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D-dimer is a biomarker of coagulation and fibrinolytic system activation in response to the hypercoagulable state of the body. The research aimed to analyze the value of D-dimer in the prognosis of patients with dilated cardiomyopathy (DCM). Patients admitted to our center for the first time with DCM were enrolled consecutively. The clinical characteristics variables were obtained from the electronic medical record system, and the prognostic information was obtained using telephone return visits and a review of repeated hospitalization records. Univariate and multivariate Cox regression was used to explore the association of D-dimer with all-cause mortality. Smooth curve fitting, threshold saturation effect analysis, and subgroup analysis were performed. Ultimately, 534 patients were included. After a follow-up of the enrolled patients, 485 patients obtained prognostic information, of which 159 died from all causes, and the main cause of death was heart failure (89/159), the sudden death accounted for about 17%. The independent positive association between D-dimer and all-cause mortality remained unchanged in both unadjusted and adjusted Cox regression models. In the fully adjusted model, each standard deviation increase in D-dimer was associated with a 14% increase in all-cause mortality (HR = 1.14; 95% CI: 1.02 ~ 1.27; P < 0.05). Curve fitting and threshold effect analysis showed an inflection point in the relationship between D-dimer and all-cause mortality (non-linear test: P = 0.03). When D-dimer was equal to 362ng/ml, HR = 1; and as the value increased, the risk of all-cause mortality increased by 34.7% for every 2-fold increase in D-dimer gradually (HR = 1.347; 95% CI: 1.069 ~ 1.697; P = 0.012). In subgroup analysis, D-dimer and BMI had a significant interaction on all-cause mortality, with a significantly increased risk of all-cause mortality in subjects with BMI ≥ 25 kg/m 2 (HR = 1.99; 95% CI: 1.34 ~ 2.97; P < 0.01). The ROC curve showed that D-dimer was a good predictor of all-cause mortality, and the areas under the curve at 1-, 3-, and 5-year were 0.71, 0.64, and 0.59, respectively. In addition, D-dimer improved the predictive performance of the MAGGIC heart failure score in patients with DCM. D-dimer is not only independently associated with all-cause mortality in DCM patients, but also has good predictive value, suggesting that D-dimer may be an early and useful marker for improving the management of DCM patients., (© 2024. The Author(s).)

Introduction: In children with myocarditis or dilated cardiomyopathy (DCM) on extracorporeal membrane oxygenation (ECMO) for cardiogenic shock, it is often necessary to decompress the left heart to minimize distension and promote myocardial recovery. We compare outcomes in those who underwent balloon atrial septostomy (BAS) versus direct left atrial (LA) drainage for left heart decompression in this population., Methods: Retrospective study of the Extracorporeal Life Support Organization (ELSO) multicenter registry of patients ≤ 18 years with myocarditis or DCM on ECMO who underwent LA decompression. Descriptive and univariate statistics assessed association of patient factors with decompression type. Multivariable logistic regression sought independent associations with outcomes., Results: 369 pediatric ECMO runs were identified. 52% myocarditis, 48% DCM, overall survival 74%. 65% underwent BAS and 35% LA drainage. Patient demographics including age, weight, gender, race/ethnicity, diagnosis, pre-ECMO pH, mean airway pressure, and arrest status were similar. 89% in the BAS group were peripherally cannulated onto ECMO, versus 3% in the LA drainage group ( p < .001). On multivariable analysis, LA drainage (OR 3.96; 95% CI, 1.47-10.711; p = .007), renal complication (OR 2.37; 95% CI, 1.41-4.01; p = .001), cardiac complication (OR 3.14; 95% CI, 1.70-5.82; p < .001), and non-white race/ethnicity (OR 1.75; 95% CI, 1.04-2.94; p = .035) were associated with greater odds of mortality. There was a trend toward more episodes of pulmonary hemorrhage in BAS ( n = 17) versus LA drainage group ( n = 3), p = .08. Comparing only those with central cannulation, LA drainage group was more likely to be discontinued from ECMO due to recovery (72%) versus the BAS group (48%), p = .032., Conclusions: In children with myocarditis or DCM, there was a three times greater likelihood for mortality with LA drainage versus BAS for LA decompression. When adjusted for central cannulation groups only, there was better recovery in the LA drainage group and no difference in mortality. Further prospective evaluation is warranted., Competing Interests: Declaration of conflicting interestsDavid LS Morales is a consultant for Abbott, Berlin Heart, CorMatrix/Azyio, Medtronic, and SynCardia Systems. Ravi R. Thiagarajan is supported by a grant from US Department of Defense Clinical Trial Award #W81XWH2210301, Callaghan Family Chair in Cardiac Critical Care. Farhan Zafar is employed as Procurement Surgeon for TransMedics, Inc.

Background: Dilated cardiomyopathy (DCM) is a major cause of heart failure and heart transplantation. Recently, some studies have reported that the autoimmune response in myocardial cells might be related to the pathogenesis of DCM. The CD247 gene has been previously found to be involved in autoimmune disease. Therefore, our study aimed to clarify the hypothesis that there is a certain linkage between polymorphisms of the CD247 gene and the triggering of DCM risk., Methods: In the present study, two single nucleotide polymorphisms (SNPs) of the CD247 gene, rs12141731 and rs858543, were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 355 DCM patients and 404 age- and sex-matched controls., Results: Pearson's chi-squared test for the CD247 gene revealed that SNP rs858543 (p = 0.001, OR = 0.72, 95% CI = (0.588-0.882), but not SNP rs12141731, was associated with DCM in the Chinese Han population. Haplotype analysis revealed that the CC haplotype was associated with increased DCM susceptibility, while CT was a protective haplotype. Cox multivariate survival analysis indicated that the rs858543 TT genotype (HR: 0.608, 95% CI = 0.402-0.921, p = 0.019) was an independent multivariate predictor for longer overall survival in DCM patients. CD247 mRNA expression levels were significantly decreased in DCM patients (p = 0.02)., Conclusions: Our study suggested that a polymorphism in the CD247 gene may be a risk factor for DCM in the Chinese Han population., Trial Registration: ChiCTR2000029701., (© 2024. The Author(s).)

