) Model 6 (n = 121) Death Heart Failure (severe vs mild) 2.516 (1.488–4.255)<0.001 2.614 (1.538–4.440)<0.001 2.741 (1.603–4.686)<0.001 2.625 (1.524–4.620)<0.001 2.512 (1.448–4.357)<0.001 2.274 (1.280–4.038)<0.005 Age (months) 0.998 (0.995–1.002) 0.329 0.998 (0.995–1.002) 0.460 0.999 (0.996–1.003) 0.743 0.999 (0.995–1.003) 0.558 1.000 (0.995–1.004) 0.947 Sex 1.330 (0.854–2.073) 0.207 1.318 (0.847–2.051) 0.221 1.283 (0.821–2.006) 0.273 0.766 (0.475–1.237) 0.276 Heart Rate 1.005 (0.995–1.016) 0.335 1.004 (0.993–1.015) 0.445 1.005 (0.993–1.016) 0.418 LVEF z scores 0.949 (0.857–1.052) 0.320 0.935 (0.838–1.043) 0.225 ACEI/ARNI (yes vs no ) 1.214 (0.569–2.588) 0.615 β-blockers (yes vs no ) 1.035 (0.551–1.942) 0.915 Loop diuretics (yes vs no ) 0.074 (0.006–0.876) 0.039 Spirolactone (yes vs no ) 2.338 (0.756–7.232) 0.140 Digoxin (yes vs no ) 2.421 (0.406–16.912) 0.311 Intravenous inotropes (yes vs no ) 0.943 (0.577–1.542) 0.815 Hazard ratios (95% CIs) and P values were used to show data. Variates were employed according to the statistics in Table 1 (P < 0.05) or prognostic indicator. Model 1 is a one-variable Cox regression analysis with heart failure (HF) variable (severe HF vs mild HF). Model 2 modulates for age. Model 3 ulteriorly modulates for sex (male/female) besides the variates in Model 2. Model 4 ulteriorly modulates for heart rate besides the variates in Model 3. Model 5 ulteriorly modulates for LV ejection fraction z score besides the covariates employed in Model 4. Model 6 ulteriorly modulates for drug (including either ACEI or ARNI, and beta blockers, loop diuretics, spironolactone, digoxin and intravenous inotropes) besides the variates employed in Model 5. Discussion The study demonstrates that children with DCM and severe HF at diagnosis were older, more likely to be male, have lower systolic blood pressure measurements, be admitted to the ICU and be treated with β-blockers, loop diuretics, spironolactone and digoxin. They are also more likely to have larger diastolic LV end-diastolic dimensional z-scores and poorer LV function. Compared with children with DCM and mild HF, those with DCM and severe HF at diagnosis were at a higher risk of death. Severe HF was related to an accumulated risk of death. These associations were not affected by sex, age at diagnosis, heart rate, ventricular function and use of medication. These results are similar to those found in a study by Rusconi [ 11 ]. They showed similar results with respect to survival between family-associated DCM and idiopathic DCM after modulation for other variates. However, HF, older age, and larger left ventricular end-diastolic dimension (LVEDD) at diagnosis were independently related to increased risks of the major adverse events of heart transplantation or death. In a retrospective analysis, HF with NYHA III/IV were significantly associated with overall death risk[ 12 ]. A meta-analysis of 57 researches of medication adherence interventions for HF treatment from adults found an obvious association between improvement of HF and a decrease of mortality[ 13 ]. These findings lend support to the idea that an improvement in HF may be a key goal for DCM therapy. Angiotensin-converting enzyme inhibitors (ACEI) is the cornerstone of HF treatment and can significantly improve cardiac remodeling. The beneficial effects of ACEI for HF in children with DCM have been proven in previous studies[ 14 , 15 ]. One prospective and large-sample study which included 5,955 adult patients with DCM and LVEF < 40% also confirmed that use of ACEI was related to the recovery of the LVEF coupled with an improvement of HF at 3 years of follow-up[ 16 ]. In a European survey between pediatric HF and ACEI use patterns conducted between January and May 2015, ACEI appeared to be essential in pediatric HF treatment strategies[ 17 ]. Nowadays, the angiotensin II receptor blocker, neprilysin inhibitor (ARNI), is more effective when compared with ACEI, and this drug has now been recommended to be the preferred treatment in patients with HF[ 8 , 9 , 18 ]. In children with DCM and HF, elevated heart rate is often accompanied by worsening HF. Thus, the heart rate may be a target for HF treatment. Beta blockers can reduce heart rate. Three meta-analysis on the use of beta-blockers for congestive HF in children showed that children with congestive HF might benefit from treatment with these drugs[ 19 – 21 ]. Additionally, ivabradine is a novel drug which can reduce the heart rate. A study randomized 116 patients diagnosed with DCM and class II to IV HF. In this study, the heart rate was reduced by ≥ 20% from baseline without leading to symptoms or bradycardia were more likely to occur in the patients taking ivabradine rather than taking the placebo. This reduction was accompanied with a significant increase in the LVEF, an improvement of the cardiac function as well as in the quality of life[ 22 ]. Another adult study also showed that the reduction of heart rate in the ivabradine group could improve the prognosis of HF[ 23 ]. In our study, loop diuretics was related to a decreased risk of death. Diuretics are also another important treatment for HF. A meta-analysis of 14 studies with 525 participants of the use of diuretic in HF suggested that these were able to reduce mortality and retard progression of HF [ 24 ]. In a study of 25,345 elder patients with HF, patients with loop diuretics as a discharge prescription had a better clinical improvement comparing with those not taking loop diuretics[ 25 ]. One study included 108 children and showed that an increase of loop diuretic responsiveness during the first 72 hours of treatment was accompanied by shorter length of hospital stays and a decrease of inpatient deaths or use of mechanical circulatory support[ 26 ]. In addition to loop diuretics, a mineralocorticoid receptor antagonist (MRA), such as spironolactone, which can also have a diuretic effect, is fundamental during the long-term management of HF[ 27 ]. There are several emerging treatments for HF in children with DCM. In a meta-analysis study, sodium-glucose co-transporter-2 (SGLT2) inhibitors were shown to reduce all-cause and cardiovascular death in patients with HF [ 28 ], and these drugs are recommended to be the preferred choice of treatment in patients with HF[ 8 , 9 ]. Pulmonary artery banding (PAB) treatment, as a new indication for end-stage DCM in pediatric patients, has also been shown to be safe and effective[ 29 , 