Aim: Liver damage frequently occurs in patients with cardiovascular (CV) disease and is associated with adverse clinical outcomes. The associations of liver damage with cardiac structure/function measures and the risk of adverse CV events in patients with dilated cardiomyopathy (DCM) are poorly known., Methods: We retrospectively enrolled consecutive patients with DCM undergoing cardiac magnetic resonance imaging (MRI). In addition to standard cardiac assessment, iron-corrected T1 mapping was also assessed in the liver. Cross-sectional associations between hepatic T1-time and cardiac structure and function were examined accounting for potential confounders. Longitudinal associations between hepatic T1-time and the risk of hospitalization for HF or CV death were also assessed., Results: Overall, 120 stable patients with established DCM were included in the study (mean age 54.7 years, 26 % women). The mean hepatic iron-corrected T1-time was 563±73 ms. In linear regression analyses, measures of left atrial structure (LA maximal volume, p = 0.035, LA minimal volume=0.012), interventricular septum thickness (p = 0.026), and right ventricular ejection fraction (p = 0.005) were significantly associated with greater hepatic T1-time. Over a mean follow-up of 4.5 ± 1.8 years, 32 (27 %) died or were hospitalized for HF at a rate of 6.7 per 100 person-year. Higher hepatic iron-corrected T1-time was independently associated with a higher risk of adverse events (adjusted-hazard ratio 1.71, 95 % confidence interval: 1.14-2.56, p = 0.009). Patients with a hepatic T1-time ≥563 ms had a higher risk of CV events (log-rank p = 0.03)., Conclusion: Among stable patients with DCM, higher hepatic iron-corrected T1-time is associated with worse cardiac size and function and with higher rates of hospitalization for HF or CV death., Condensed Abstract: Limited data exist regarding the clinical value of hepatic T1-time in patients with dilated cardiomyopathy (DCM) undergoing cardiac Magnetic Resonance imaging (MRI). We found that higher hepatic iron-corrected T1-time is associated with worse cardiac size and function, even after accounting for clinical confounders. Over a mean follow-up of 4.5 ± 1.8 years, higher hepatic iron-corrected T1-time was independently associated with a higher risk of hospitalization for heart failure or cardiovascular death. Among stable patients with DCM, the evaluation of liver tissue by cardiac MRI may provide useful clinical information for CV risk stratification., Competing Interests: Conflict of Interest Disclosures The authors declare they have no conflict of interest, (Copyright © 2024. Published by Elsevier B.V.)

Cardiac magnetic resonance (CMR) feature-tracking (FT) has an important diagnostic role in non-ischemic dilated cardiomyopathy (NIDCM). To date, the relationship between whole-heart myocardial mechanics by CMR and early primary outcomes in NIDCM has not been elucidated. patients with NIDCM were eligible for this study. CMR-FT was used to analyze whole-heart myocardial mechanics. The primary outcomes were a composite of heart failure (HF) death, heart transplantation (HT), and hospitalization for HF worsening (WHF) after 1-year since diagnosis. 98 patients were included. During a 1-year follow-up, a worse prognosis occurred in 32 patients (30 hospitalizations for WHF, 8 deaths, and 3 HT). The left ventricular (LV) global longitudinal systolic strain (GLS), left ventricular global circumferential strain (LV GCS), strains of right ventricle and both atria were significantly reduced in patients with events vs. those without (GLS - 8.0 ± 3.4 vs. - 12.1 ± 4.5, p < 0.001; GCS - 13.0 ± 6.4 vs. - 18.3 ± 7.1, p < 0.001; right ventricular (RV) GLS - 12.1 ± 4.9 vs. - 17.4 ± 6.4, p < 0.001; left atrial longitudinal strain 7.5 ± 3.8 vs. 15.1 ± 12.3, p < 0.001; right atrial longitudinal strain 11.0 ± 6.7 vs. 17.2 ± 8.0, p < 0.001). Left ventricular ejection fraction (LVEF) was significantly higher in patients with better prognosis (22.7 ± 8.7 vs. 33.56 ± 10.4, p < 0.001). Multivariate regression analysis revealed LV GLS as an independent predictor of a worse prognosis (OR 0.787, CI 95% 0.697-0.890, p < 0.001). reduction of LV GLS showed the strongest predictive value for the composite outcome of WHF, HT, and HF death., (© 2024. The Author(s).)

Objectives: The prognostic value of left ventricular (LV) papillary muscle anomalies in dilated cardiomyopathy (DCM) patients is unclear. The objective of this study was to evaluate the prognostic significance of LV papillary muscle anomalies in DCM patients using cardiac magnetic resonance (CMR)., Methods: 369 DCM patients who underwent CMR at two Chinese medical facilities from January 2019 to June 2023 were retrospectively and consecutively included in total. The various features of the LV papillary muscles were taken into consideration: thickness, attachment, supernumerary papillary muscles, angles, and signal intensity. The end-systolic signal hypointensity of both papillary muscles in early post-contrast cine CMR images was identified as Dark-Paps. Major adverse cardiac events (MACEs) were assessed, and all patients were followed up., Results: 119 patients (32.2 %) had Dark-Paps and 141 patients (38.2 %) experienced MACE during a median follow-up of 22 months. According to Kaplan-Meier curve analysis, patients who had Dark-Paps had a lower survival rate free from MACE (log-rank, p < 0.001). Dark-Paps maintained an independent predictor of MACE in a multivariate model that included left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) extent (HR: 3.49; p < 0.001). Furthermore, adding Dark-Paps to the multivariate model greatly enhanced the prognostic role of endpoint events (C-statistic improvement: 0.652-0.777, Delong test: p < 0.001)., Conclusion: Dark-Paps is a potent independent indicator of major adverse cardiac events in dilated cardiomyopathy patients. In addition, Dark-Paps can provide additional prognostic value over the multivariable baseline clinical model., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Restrictive cardiomyopathy is rare and is generally associated with worse clinical outcomes compared to other cardiomyopathies. Ventricular assist device (VAD) support for these children is seldom applied and often hampered by the surgical difficulties., Methods: All paediatric (<19 years) patients with a restricted cardiomyopathy supported by a VAD from the EUROMACS database were included and compared to patients with a dilated cardiomyopathy (retrospective database analyses). Participating centres were retrospectively contacted to provide additional detailed echo and Swan Ganz measurements to analyse the effect of VAD support on pulmonary artery pressure and right ventricular function., Results: Forty-four paediatric VAD-supported patients diagnosed with restricted cardiomyopathy were included, with a median age at implantation of 5.0 years. Twenty-six of the 44 patient with a restricted cardiomyopathy survived to transplantation (59.1%), 16 died (36.4%) and 2 are still on ongoing VAD support (4.5%) after a median duration of support of 95.5 days (interquartile range 33.3-217.8). Transplantation probability after 1 and 2 years of VAD support in patients with a restricted cardiomyopathy were comparable to patients with a dilated cardiomyopathy (52.3% vs 51.4% and 59.5% vs 60.1%, P = 0.868). However, mortality probability was higher in the restricted cardiomyopathy cohort (35.8% vs 17.0% and 35.8% vs 19.0%, P = 0.005). Adverse event rates were high (cerebrovascular accident in 31.8%, pump thrombosis in 29.5%, major bleeding 25.0%, eventual biventricular support in 59.1%). In the atrially cannulated group, cerebrovascular accident and pump thrombosis occurred in twice as much patients (21.1% vs 40.0%, P = 0.595 and 15.8% vs 40.0%, P = 0.464; probably non-significant due to the small numbers). Pulmonary arterial pressures improved after implantation of a VAD, and 6 patients who were initially labelled as ineligible due to pulmonary hypertension could eventually be transplanted., Conclusions: VAD support in children with a restricted cardiomyopathy is rarely performed. Mortality and adverse event rates are high. On the other hand, survival to cardiac transplantation was 59.1% with all patients surviving the 1st 30 days after cardiac transplantation. Pulmonary arterial pressures improved while on support, potentially making cardiac transplantation a viable option for previously ineligible children., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Myocardial work (MW) derived from pressure-strain loops is a novel non-invasive tool to assess left ventricular (LV) function, incorporating global longitudinal strain (GLS) by speckle tracking echocardiography and non-invasively assessed blood pressure. Studies on the role of MW in dilated cardiomyopathy (DCM) are still limited. Therefore, the aim of this study was to evaluate the potential value of MW for predicting adverse outcomes in patients with DCM. 116 consecutive patients with DCM who underwent heart catheterization were retrospectively recruited from June 2009 to July 2014. 34 patients (30%) met the composite endpoints for major adverse cardiac events (MACE) of cardiac transplantation, need for implantable cardioverter-defibrillator (ICD) therapy, heart failure hospitalization and all-cause mortality. Patients with DCM were followed up for a mean of 5.1 years (IQR: 2.2-9.1 years). Global work index (GWI) and global constructive work (GCW) were not only independent predictors but also provided incremental predictive values (Integrated discrimination improvement [IDI] > 0) of MACE in multivariate Cox models. Furthermore, Patients with GWI < 788 mm Hg% (HR 5.46, 95%CI 1.66-17.92, p = 0.005) and GCW < 1,238 mm Hg% (HR 4.46, 95%CI 1.53-12.98, p = 0.006) had higher risks of MACE. GWI and GCW assessed by strain imaging echocardiography may have an additional value beyond LV-EF and GLS for predicting adverse outcomes in DCM., (© 2024. The Author(s).)

Background: The prognostic value of follow-up cardiovascular magnetic resonance (CMR) in dilated cardiomyopathy (DCM) patients is unclear. We aimed to investigate the prognostic value of cardiac function, structure, and tissue characteristics at mid-term CMR follow-up., Methods: The study population was a prospectively enrolled cohort of DCM patients who underwent guideline-directed medical therapy with baseline and follow-up CMR, which included measurement of biventricular volume and ejection fraction, late gadolinium enhancement, native T1, native T2, and extracellular volume. During follow-up, major adverse cardiac events (MACE) were defined as a composite endpoint of cardiovascular death, heart transplantation, and heart-failure readmission., Results: Among 235 DCM patients (median CMR interval: 15.3 months; interquartile range: 12.5-19.2 months), 54 (23.0%) experienced MACE during follow-up (median: 31.2 months; interquartile range: 20.8-50.0 months). In multivariable Cox regression, follow-up CMR models showed significantly superior predictive value than baseline CMR models. Stepwise multivariate Cox regression showed that follow-up left ventricular ejection fraction (LVEF; hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.91-0.96; p < 0.001) and native T1 (HR, 1.01; 95% CI, 1.00-1.01; p = 0.030) were independent predictors of MACE. Follow-up LVEF ≥ 40% or stable LVEF < 40% with T1 ≤ 1273 ms indicated low risk (annual event rate < 4%), while stable LVEF < 40% and T1 > 1273 ms or LVEF < 40% with deterioration indicated high risk (annual event rate > 15%)., Conclusions: Follow-up CMR provided better risk stratification than baseline CMR. Improvements in the LVEF and T1 mapping are associated with a lower risk of MACE., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic value of left ventricular (LV) myocardial trabecular complexity on cardiovascular magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown. This study aimed to evaluate the prognostic value of LV myocardial trabecular complexity using fractal analysis in patients with DCM., Methods: Consecutive patients with DCM who underwent CMR between March 2017 and November 2021 at two hospitals were prospectively enrolled. The primary endpoints were defined as the combination of all-cause death and heart failure hospitalization. The events of cardiac death alone were defined as the secondary endpoints.LV trabeculae complexity was quantified by measuring the fractal dimension (FD) of the endocardial border based on fractal geometry on CMR. Cox proportional hazards regression and Kaplan-Meier survival analysis were used to examine the association between variables and outcomes. The incremental prognostic value of FD was assessed in nested models., Results: A total of 403 patients with DCM (49.31 ± 14.68 years, 69% male) were recruited. After a median follow-up of 43 months (interquartile range, 28-55 months), 87 and 24 patients reached the primary and secondary endpoints, respectively. Age, heart rate, New York Heart Association functional class >II, N-terminal pro-B-type natriuretic peptide, LV ejection fraction, LV end-diastolic volume index, LV end-systolic volume index, LV mass index, presence of late gadolinium enhancement, global FD, LV mean apical FD, and LV maximal apical FD were univariably associated with the outcomes (all P < 0.05). After multivariate adjustment, LV maximal apical FD remained a significant independent predictor of outcome [hazard ratio = 1.179 (1.116, 1.246), P < 0.001]. The addition of LV maximal apical FD in the nested models added incremental prognostic value to other common clinical and imaging risk factors (all <0.001; C-statistic: 0.84-0.88, P < 0.001)., Conclusion: LV maximal apical FD was an independent predictor of the adverse clinical outcomes in patients with DCM and provided incremental prognostic value over conventional clinical and imaging risk factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Acute myocarditis has been genetically linked to dilated cardiomyopathy (DCM), but the clinical significance remains uncertain. We investigated the prevalence and long-term prognosis of DCM and heart failure (HF) among unselected patients hospitalized with acute myocarditis and their first-degree relatives compared with an age- and sex-matched cohort., Methods: This was an observational study utilizing the Danish nationwide registries, where all patients with a first-time myocarditis diagnosis from 1995 to 2018 were identified and matched (on birth year and sex) with 10 controls from the general population., Results: Totally 3176 patients with acute myocarditis and 31 760 controls were included (median age, 49.8 [Q1-Q3, 32.5-70.2] years; 35.6% female). At baseline, patients with myocarditis had a higher prevalence of DCM (7 [0.2%] versus 8 [0.0%]) and HF (336 [10.6%] versus 695 [2.2%]) than controls; P <0.0001 for both. Patients with myocarditis more often had siblings with DCM (12 [0.4%] versus 17 [0.05%]) or HF (36 [1.1%] versus 89 [0.3%]); P <0.0001, odds ratios 7.09 (3.38-14.85) and 2.92 (1.25-6.80), respectively, whereas parental DCM and HF did not differ among patients with myocarditis and controls. Patients with myocarditis had greater 20-year incidence of DCM, HF, and all-cause mortality (0.5% [0.3%-0.9%], 15% [13%-17%], and 47% [44%-50%]) compared with controls (0.06% [0.03%-0.11%], 6.8% [6.4%-7.3%], and 34% [33%-35%]; P <0.0001). Having a first-degree relative with DCM or HF was associated with increased long-term mortality among the patients with myocarditis (hazard ratio, 1.40 [1.11-1.77]) but not among the controls (hazard ratio, 0.90 [0.81-1.01]; P difference =0.0008)., Conclusions: Acute myocarditis aggregates with DCM within families, where it carries a worsened prognosis. A differential association between parents and siblings (with sibling preponderance) could suggest that additional environmental factors are important for myocarditis development even in predisposed individuals., Competing Interests: Disclosures Dr Lakdawala reported having received modest consulting incomes from Akros, Bristol Myers Squibb, Pfizer, Cytokinetics, and Tenaya; and research support from Pfizer and Bristol Myers Squibb. Dr Schou reported having received lecture fees from Novartis, Novo Nordisk, AstraZeneca, and Boehringer Ingelheim. Dr Gustafsson reported having received consulting fees from Abbott, Pfizer, AstraZeneca, Alnylam, and Bayer; and speaker fees from Novartis. Dr Køber reported having received speaker’s honorarium from Bayer, Novartis, AstraZeneca, and Boehringer Ingelheim. Dr Torp-Pedersen reported having received grants from Bayer and Novo Nordisk. The other authors report no conflicts.