30 ]. Left ventricular mechanical assist can be indicated as destination therapy for end-stage DCM[ 31 ]. Cardiac pacemaker can be an effective tool for treating HF, especially in patients who have a complete left bundle branch block[ 32 ]. Cardiac stem cell therapy is yet another feasible and safe treatment in children with DCM and HF, and can improve left ventricular function[ 33 ]. If none of the above methods work, heart transplantation could be considered as a last resort[ 34 ]. As we have already confirmed that severe HF is related to a higher risk of death in children with DCM, so therapies that improve HF can increase survival. Through a more comprehensive understanding of DCM, especially with respect to the genetics of DCM and the potential of finding new early markers and treatment for HF, it is envisaged that the treatment of HF caused by DCM will become more personalized and lead to earlier interventions [ 35 – 37 ]. Thus, a larger and prospective study combining all these factors should be performed to evaluate the efficacy between the treatment of HF and outcomes in children with DCM. Limitations Several limitations were included in this study. Assessment of cardiac functions is often difficult and a lack of objectivity can occur due to non-cooperation of young children. Echocardiography was usually not performed by the same doctor. This may have introduced error measurements into the research. This just was a small-sample and retrospective research in one single center and therefore prone to biases and limitations. Further larger-sample and prospective researches are warranted to verify our conclusions. Finally, selection bias was existed due to the nature of the retrospective study. Conlusions It was concluded that severe HF at diagnosis was related to a higher risk of death. The result shows that improvement of HF may be a primary goal of therapy and can potentially increase the survival in children with DCM. Further prospective studies are warranted to evaluate the efficacy between the treatment of HF and outcomes in children with DCM. Abbreviations DCM Dilated cardiomyopathy HF Heart failure LVEDD left ventricular end-diastolic dimension SDs standard deviations LVESD left ventricular end-systolic dimension LVEDPWT left ventricular end-diastolic posterior wall thickness LVEDST left ventricular end-diastolic septal thickness LVEF:left ventricular ejection fraction LVFS left ventricular fractional shortening BMI body mass index HR Hazard ratios CI confidence intervals ACEI Angiotensin-converting enzyme inhibitors ARNI neprilysin inhibitor MRA mineralocorticoid receptor antagonist SGLT2 sodium-glucose co-transporter-2 PAB pulmonary artery banding. Declarations ACKNOWLEDGEMENTS Thanks for the help of all the working partners of the first Ward of Pediatrics in our hospital and http://zscore.chboston.org for z-score calculation during the preparation of this manuscript. The authors thank Dr Dev Sooranna of Imperial College London for editing the manuscript. AUTHOR CONTRIBUTIONS CC contributed to study design and drafted the article. DS, SQ, YH and WZ contributed to statistical analysis, BY, YH and DL collected data. YP contributed to the concept of the research and the edited manuscript. All authors took part in drafting article and had their permission for publication. FUNDING This study was funded by a grant from the Scientific Research Project of Guangxi Health Planning Commission (Grant no. Z20210993). Availability of data and materials All data generated or analyzed during this study are included in this published article and its supplementary information files. Ethics approval and consent to participate This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (NO. 2022(KY-E-007)) and carried out in accordance with the principles of the Declaration of Helsinki (as revised in 2013). Informed consent was obtained from their legal guardians. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. References SE L, YM L, A A-K, ED A, AI D, MD E, DT H, KY L, JF P, JD W et al : Cardiomyopathy in Children: Classification and Diagnosis: A Scientific Statement From the American Heart Association . Circulation 2019, 140 (1):e9-e68. JA T, AM L, SD C, LA S, EJ O, S C, J M, GF C, PR L, D H et al : Incidence, causes, and outcomes of dilated cardiomyopathy in children . JAMA 2006, 296 (15):1867–1876. 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Perri G, Filippelli S, Adorisio R, Iacobelli R, Iodice F, Testa G, Paglietti MG, D'Amario D, Massetti M, Amodeo A: Left ventricular assist device as destination therapy in cardiac end-stage dystrophinopathies: Midterm results . The Journal of thoracic and cardiovascular surgery 2017, 153 (3):669–674. Motonaga KS, Dubin AM: Cardiac resynchronization therapy for pediatric patients with heart failure and congenital heart disease: a reappraisal of results . Circulation 2014, 129 (18):1879–1891. Pincott ES, Ridout D, Brocklesby M, McEwan A, Muthurangu V, Burch M: A randomized study of autologous bone marrow-derived stem cells in pediatric cardiomyopathy . The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 2017, 36 (8):837–844. Tsirka AE, Trinkaus K, Chen SC, Lipshultz SE, Towbin JA, Colan SD, Exil V, Strauss AW, Canter CE: Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation . J Am Coll Cardiol 2004, 44 (2):391–397. Verdonschot JAJ, Merlo M, Dominguez F, Wang P, Henkens M, Adriaens ME, Hazebroek MR, Masè M, Escobar LE, Cobas-Paz R et al : Phenotypic clustering of dilated cardiomyopathy patients highlights important pathophysiological differences . Eur Heart J 2021, 42 (2):162–174. Kayvanpour E, Sedaghat-Hamedani F, Amr A, Lai A, Haas J, Holzer DB, Frese KS, Keller A, Jensen K, Katus HA et al : Genotype-phenotype associations in dilated cardiomyopathy: meta-analysis on more than 8000 individuals . Clinical research in cardiology: official journal of the German Cardiac Society 2017, 106 (2):127–139. Hauser JA, Demyanets S, Rusai K, Goritschan C, Weber M, Panesar D, Rindler L, Taylor AM, Marculescu R, Burch M et al : Diagnostic performance and reference values of novel biomarkers of paediatric heart failure . Heart 2016, 102 (20):1633–1639. Additional Declarations No competing interests reported. Supplementary Files dataSevereHeartFailureandOutcomesin121ChildrenWithDilatedCardiomyopathy.xls Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-1352003","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":85722789,"identity":"1240c5be-00a4-4c5d-a059-fb738632e013","order_by":0,"name":"Cheng