Background: Accurate prediction and assessment of myocardial fibrosis (MF) and adverse cardiovascular events (MACEs) are crucial in patients with dilated cardiomyopathy (DCM). Several studies indicate that galectin-3 (gal-3) as a promising prognostic predictor in patients with DCM., Methods: A comprehensive search was conducted in PubMed, EMBASE, the Cochrane Library, and Web of Science for relevant studies up to August 2023. The hazard ratios (HRs) of gal-3 for MACEs in DCM patients, and for MACEs in LGE(+) versus LGE(-) groups, were evaluated. Statistical analysis was performed using STATA SE 14.0 software., Results: Seven studies, encompassing 945 patients, met the eligibility criteria. In DCM patients, abnormally elevated gal-3 levels were indicative of an increased MACEs risk (HR = 1.10, 95% CI [1.00-1.21], I 2 = 65.7%, p  = 0.008). Compared with the LGE(-) group, the level of gal-3 in LGE(+) group was higher (HR = 1.12, 95% CI [1.05-1.19], I 2 = 31.4%, p  = 0.233), and the combination of gal-3 and LGE significantly improved the prediction of MACEs. Sensitivity analysis confirmed the robustness of all results., Conclusions: This study's findings suggest that elevated gal-3 levels significantly correlate with increased MACE risk in DCM, highlighting its potential as a biomarker. However, significant heterogeneity among studies necessitates further research to ascertain gal-3's predictive and diagnostic value in DCM prognosis, particularly in conjunction with LGE., Prospero Id: CRD42023471199., Competing Interests: The authors declare there are no competing interests., (©2024 Xiong and Zhang.)

Pediatric cardiomyopathies (CM) are rare and challenging to diagnose due to the complex and mixed phenotypes. With the advent of next-generation sequencing (NGS), variants in several genes associated with CM have been identified, such as Troponin C (TnC), encoded by the TNNC1 gene. De novo variants in TNNC1 have been associated with different types of CM, including dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The American College of Medical Genetics and Genomics recently added TNNC1 to their recommended list of genes for reporting secondary findings. In this study, we report a de novo variant, c.100G>C (p.Gly34Arg) in the TNNC1 gene identified in three siblings with a diagnosis of severe DCM causing infant death for one of the siblings and stillbirth in the other two pregnancies. The identification of the same de novo variant in all affected siblings is suggestive of germline mosaicism in this family.

Objective: The study objective was to evaluate the short- and long-term outcomes of patients with ischemic cardiomyopathy after surgical ventricular restoration and to identify risk factors related to poor results., Methods: Between August 2002 and April 2016, 62 patients affected by ischemic cardiomyopathy underwent surgical left ventricular restoration at our unit. Patients' mean age at operation was 63 years (39-79 years). Mean ejection fraction was 29.6%. The Surgical Treatment for Ischemic Heart Failure trial criteria have been used as indications for surgery. Fifty-seven patients (91%) received surgical myocardial revascularization. Mitral valve repair was performed in 39 patients (63%). The surgical technique consisted of the classic Dor operation or a different approach reducing the equatorial diameter of the left ventricle and avoiding the use of a patch. The data were analyzed retrospectively for perioperative results and short- and long-term clinical outcomes., Results: One patient died of noncardiac causes within 30 days (1.6%). All-cause death occurred in 36 patients (58%) during follow-up (0.6-14.7 years; median follow-up time, 7.02 years), of whom 15 died of cardiac causes. Age, need for preoperative intra-aortic balloon pump, reduction less than 35% of postoperative left ventricular end-diastolic and end-systolic volumes, type of surgical technique, and ejection fraction less than 25% were identified as risk factors for late cardiac mortality. Perioperative levosimendan administration and presence of preoperative moderate to severe mitral regurgitation influenced early and intermediate-term outcomes, but no statistical relevance on long-term results was demonstrated., Conclusions: Patients with ischemic dilative cardiomyopathy have favorable short- and long-term outcomes after ventricular restoration. Age, preoperative ejection fraction less than 25%, inadequate left ventricular surgical reverse remodeling, and type of surgical technique negatively affect long-term survival., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy, and it often has a poor outcome. Sex differences in the prognosis of patients with DCM remain controversial. The present meta-analysis aimed to investigate whether sex plays a role in the outcome of patients with DCM and to provide real-world information on these potential sex differences for physicians and patients.We searched the PubMed, Cochrane, and EMBASE databases for published cohort studies up to February 16, 2020 that reported sex-specific prognostic outcomes (e.g., all-cause mortality; sudden cardiac death (SCD) ) in patients with DCM.Finally, 5 clinical cohort studies with a total of 5,709 patients were included. The results showed that males with DCM had a higher risk of all-cause mortality than females (HR: 1.61, 95% CI: 1.36~1.90; P < 0.00001). Next, the included studies were divided into short-term (< 5 years) and long-term (≥ 5 years) outcome groups by follow-up duration. Males showed a higher risk of all-cause mortality in both subgroups (< 5 years, HR: 1.59, 95% CI: 1.13~2.23; P = 0.008; ≥ 5 years, HR: 1.65, 95% CI: 1.33~2.05; P < 0.00001). In addition, the risks of SCD (HR: 1.80, 95% CI: 1.63~2.61; P = 0.002) and cardiovascular mortality in males (HR: 1.67, 95% CI: 1.25~2.23; P = 0.0005) were higher than those in females.The evidence from the published studies suggested that compared with females, males with DCM had an increased risk of all-cause mortality, cardiovascular mortality, and SCD.