Chen","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Cheng","middleName":"","lastName":"Chen","suffix":""},{"id":85722790,"identity":"4ac14f18-5c12-4ba9-bd4e-9167fea7d4e7","order_by":1,"name":"Danyan Su","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Danyan","middleName":"","lastName":"Su","suffix":""},{"id":85722791,"identity":"6e21996c-29f9-4da6-8bcb-08ee6a046ddb","order_by":2,"name":"Suyuan Qin","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Suyuan","middleName":"","lastName":"Qin","suffix":""},{"id":85722793,"identity":"d1b47d69-2828-4a31-9531-6a9be697486c","order_by":3,"name":"Bingbing Ye","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bingbing","middleName":"","lastName":"Ye","suffix":""},{"id":85722794,"identity":"5ded7b9a-f888-4d1e-a9e3-9ffd0a839077","order_by":4,"name":"Yanyun Huang","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yanyun","middleName":"","lastName":"Huang","suffix":""},{"id":85722796,"identity":"9567171f-df7a-41fc-8105-b79b4b848bcf","order_by":5,"name":"Weiying Zhao","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Weiying","middleName":"","lastName":"Zhao","suffix":""},{"id":85722797,"identity":"1d315bd6-6708-4f7e-9ce4-559246c9495b","order_by":6,"name":"Yuqin Huang","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuqin","middleName":"","lastName":"Huang","suffix":""},{"id":85722800,"identity":"f0fd331d-3533-4eb2-8c4e-dc16fb5d2c03","order_by":7,"name":"Dongli Liu","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dongli","middleName":"","lastName":"Liu","suffix":""},{"id":85722803,"identity":"256eb02b-f587-4a8e-a169-7e46e39f7483","order_by":8,"name":"Yusheng Pang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwElEQVRIiWNgGAWjYBCDBH5m5sMPSNMi2c6WZkCaFoPzPAoSRCk1Zz97+DVvW12e8WEeBgOGGptoglose/LSrHnbDhebHeY98IDhWFpuAyEtBgdyzIx52w4kbjvMl2DA2HCYCC3n34C01CVubuYxkCBOy40c48e8bcyJG5iJ1WI5440Z45xzhxNnHAYGcgIxfjHnzzH+8KasLrG///DhBx9qbIhwGAMDmxQPjJdASDlUC/PHH8SoHAWjYBSMgpELAP4JQCUK6KknAAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yusheng","middleName":"","lastName":"Pang","suffix":""}],"badges":[],"createdAt":"2022-02-12 04:29:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1352003/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1352003/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":18575148,"identity":"214e344e-5f1b-49f4-99e9-22cb77d2bde3","added_by":"auto","created_at":"2022-02-24 15:59:47","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":114270,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analysis in severe and mild heart failure. The time to death was shorter for children with severe HF, compared with those having mild HF. Log-rank testing P values for survival at 12, 24, and 60 months after diagnosis of dilated cardiomyopathy were \u0026lt;0.001.\u003c/p\u003e","description":"","filename":"fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1352003/v1/2dd5f063e54c1e490aa6021a.jpg"},{"id":21771973,"identity":"56c04a1a-403f-4e7b-9d9f-7376a23d14d4","added_by":"auto","created_at":"2022-05-23 12:14:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1324928,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1352003/v1/d7c5e74d-4e1a-4dfe-adc7-785646b7f0b3.pdf"},{"id":18575149,"identity":"6914c233-f5a3-4268-ab87-b3c0c2d8498f","added_by":"auto","created_at":"2022-02-24 15:59:47","extension":"xls","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":165888,"visible":true,"origin":"","legend":"","description":"","filename":"dataSevereHeartFailureandOutcomesin121ChildrenWithDilatedCardiomyopathy.xls","url":"https://assets-eu.researchsquare.com/files/rs-1352003/v1/7d130735137dbd1768aff58a.xls"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eSevere Heart Failure and Outcomes in 121 Children With Dilated Cardiomyopathy: A Single-Center Retrospective Study from Southwest China\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDilated cardiomyopathy (DCM) is a progressive and serious disorder of the heart muscle which is characterized by the dilation of the left ventricle accompanied by a reduction of systolic function[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. DCM is diagnosed in 0.57 cases per 100 000 children /year in the United States and has a 20% mortality rate at 1 year and a 56% mortality rate at 4 years[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although the prognosis of children with DCM have increased in the past 20 years[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], the management of patients with this condition needed to be more targeted and precise in order to raise long-term prognosis.\u003c/p\u003e \u003cp\u003eHeart failure (HF) is a severe complication of DCM and a major cause of heart transplantation or sudden death in children with DCM [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Improvement of HF can reverse cardiac histologic remodeling and increase the prognosis of DCM[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. With the release of the European Society of Cardiology and American College of Cardiology Guidelines for HF in 2021, the management of HF has become more standardized and effective[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, we performed a novel analysis comparing children with severe HF who were classified as ROSS/NYHA class III or class IV to those with mild HF who were classified as ROSS/NYHA class I or class II. We hypothesized that severe HF is related to poor prognosis in children with DCM.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Subjects\u003c/h2\u003e \u003cp\u003eChildren aged\u0026thinsp;\u0026le;\u0026thinsp;18 years with a diagnosis of DCM admitted to the First Affiliated Hospital of Guangxi Medical University between March 2003 and September 2021 were enrolled into the study. The exclusion criteria included ① congenital heart disease, arrhythmia cardiomyopathy, ischemic heart disease, cardiac valve disease and hypertensive heart disease; ② DCM with known etiology, such as drug-induced cardiomyopathy and inherited metabolic cardiomyopathy such as primary carnitine deficiency.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDefinitions\u003c/h2\u003e \u003cp\u003eDiagnosis of DCM was indicated by a left ventricular end-diastolic dimension (LVEDD) of more than two standard deviations (SDs) above normal for the individual\u0026rsquo;s body surface area (or \u003cem\u003ez\u003c/em\u003e-score for age\u0026thinsp;\u0026gt;\u0026thinsp;2) and a left ventricular ejection fraction (LVEF) or left ventricular fractional shortening (LVFS) of lower than 2 standard deviations for healthy children of the same age (or \u003cem\u003ez\u003c/em\u003e-score for age\u0026thinsp;\u0026lt;\u0026thinsp;2). Severe HF was defined as an improved ROSS scoring criteria (\u0026ge;\u0026thinsp;7score)[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] or NYHA class III/IV and mild HF was defined as an improved ROSS scoring criteria (༜7score) or NYHA class I/II.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy Methods\u003c/h2\u003e \u003cp\u003eGeneral data involved age, race, sex and body mass index (BMI), HF at diagnosis, duration of symptoms, duration of stay in hospital, multiple hospitalizations (\u0026ge;\u0026thinsp;2 visits), admission to the intensive care unit, family history of DCM, heart rate at diagnosis, systolic and diastolic blood pressure measurements at diagnosis, echocardiographic measurements z-scores, medications, follow-up periods and outcomes. The patients were classified into either a severe and or a mild HF group based on the severity of HF. The primary adverse event was death.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData analyses were performed employing SPSS software (version 24.0 for Windows, SPSS, Inc., Chicago, Illinois). Data are presented either as means or percentages. Continuous variates were compared using Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e test (for normally distributed data) or Wilcoxon rank sum test (for non-normally distributed data), and categorical variates were compared with chi-square tests. Kaplan\u0026ndash;Meier plots were established, and log-rank statistics were employed to evaluate survival differences at specific time points of 12, 24 and 60 months after enrollment as well as overall survival. Cox regression was performed to confirm the factors independently related to worse outcomes to reduce selection bias among children involved in the study. Hazard ratios (HR) and 95% confidence intervals (95% CI) were used to present the data. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was identified statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eClinical Characteristics\u003c/h2\u003e \u003cp\u003eThere were 121 DCM patients in this cohort. The mean age of the 121 patients was 118.5\u0026thinsp;\u0026plusmn;\u0026thinsp;63.0 months. Of these, 81 (67.8%) patients were grouped as severe HF and 39 (32.2%) were placed in a mild HF group. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the demographic information, clinical indicators, echocardiographic characteristics, medications used at the time of cardiomyopathy diagnosis, time period of follow-up and the outcomes of patients who were classified as severe HF compared with those who were classified as mild HF. There were no significant differences between the groups when compared by race, duration of symptoms, duration in the first hospitalization, multiplicity of hospitalizations, family history of DCM, BMI, heart rate and systolic blood pressure. Nevertheless, patients with severe HF were older, more likely to be male, have lower systolic pressure, be admitted to the intensive care unit and be treated with β-blockers, loop diuretics, spironolactone and digoxin. Patient with severe HF were more likely to have lower LVEF z-scores, larger systolic and diastolic LV dimensional z-scores, and more likely to suffer from aortic and tricuspid regurgitations.\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\u003eDemographics, clinical indicators, echocardiographic measurement, drug use, time of follow-up and Outcomes of the patients in this study.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSevere HF (n\u0026thinsp;=\u0026thinsp;82)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMild HF (n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD), m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118.5\u0026thinsp;\u0026plusmn;\u0026thinsp;63.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129.5\u0026thinsp;\u0026plusmn;\u0026thinsp;64.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95.4\u0026thinsp;\u0026plusmn;\u0026thinsp;53.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69 (57.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (63.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (43.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.865\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (47.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (46.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (51.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZhuang\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (48.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (43.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of symptoms, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD), m\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.899\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration in first hospitalization, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD), d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.342\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple hospitalizations, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (42.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (47.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (30.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdmission to intensive care unit, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (43.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (54.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (20.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of dilated cardiomyopathy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (9.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.388\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.089\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart rate at admission, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e113.4\u0026thinsp;\u0026plusmn;\u0026thinsp;21.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114.2\u0026thinsp;\u0026plusmn;\u0026thinsp;20.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e111.7\u0026thinsp;\u0026plusmn;\u0026thinsp;24.