Objective: Patients with dilated cardiomyopathy (DCM) and severely reduced left ventricular ejection fractions (LVEFs) are at very high risks of experiencing adverse cardiac events. A machine learning (ML) method could enable more effective risk stratification for these high-risk patients by incorporating various types of data. The aim of this study was to build an ML model to predict adverse events including all-cause deaths and heart transplantation in DCM patients with severely impaired LV systolic function., Methods: One hundred and eighteen patients with DCM and severely reduced LVEFs (<35%) were included. The baseline clinical characteristics, laboratory data, electrocardiographic, and cardiac magnetic resonance (CMR) features were collected. Various feature selection processes and classifiers were performed to select an ML model with the best performance. The predictive performance of tested ML models was evaluated using the area under the curve (AUC) of the receiver operating characteristic curve using 10-fold cross-validation., Results: Twelve patients died, and 17 patients underwent heart transplantation during the median follow-up of 508 days. The ML model included systolic blood pressure, left ventricular end-systolic and end-diastolic volume indices, and late gadolinium enhancement (LGE) extents on CMR imaging, and a support vector machine was selected as a classifier. The model showed excellent performance in predicting adverse events in DCM patients with severely reduced LVEF (the AUC and accuracy values were 0.873 and 0.763, respectively)., Conclusions: This ML technique could effectively predict adverse events in DCM patients with severely reduced LVEF., Advances in Knowledge: The ML method has superior ability in risk stratification in severe DCM patients.

Background Cardiac fibrosis plays a crucial role in the pathogenesis of dilated cardiomyopathy (DCM). HE4 (human epididymis protein 4) is a secretory protein expressed in activated fibroblasts that exacerbates tissue fibrosis. In the present study, we investigated the clinical utility of HE4 measurement in patients with DCM and its pathophysiological role in preclinical experiments in vivo and in vitro. Methods and Results We measured serum HE4 levels of 87 patients with DCM. Endomyocardial biopsy expressed severe fibrosis only in the high HE4 group ( P <0.0001). Echocardiography showed that left ventricular end-diastolic diameter tends to decrease over time (58±7.3 to 51±6.6 mm; P <0.0001) in the low HE4 group (<59.65 pmol/L [median value]). HE4 was significantly associated with risk reduction of mortality and cardiovascular hospitalization in multivariate Cox model. In vivo, HE4 was highly expressed in kidney and lung tissue of mouse, and scarcely expressed in heart. In genetically induced DCM mouse model, HE4 expression increased in kidney but not in heart and lung. In vitro, supernatant from HE4-transfected human embryonic kidney 293T cells enhanced transdifferentiation of rat neonatal fibroblasts and increased expression of fibrosis-related genes, and this was accompanied by the activation of extracellular signal-regulated kinase signaling in cardiac fibroblasts. Treatment with an inhibitor of upstream signal of extracellular signal-regulated kinase or a neutralizing HE4 antibody canceled the profibrotic properties of HE4. Conclusions HE4 functions as a secretory factor, activating cardiac fibroblasts, thereby inducing cardiac interstitial fibrosis. HE4 could be a promising biomarker for assessing ongoing fibrosis and a novel therapeutic target in DCM. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr; Unique identifier: UMIN000043062.

Introduction: Prenatal recognition of dilated aortic root is extremely rare and there are significant challenges in counselling these patients. The primary aim of this case series is to describe the prevalence, associations and outcome of dilated ascending aorta diagnosed during fetal life., Methods: This is a retrospective cohort study from two tertiary fetal cardiology centres. Dilated ascending aorta was defined as gestation-specific standard deviation > 1.96 at some point during gestation., Results: Sixteen infants were live born and underwent postnatal echocardiography. Prenatally suspected bicuspid aortic valve (BAV) (n = 6) was confirmed in 5 cases (83%) postnatally. Thirteen children have been followed up for a period of minimum one year. No connective tissue disease was found., Conclusions: Prenatal dilated ascending aorta is a rare finding (0.06%). It is associated with BAV in 37% of cases and extracardiac abnormalities in 15.7%. Nuchal translucency measurement was >3.5 in 13% of cases. Connective tissue disease was not diagnosed postnatally. This is the largest prenatal cohort with dilated ascending aorta and postnatal outcomes to date. We showed a postnatal persistence of ascending aortic dilatation in 43% of babies. In the absence of extra-cardiac abnormalities, medium term outcome appears good but postnatal surveillance of aortic dilation is required., (© 2021 John Wiley & Sons Ltd.)

Background: Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought to characterize the clinical and genetic characteristics in patients with myocarditis ≤18 years of age to predict outcome., Methods: A cohort of 42 patients (Genetics in Pediatric Myocarditis) with biopsy-proven myocarditis underwent genetic testing with targeted panel sequencing of cardiomyopathy-associated genes. Genetics in Pediatric Myocarditis patients were divided into subgroups according to the phenotype of dilated cardiomyopathy (DCM) at presentation, resulting in 22 patients without DCM (myocarditis without phenotype of DCM) and 20 patients with DCM (myocarditis with phenotype of DCM)., Results: Myocarditis with phenotype of DCM patients (median age 1.4 years) were younger than myocarditis without phenotype of DCM patients (median age 16.1 years; P <0.001) and were corresponding to heart failure-like and coronary syndrome-like phenotypes, respectively. At least one likely pathogenic/pathogenic variant was identified in 9 out of 42 patients (22%), 8 of them were heterozygous, and 7 out of 9 were in myocarditis with phenotype of DCM. Likely pathogenic/pathogenic variants were found in genes validated for primary DCM ( BAG3, DSP, LMNA, MYH7, TNNI3, TNNT2 , and TTN ). Rare variant enrichment analysis revealed significant accumulation of high-impact disease variants in myocarditis with phenotype of DCM versus healthy individuals ( P =0.0003). Event-free survival was lower ( P =0.008) in myocarditis with phenotype of DCM patients compared with myocarditis without phenotype of DCM and primary DCM., Conclusions: We report heterozygous likely pathogenic/pathogenic variants in biopsy-proven pediatric myocarditis. Myocarditis patients with DCM phenotype were characterized by early-onset heart failure, significant enrichment of likely pathogenic/pathogenic variants, and poor outcome. These phenotype-specific and age group-specific findings will be useful for personalized management of these patients. Genetic evaluation in children newly diagnosed with myocarditis and DCM phenotype is warranted.