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.574\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esystolic blood pressure at admission, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97.2\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e104.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ediastolic blood pressure at admission, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.417\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eMedications at diagnosis N (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACEI/ARNI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (85.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 (86.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (82.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.512\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (30.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (36.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (17.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.038\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoop diuretic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114 (94.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (98.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (84.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpironolactone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e111 (91.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 (95.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (84.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDigoxin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114 (94.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (98.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (84.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntravenous inotropes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (50.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (56.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (38.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eLV echocardiographic z scores, (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEDD z scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVESD z scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.035\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEDPWT z scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEDST z scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.679\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLV fractional shortening z scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.411\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLV ejection fraction z scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMitral regurgitation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80 (96.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (97.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (94.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.439\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic regurgitation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (12.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (12.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid regurgitation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 85.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (90.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (76.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.049\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary regurgitation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (35.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (39.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (28.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.245\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up times\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.5\u0026thinsp;\u0026plusmn;\u0026thinsp;42.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.4\u0026thinsp;\u0026plusmn;\u0026thinsp;40.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43.2\u0026thinsp;\u0026plusmn;\u0026thinsp;45.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEvents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83 (68.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (79.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (46.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eHF, heart failure; LVEDD, left ventricular end-diastolic dimension; LVESD, left ventricular end-systolic dimension; LVEDPWT, left ventricular end-diastolic posterior wall thickness; LVEDST, left ventricular end-diastolic septal thickness; ACEI, angiotensin-converting enzyme inhibitors; ARNI, angiotensin II receptor blocker neprilysin inhibitor.\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\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe median follow-up time was 24.4 months for patients with severe HF and 43.2 months for patients with mild HF (P\u0026thinsp;\u0026lt;\u0026thinsp;0.024). Of the 82 children with severe HF, 50 (60.9% at 12months), 56 (68.3% at 24 months), 65 (79.2% at 60 months) and 65 (79.2%, overall) died, whereas among the 39 children with mild HF, 9 (23.1% at 12 months), 12 (30.8% at 24 months), 18 (46.1% at 60 months) and 18 (46.1% overall) died (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared with those with mild HF, the time to death was shorter for children with severe HF (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Cox regression analysis was employed to confirm the factors related to the overall probability of death (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Severe HF increased the risk of death in unmodulated and in all modulated Cox regression analyses. This relationship was not weakened after modulating for various factors. However, after modulating for use of loop diuretics, severe HF was independently related to a higher risk of death (hazard ratio [HR] 2.27; 95% Cl, 1.28\u0026ndash;4.03 in model 6). In model 6, use of loop diuretics was related to a decreased risk of death (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, hazard ratio [HR] 0.074; 95% Cl, 0.006\u0026ndash;0.876, p\u003c0.039).\u003c/p\u003e \u003cp\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\u003eMultivariate Cox regression modeling of severe heart failure versus mild heart failure.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVariates\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModel 1 (n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModel 2 (n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eModel 3 (n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eModel 4 (n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eModel 5 (n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eModel 6 (n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"10\" rowspan=\"11\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHeart Failure (severe vs mild)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e2.516 (1.488\u0026ndash;4.255)\u003c0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e2.614 (1.538\u0026ndash;4.440)\u003c0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e2.741 (1.603\u0026ndash;4.686)\u003c0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e2.625 (1.524\u0026ndash;4.620)\u003c0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e2.512 (1.448\u0026ndash;4.357)\u003c0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e2.274 (1.280\u0026ndash;4.038)\u003c0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.998 (0.995\u0026ndash;1.002) 0.329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.998 (0.995\u0026ndash;1.002) 0.460\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.999 (0.996\u0026ndash;1.003) 0.743\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.999 (0.995\u0026ndash;1.003) 0.558\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1.000 (0.995\u0026ndash;1.004) 0.947\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.330 (0.854\u0026ndash;2.073) 0.207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.318 (0.847\u0026ndash;2.051) 0.221\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.283 (0.821\u0026ndash;2.006) 0.273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.766 (0.475\u0026ndash;1.237) 0.276\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHeart Rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.005 (0.995\u0026ndash;1.016) 0.335\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.004 (0.993\u0026ndash;1.015) 0.445\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1.005 (0.993\u0026ndash;1.016) 0.418\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLVEF z scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.949 (0.857\u0026ndash;1.052) 0.320\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.935 (0.838\u0026ndash;1.043) 0.225\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eACEI/ARNI (yes vs no )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1.214 (0.569\u0026ndash;2.588) 0.615\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ-blockers (yes vs no )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1.035 (0.551\u0026ndash;1.942) 0.915\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLoop diuretics (yes vs no )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.074 (0.006\u0026ndash;0.876) 0.039\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpirolactone (yes vs no )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2.338 (0.756\u0026ndash;7.232) 0.140\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDigoxin (yes vs no )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2.421 (0.406\u0026ndash;16.912) 0.311\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntravenous inotropes (yes vs no )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.943 (0.577\u0026ndash;1.542) 0.815\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eHazard ratios (95% CIs) and P values were used to show data. Variates were employed according to the statistics in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) or prognostic indicator. Model 1 is a one-variable Cox regression analysis with heart failure (HF) variable (severe HF vs mild HF). Model 2 modulates for age. Model 3 ulteriorly modulates for sex (male/female) besides the variates in Model 2. Model 4 ulteriorly modulates for heart rate besides the variates in Model 3. Model 5 ulteriorly modulates for LV ejection fraction z score besides the covariates employed in Model 4. Model 6 ulteriorly modulates for drug (including either ACEI or ARNI, and beta blockers, loop diuretics, spironolactone, digoxin and intravenous inotropes) besides the variates employed in Model 5.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe study demonstrates that children with DCM and severe HF at diagnosis were older, more likely to be male, have lower systolic blood pressure measurements, be admitted to the ICU and be treated with β-blockers, loop diuretics, spironolactone and digoxin. They are also more likely to have larger diastolic LV end-diastolic dimensional z-scores and poorer LV function. Compared with children with DCM and mild HF, those with DCM and severe HF at diagnosis were at a higher risk of death. Severe HF was related to an accumulated risk of death. These associations were not affected by sex, age at diagnosis, heart rate, ventricular function and use of medication.\u003c/p\u003e \u003cp\u003eThese results are similar to those found in a study by Rusconi [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. They showed similar results with respect to survival between family-associated DCM and idiopathic DCM after modulation for other variates. However, HF, older age, and larger left ventricular end-diastolic dimension (LVEDD) at diagnosis were independently related to increased risks of the major adverse events of heart transplantation or death. In a retrospective analysis, HF with NYHA III/IV were significantly associated with overall death risk[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. A meta-analysis of 57 researches of medication adherence interventions for HF treatment from adults found an obvious association between improvement of HF and a decrease of mortality[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These findings lend support to the idea that an improvement in HF may be a key goal for DCM therapy.