Importance: Truncating variants in the gene encoding filamin C (FLNCtv) are associated with arrhythmogenic and dilated cardiomyopathies with a reportedly high risk of ventricular arrhythmia., Objective: To determine the frequency of and risk factors associated with adverse events among FLNCtv carriers compared with individuals carrying TTN truncating variants (TTNtv)., Design, Setting, and Participants: This cohort study recruited 167 consecutive FLNCtv carriers and a control cohort of 244 patients with TTNtv matched for left ventricular ejection fraction (LVEF) from 19 European cardiomyopathy referral units between 1990 and 2018. Data analyses were conducted between June and October, 2020., Main Outcomes and Measures: The primary end point was a composite of malignant ventricular arrhythmia (MVA) (sudden cardiac death, aborted sudden cardiac death, appropriate implantable cardioverter-defibrillator shock, and sustained ventricular tachycardia) and end-stage heart failure (heart transplant or mortality associated with end-stage heart failure). The secondary end point comprised MVA events only., Results: In total, 167 patients with FLNCtv were studied (55 probands [33%]; 89 men [53%]; mean [SD] age at baseline evaluation, 43 [18] years). For a median follow-up of 20 months (interquartile range, 7-60 months), 29 patients (17.4%) reached the primary end point (19 patients with MVA and 10 patients with end-stage heart failure). Eight (44%) arrhythmic events occurred among individuals with baseline mild to moderate left ventricular systolic dysfunction (LVSD) (LVEF = 36%-49%). Univariable risk factors associated with the primary end point included proband status, LVEF decrement per 10%, ventricular ectopy (≥500 in 24 hours) and myocardial fibrosis detected on cardiac magnetic resonance imaging. The LVEF decrement (hazard ratio [HR] per 10%, 1.83 [95% CI, 1.30-2.57]; P < .001) and proband status (HR, 3.18 [95% CI, 1.12-9.04]; P = .03) remained independent risk factors on multivariable analysis (excluding myocardial fibrosis and ventricular ectopy owing to case censoring). There was no difference in freedom from MVA between FLNCtv carriers with mild to moderate or severe (LVEF ≤35%) LVSD (HR, 1.29 [95% CI, 0.45-3.72]; P = .64). Carriers of FLNCtv with impaired LVEF at baseline evaluation (n = 69) had reduced freedom from MVA compared with 244 TTNtv carriers with similar baseline LVEF (for mild to moderate LVSD: HR, 16.41 [95% CI, 3.45-78.11]; P < .001; for severe LVSD: HR, 2.47 [95% CI, 1.04-5.87]; P = .03)., Conclusions and Relevance: The high frequency of MVA among patients with FLNCtv with mild to moderate LVSD suggests that higher LVEF values than those currently recommended should be considered for prophylactic implantable cardioverter-defibrillator therapy in FLNCtv carriers.

Voltage dependent anion channel 2 (VDAC2) is an outer mitochondrial membrane porin known to play a significant role in apoptosis and calcium signaling. Abnormalities in calcium homeostasis often leads to electrical and contractile dysfunction and can cause dilated cardiomyopathy and heart failure. However, the specific role of VDAC2 in intracellular calcium dynamics and cardiac function is not well understood. To elucidate the role of VDAC2 in calcium homeostasis, we generated a cardiac ventricular myocyte-specific developmental deletion of Vdac2 in mice. Our results indicate that loss of VDAC2 in the myocardium causes severe impairment in excitation-contraction coupling by altering both intracellular and mitochondrial calcium signaling. We also observed adverse cardiac remodeling which progressed to severe cardiomyopathy and death. Reintroduction of VDAC2 in 6-week-old knock-out mice partially rescued the cardiomyopathy phenotype. Activation of VDAC2 by efsevin increased cardiac contractile force in a mouse model of pressure-overload induced heart failure. In conclusion, our findings demonstrate that VDAC2 plays a crucial role in cardiac function by influencing cellular calcium signaling. Through this unique role in cellular calcium dynamics and excitation-contraction coupling VDAC2 emerges as a plausible therapeutic target for heart failure., (© 2021. The Author(s).)

Background: Stem cell therapy (SCT) has been proposed as an alternative treatment for dilated cardiomyopathy (DCM), nonetheless its effectiveness remains debatable., Objectives: To assess the effectiveness and safety of SCT in adults with non-ischaemic DCM., Search Methods: We searched CENTRAL in the Cochrane Library, MEDLINE, and Embase for relevant trials in November 2020. We also searched two clinical trials registers in May 2020., Selection Criteria: Eligible studies were randomized controlled trials (RCT) comparing stem/progenitor cells with no cells in adults with non-ischaemic DCM. We included co-interventions such as the administration of stem cell mobilizing agents. Studies were classified and analysed into three categories according to the comparison intervention, which consisted of no intervention/placebo, cell mobilization with cytokines, or a different mode of SCT. The first two comparisons (no cells in the control group) served to assess the efficacy of SCT while the third (different mode of SCT) served to complement the review with information about safety and other information of potential utility for a better understanding of the effects of SCT., Data Collection and Analysis: Two review authors independently screened all references for eligibility, assessed trial quality, and extracted data. We undertook a quantitative evaluation of data using random-effects meta-analyses. We evaluated heterogeneity using the I² statistic. We could not explore potential effect modifiers through subgroup analyses as they were deemed uninformative due to the scarce number of trials available. We assessed the certainty of the evidence using the GRADE approach. We created summary of findings tables using GRADEpro GDT. We focused our summary of findings on all-cause mortality, safety, health-related quality of life (HRQoL), performance status, and major adverse cardiovascular events., Main Results: We included 13 RCTs involving 762 participants (452 cell therapy and 310 controls). Only one study was at low risk of bias in all domains. There were many shortcomings in the publications that did not allow a precise assessment of the risk of bias in many domains. Due to the nature of the intervention, the main source of potential bias was lack of blinding of participants (performance bias). Frequently, the format of the continuous data available was not ideal for use in the meta-analysis and forced us to seek strategies for transforming data in a usable format. We are uncertain whether SCT reduces all-cause mortality in people with DCM compared to no intervention/placebo (mean follow-up 12 months) (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.54 to 1.31; I² = 0%; studies = 7, participants = 361; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection in people with DCM (data could not be pooled; studies = 7; participants = 361; very low-certainty evidence). We are uncertain whether SCT improves HRQoL (standardized mean difference (SMD) 0.62, 95% CI 0.01 to 1.23; I² = 72%; studies = 5, participants = 272; very low-certainty evidence) and functional capacity (6-minute walk test) (mean difference (MD) 70.12 m, 95% CI -5.28 to 145.51; I² = 87%; studies = 5, participants = 230; very low-certainty evidence). SCT may result in a slight functional class (New York Heart Association) improvement (data could not be pooled; studies = 6, participants = 398; low-certainty evidence). None of the included studies reported major adverse cardiovascular events as defined in our protocol. SCT may not increase the risk of ventricular arrhythmia (data could not be pooled; studies = 8, participants = 504; low-certainty evidence). When comparing SCT to cell mobilization with granulocyte-colony stimulating factor (G-CSF), we are uncertain whether SCT reduces all-cause mortality (RR 0.46, 95% CI 0.16 to 1.31; I² = 39%; studies = 3, participants = 195; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection (studies = 1, participants = 60; very low-certainty evidence). SCT may not improve HRQoL (MD 4.61 points, 95% CI -5.62 to 14.83; studies = 1, participants = 22; low-certainty evidence). SCT may improve functional capacity (6-minute walk test) (MD 140.14 m, 95% CI 119.51 to 160.77; I² = 0%; studies = 2, participants = 155; low-certainty evidence). None of the included studies reported MACE as defined in our protocol or ventricular arrhythmia. The most commonly reported outcomes across studies were based on physiological measures of cardiac function where there were some beneficial effects suggesting potential benefits of SCT in people with non-ischaemic DCM. However, it is unclear if this intermediate effects translates into clinical benefits for these patients. With regard to specific aspects related to the modality of cell therapy and its delivery, uncertainties remain as subgroup analyses could not be performed as planned, making it necessary to wait for the publication of several studies that are currently in progress before any firm conclusion can be reached., Authors' Conclusions: We are uncertain whether SCT in people with DCM reduces the risk of all-cause mortality and procedural complications, improves HRQoL, and performance status (exercise capacity). SCT may improve functional class (NYHA), compared to usual care (no cells). Similarly, when compared to G-CSF, we are also uncertain whether SCT in people with DCM reduces the risk of all-cause mortality although some studies within this comparison observed a favourable effect that should be interpreted with caution. SCT may not improve HRQoL but may improve to some extent performance status (exercise capacity). Very low-quality evidence reflects uncertainty regarding procedural complications. These suggested beneficial effects of SCT, although uncertain due to the very low certainty of the evidence, are accompanied by favourable effects on some physiological measures of cardiac function. Presently, the most effective mode of administration of SCT and the population that could benefit the most is unclear. Therefore, it seems reasonable that use of SCT in people with DCM is limited to clinical research settings. Results of ongoing studies are likely to modify these conclusions., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Temporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003-2015., Methods: DCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003-2007 (Period 1, n = 2029), 2008-2011 (Period 2, n = 3363), 2012-2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry., Results: Over the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p < 0.0001). Device (implantable cardioverter defibrillator and/or cardiac resynchronization) therapy increased by 30% over time (mean 11.6%, 12.3%, 15.1%, p < 0.0001). The event rates for mortality, and hospitalization were consistently decreasing over calendar periods (p < 0.0001 for all), whereas transplantation rate was stable. More advanced physical symptoms correlated with an increased risk of a composite outcome over time (p = 0.0043)., Conclusions: From 2003 until 2015, we observed declining mortality and hospitalizations in DCM, paralleled by a continuous change in both demographic profile and therapy in the DCM population in Sweden, towards a less affected phenotype.