\u003c/p\u003e \u003cp\u003eAngiotensin-converting enzyme inhibitors (ACEI) is the cornerstone of HF treatment and can significantly improve cardiac remodeling. The beneficial effects of ACEI for HF in children with DCM have been proven in previous studies[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. One prospective and large-sample study which included 5,955 adult patients with DCM and LVEF\u0026thinsp;\u0026lt;\u0026thinsp;40% also confirmed that use of ACEI was related to the recovery of the LVEF coupled with an improvement of HF at 3 years of follow-up[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In a European survey between pediatric HF and ACEI use patterns conducted between January and May 2015, ACEI appeared to be essential in pediatric HF treatment strategies[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Nowadays, the angiotensin II receptor blocker, neprilysin inhibitor (ARNI), is more effective when compared with ACEI, and this drug has now been recommended to be the preferred treatment in patients with HF[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn children with DCM and HF, elevated heart rate is often accompanied by worsening HF. Thus, the heart rate may be a target for HF treatment. Beta blockers can reduce heart rate. Three meta-analysis on the use of beta-blockers for congestive HF in children showed that children with congestive HF might benefit from treatment with these drugs[\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Additionally, ivabradine is a novel drug which can reduce the heart rate. A study randomized 116 patients diagnosed with DCM and class II to IV HF. In this study, the heart rate was reduced by \u0026ge;\u0026thinsp;20% from baseline without leading to symptoms or bradycardia were more likely to occur in the patients taking ivabradine rather than taking the placebo. This reduction was accompanied with a significant increase in the LVEF, an improvement of the cardiac function as well as in the quality of life[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Another adult study also showed that the reduction of heart rate in the ivabradine group could improve the prognosis of HF[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, loop diuretics was related to a decreased risk of death. Diuretics are also another important treatment for HF. A meta-analysis of 14 studies with 525 participants of the use of diuretic in HF suggested that these were able to reduce mortality and retard progression of HF [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In a study of 25,345 elder patients with HF, patients with loop diuretics as a discharge prescription had a better clinical improvement comparing with those not taking loop diuretics[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. One study included 108 children and showed that an increase of loop diuretic responsiveness during the first 72 hours of treatment was accompanied by shorter length of hospital stays and a decrease of inpatient deaths or use of mechanical circulatory support[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In addition to loop diuretics, a mineralocorticoid receptor antagonist (MRA), such as spironolactone, which can also have a diuretic effect, is fundamental during the long-term management of HF[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere are several emerging treatments for HF in children with DCM. In a meta-analysis study, sodium-glucose co-transporter-2 (SGLT2) inhibitors were shown to reduce all-cause and cardiovascular death in patients with HF [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], and these drugs are recommended to be the preferred choice of treatment in patients with HF[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Pulmonary artery banding (PAB) treatment, as a new indication for end-stage DCM in pediatric patients, has also been shown to be safe and effective[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Left ventricular mechanical assist can be indicated as destination therapy for end-stage DCM[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Cardiac pacemaker can be an effective tool for treating HF, especially in patients who have a complete left bundle branch block[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Cardiac stem cell therapy is yet another feasible and safe treatment in children with DCM and HF, and can improve left ventricular function[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. If none of the above methods work, heart transplantation could be considered as a last resort[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs we have already confirmed that severe HF is related to a higher risk of death in children with DCM, so therapies that improve HF can increase survival. Through a more comprehensive understanding of DCM, especially with respect to the genetics of DCM and the potential of finding new early markers and treatment for HF, it is envisaged that the treatment of HF caused by DCM will become more personalized and lead to earlier interventions [\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Thus, a larger and prospective study combining all these factors should be performed to evaluate the efficacy between the treatment of HF and outcomes in children with DCM.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eSeveral limitations were included in this study. Assessment of cardiac functions is often difficult and a lack of objectivity can occur due to non-cooperation of young children. Echocardiography was usually not performed by the same doctor. This may have introduced error measurements into the research. This just was a small-sample and retrospective research in one single center and therefore prone to biases and limitations. Further larger-sample and prospective researches are warranted to verify our conclusions. Finally, selection bias was existed due to the nature of the retrospective study.\u003c/p\u003e"},{"header":"Conlusions","content":"\u003cp\u003eIt was concluded that severe HF at diagnosis was related to a higher risk of death. The result shows that improvement of HF may be a primary goal of therapy and can potentially increase the survival in children with DCM. Further prospective studies are warranted to evaluate the efficacy between the treatment of HF and outcomes in children with DCM.