Background: Risk stratification for ventricular arrhythmias (VA) and sudden death in nonischemic dilated cardiomyopathy (DCM) remains suboptimal., Objectives: The goal of this study was to provide an improved risk stratification algorithm for VA and sudden death in DCM., Methods: This was a retrospective cohort study of consecutive patients with DCM who underwent cardiac magnetic resonance with late gadolinium enhancement (LGE) at 2 tertiary referral centers. The combined arrhythmic endpoint included appropriate implantable cardioverter-defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, and sudden death., Results: In 1,165 patients with a median follow-up of 36 months, LGE was an independent and strong predictor of the arrhythmic endpoint (hazard ratio: 9.7; p < 0.001). This association was consistent across all strata of left ventricular ejection fraction (LVEF). Epicardial LGE, transmural LGE, and combined septal and free-wall LGE were all associated with heightened risk. A simple algorithm combining LGE and 3 LVEF strata (i.e., ≤20%, 21% to 35%, >35%) was significantly superior to LVEF with the 35% cutoff (Harrell's C statistic: 0.8 vs. 0.69; area under the curve: 0.82 vs. 0.7; p < 0.001) and reclassified the arrhythmic risk of 34% of patients with DCM. LGE-negative patients with LVEF 21% to 35% had low risk (annual event rate 0.7%), whereas those with high-risk LGE distributions and LVEF >35% had significantly higher risk (annual event rate 3%; p = 0.007)., Conclusions: In a large cohort of patients with DCM, LGE was found to be a significant, consistent, and strong predictor of VA or sudden death. Specific high-risk LGE distributions were identified. A new clinical algorithm integrating LGE and LVEF significantly improved the risk stratification for VA and sudden death, with relevant implications for implantable cardioverter-defibrillator allocation., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic significance of serial echocardiography and its rate of change in children with dilated cardiomyopathy (DCM) is incompletely defined., Methods: We retrospectively analysed up to 4 serial echocardiograms. Associations between mortality/transplant and echocardiographic parameters over time and between outcomes and the rate of change of echocardiographic parameters were analysed. Estimation of patient-specific intercepts and slopes was done using linear regression models., Results: Fifty-seven DCM children were studied (50% male; median age, 0.6 year; average follow-up, 2.1 ± 2.4 years). The median time to transplant or death was 2.0 years. Increased left ventricular (LV) diastolic (LVEDD) and systolic (LVESD) dimensions and myocardial performance index (MPI) were associated with increased mortality and transplant risk. Increased LV ejection fraction, mitral E-deceleration time, right ventricular (RV) fractional area change, and tricuspid annular plane systolic excursion were associated with reduced mortality and transplant risk. Transplant/mortality likelihood increased by 41.6% and 19.8% for each unit increase in LVEDD and LVESD z scores, respectively (LVEDD: hazard ratio [HR], 1.416; 95% confidence interval [CI], 1.285-1.560; P < 0.001; LVESD: HR, 1.198; 95% CI, 1.147-1.251; P < 0.001). A higher monthly change in LVESD z score increased transplant/mortality likelihood by 85.6% (HR, 1.856; 95% CI, 1.572-2.191; P = 0.015). Greater changes in mitral E/e' (HR, 0.707; 95% CI, 0.636-0.786; P < 0.001) and RV MPI (HR, 0.412; 95% CI, 0.277-0.613; P < 0.001) were associated with reduced mortality and transplant risk., Conclusions: LV and RV systolic and diastolic dimensions and function over time and their rate of change are associated with risk for transplant and mortality in childhood DCM. Serial changes in these parameters may be useful to predict clinical outcomes., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Chagas' disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients., Competing Interests: The authors have declared that no competing interests exist.

Background: A considerable number of non-ischemic dilated cardiomyopathy (NDCM) patients had been found to have normalized left ventricular (LV) size and systolic function with tailored medical treatments. Accordingly, we aimed to evaluate if strain parameters assessed by cardiovascular magnetic resonance (CMR) feature tracking (FT) analysis could predict the NDCM recovery., Methods: 79 newly diagnosed NDCM patients who underwent baseline and follow-up CMR scans were enrolled. Recovery was defined as a current normalized LV size and systolic function evaluated by CMR., Results: Among 79 patients, 21 (27%) were confirmed recovered at a median follow-up of 36 months. Recovered patients presented with faster heart rates (HR) and larger body surface area (BSA) at baseline (P < 0.05). Compared to unrecovered patients, recovered pateints had a higher LV apical radial strain divided by basal radial strain (RS api/bas ) and a lower standard deviation of time to peak radial strain in 16 segments of the LV (SD16-TTPRS). According to a multivariate logistic regression model, RS api/bas (P = 0.035) and SD16-TTPRS (P = 0.012) resulted as significant predictors for differentiation of recovered from unrecovered patients. The sensitivity and specificity of RS api/bas and SD16-TTPRS for predicting recovered conditions were 76%, 67%, and 91%, 59%, with the area under the curve of 0.75 and 0.76, respectively. Further, Kaplan Meier survival analysis showed that patients with RS api/bas  ≥ 0.95% and SD16-FTPRS ≤ 111 ms had the highest recovery rate (65%, P = 0.027)., Conclusions: RS api/bas and CMR SD16-TTPRS may be used as non-invasive parameters for predicting LV recovery in NDCM. This finding may be beneficial for subsequent treatments and prognosis of NDCM patients. Registration number: ChiCTR-POC-17012586.