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDCM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDilated cardiomyopathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHeart failure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVEDD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eleft ventricular end-diastolic dimension\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSDs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003estandard deviations\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVESD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eleft ventricular end-systolic dimension\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVEDPWT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eleft ventricular end-diastolic posterior wall thickness\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVEDST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eleft ventricular end-diastolic septal thickness LVEF:left ventricular ejection fraction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVFS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eleft ventricular fractional shortening\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHazard ratios\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence intervals\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eACEI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAngiotensin-converting enzyme inhibitors\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eARNI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eneprilysin inhibitor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emineralocorticoid receptor antagonist\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSGLT2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esodium-glucose co-transporter-2\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePAB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epulmonary artery banding.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThanks for the help of all the working partners of the first Ward of Pediatrics in our hospital and http://zscore.chboston.org for z-score calculation during the preparation of this manuscript. The authors thank Dr Dev Sooranna of Imperial College London for editing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCC contributed to study design and drafted the article. DS, SQ, YH and WZ contributed to statistical\u0026nbsp;analysis, BY, YH and DL collected data. YP contributed to the concept of the research and the edited manuscript. All authors took part in drafting article and had their permission for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by a\u0026nbsp;grant from\u0026nbsp;the Scientific Research Project of Guangxi Health Planning Commission (Grant no. Z20210993).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (NO. 2022(KY-E-007)) and carried out in accordance with the principles of the Declaration of Helsinki (as revised in 2013). \u0026nbsp;Informed consent was obtained from their legal guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSE L, YM L, A A-K, ED A, AI D, MD E, DT H, KY L, JF P, JD W \u003cem\u003eet al\u003c/em\u003e: \u003cb\u003eCardiomyopathy in Children: Classification and Diagnosis: A Scientific Statement From the American Heart Association\u003c/b\u003e. Circulation 2019, \u003cb\u003e140\u003c/b\u003e(1):e9-e68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJA T, AM L, SD C, LA S, EJ O, S C, J M, GF C, PR L, D H \u003cem\u003eet al\u003c/em\u003e: \u003cb\u003eIncidence, causes, and outcomes of dilated cardiomyopathy in children\u003c/b\u003e. JAMA 2006, \u003cb\u003e296\u003c/b\u003e(15):1867\u0026ndash;1876.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNugent AW, Daubeney PE, Chondros P, Carlin JB, Cheung M, Wilkinson LC, Davis AM, Kahler SG, Chow CW, Wilkinson JL \u003cem\u003eet al\u003c/em\u003e: \u003cb\u003eThe epidemiology of childhood cardiomyopathy in Australia\u003c/b\u003e. 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Heart 2016, \u003cb\u003e102\u003c/b\u003e(20):1633\u0026ndash;1639.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Dilated cardiomyopathy, heart failure, children, management, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-1352003/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1352003/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eHeart failure is a common complication in children with dilated cardiomyopathy. The aim of this study was to determine whether severe heart failure at diagnosis was related to poor outcomes in children with dilated cardiomyopathy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe analyzed medical data from 121 children with dilated cardiomyopathy in our hospital from 2003 to 2021. The children were grouped by the degree of heart failure. Cox regression analysis was performed to confirm whether severe heart failure was associated with poor outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThere were 121 patients with dilated cardiomyopathy in this research. The mean age of the 121 patients was 118.5\u0026thinsp;\u0026plusmn;\u0026thinsp;63.0 months. Of these patients, 81 (67.8%) were sorted into a severe heart failure group and 39 (32.2%) were placed into a mild heart failure group. A comparison between the two groups showed that patients with severe heart failure were older and more likely to be male, have lower systolic blood pressure measurements, be admitted to the intensive care unit and be treated with β-blockers, loop diuretics, spironolactone and digoxin. In addition, they had larger systolic and diastolic left ventricular end-diastolic dimensional and lower left ventricular ejection fractional z-scores as well as being more prone to aortic and tricuspid regurgitations (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in all cases). After adjusting for age, sex, heart rate, left ventricular ejection fraction z-scores and drug, severe heart failure was found to be independently associated with an increased risk of death (hazard ratio [HR] 2.27; P\u0026thinsp;\u0026lt;\u0026thinsp;0.005).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eSevere heart failure at diagnosis was related to a greater risk of death in children with dilated cardiomyopathy. Further prospective studies are warranted to evaluate the efficacy between the treatment undertaken for heart failure and outcomes in children with dilated cardiomyopathy.\u003c/p\u003e","manuscriptTitle":"Severe Heart Failure and Outcomes in 121 Children With Dilated Cardiomyopathy: A Single-Center Retrospective Study from Southwest China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-02-24 15:59:45","doi":"10.21203/rs.3.rs-1352003/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e93efd24-9d27-42d5-b6d5-5f87d783a069","owner":[],"postedDate":"February 24th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-05-23T12:14:21+00:00","versionOfRecord":[],"versionCreatedAt":"2022-02-24 15:59:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1352003","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1352003","identity":"rs-1352003","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}