The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased LV contractility with HCM risk. A polygenic risk score explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that polygenic risk score may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.

Fragmented QRS (fQRS) is an easily evaluated noninvasive parameter in electrocardiograms (ECGs) for predicting cardiac adverse events. Our study aimed to evaluate whether fQRS could be used as a risk factor to predict a major adverse cardiac event (MACE) in children with idiopathic dilated cardiomyopathy (DCM). Our retrospective study enrolled 63 patients aged ≤ 19 years who were newly diagnosed with idiopathic DCM at Samsung Medical Center from 2003 to 2014, and followed up until December 2018. Demographic data, ECGs, and echocardiography were reviewed and analyzed for their possible links with adverse outcomes. The median age was 14.0 months and the median length of follow-up was 65.0 months. Age, QRS duration, and ejection fraction in M-mode at diagnosis were significantly different between the fQRS and non-fQRS groups (P = 0.026; P = 0.001; and P = 0.020). Significant difference between the fQRS and non-fQRS groups was found in patients with a MACE (P = 0.016, odd ratio 3.643) or any arrhythmias (P = 0.008, odd ratio 6.563). The MACE-free survival rate showed a significant difference in terms of fQRS (P = 0.003; P = 0.007; and P = 0.027). In univariate analyses, age, QRS duration, corrected QT, positive fQRS, and the number of leads with fQRS were significant predictors of MACEs. Among the above factors, positive fQRS at diagnosis was a strongly significant predictor of adverse outcomes in multivariate analyses (hazards ratio 94.529, P = 0.001). Fragmented QRS complex at diagnosis could be used as a strong predictor for cardiac adverse outcomes in pediatric patients with idiopathic DCM.

Background: It was the aim to investigate the frequency and genetic basis of dilated cardiomyopathy (DCM) among relatives of index patients with unexplained heart failure at a tertiary referral center., Methods: Clinical investigations were performed in 109 DCM index patients and 445 of their relatives. All index patients underwent genetic investigations of 76 disease-associated DCM genes. A family history of DCM occurred in 11% (n=12) while clinical investigations identified familial DCM in a total of 32% (n=35). One-fifth of all relatives (n=95) had DCM of whom 60% (n=57) had symptoms of heart failure at diagnosis, whereas 40% (n=38) were asymptomatic. Symptomatic relatives had a shorter event-free survival than asymptomatic DCM relatives ( P <0.001)., Results: Genetic investigations identified 43 pathogenic (n=27) or likely pathogenic (n=16) variants according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Forty-four percent (n=48/109) of index patients carried a pathogenic/likely pathogenic variant of whom 36% (n=27/74) had sporadic DCM, whereas 60% (21/35) were familial cases. Thirteen of the pathogenic/likely pathogenic variants were also present in ≥7 affected individuals and thereby considered to be of sufficient high confidence for use in predictive genetic testing., Conclusions: A family history of DCM identified only 34% (n=12/35) of hereditary DCM, whereas systematic clinical screening identified the remaining 66% (n=23) of DCM families. This emphasized the importance of clinical investigations to identify familial DCM. The high number of pathogenic/likely pathogenic variants identified in familial DCM provides a firm basis for offering genetic investigations in affected families. This should also be considered in sporadic cases since adequate family evaluation may not always be possible and the results of the genetic investigations may carry prognostic information with an impact on individual management.

Background: Genetic analysis is a first-tier test in dilated cardiomyopathy (DCM). Electrical phenotypes are common in genetic DCM, but their exact contribution to the clinical course and outcome is unknown. We determined the prevalence of pathogenic gene variants in a large unselected DCM population and determined the role of electrical phenotypes in association with outcome., Methods: This study included 689 patients with DCM from the Maastricht Cardiomyopathy Registry, undergoing genetic evaluation using a 48 cardiomyopathy-associated gene-panel, echocardiography, endomyocardial biopsies, and Holter monitoring. Upon detection of a pathogenic variant in a patient with DCM, familial segregation was performed. Outcome was defined as cardiovascular death, heart transplantation, heart failure hospitalization, and/or occurrence of life-threatening arrhythmias., Results: A (likely) pathogenic gene variant was found in 19% of patients, varying from 36% in familial to 13% in nonfamilial DCM. Family segregation analysis showed familial disease in 46% of patients with DCM who were initially deemed nonfamilial by history. Overall, 18% of patients with a nongenetic risk factor had a pathogenic gene variant. Almost all pathogenic gene variants occurred in just 12 genes previously shown to have robust disease association with DCM. Genetic DCM was independently associated with electrical phenotypes such as atrial fibrillation, nonsustained ventricular tachycardia, and atrioventricular block and inversely correlated with the presence of a left bundle branch block ( P <0.01). After a median follow-up of 4 years, event-free survival was reduced in genetic versus patients with nongenetic DCM ( P =0.01). This effect on outcome was mediated by the associated electrical phenotypes of genetic DCM ( P <0.001)., Conclusions: One in 5 patients with an established nongenetic risk factor or a nonfamilial disease still carries a pathogenic gene variant. Genetic DCM is characterized by a profile of electrical phenotypes (atrial fibrillation, nonsustained ventricular tachycardia, and atrioventricular block), which carries increased risk for adverse outcomes. Based on these findings, we envisage a broader role for genetic testing in DCM.

Background: Left-ventricular systolic dyssynchrony (LVSD) has been an important prognostic factor in the patients with dilated cardiomyopathy (DCM). However, the association between the LV diastolic dyssynchrony (LVDD) and clinical outcome is not well established. This study aims to evaluate the prognostic values of both systolic and diastolic dyssynchrony in patients with DCM., Methods: Fifty-two patients with DCM were enrolled and divided into two groups according to cardiac deaths from the follow-up data. The phase-analysis technique was applied on resting gated short-axis SPECT MPI images to measure LV systolic and diastolic dyssynchrony, including phase standard deviation (PSD), phase histogram bandwidth (PBW), and phase entropy (PE). Variables with P < 0.10 in the univariate analysis were included in the multivariate cox analysis., Results: During the follow-up period (2.9 ± 1.7 years), 18 (34.6%) cardiac deaths were observed. Compared with survivors, patients with cardiac death had lower LVEF (P = 0.011), and more severe LV systolic and diastolic dyssynchrony. The univariate cox regression analysis showed that hypertension, NT-proBNP, LVEF, systolic PSD, systolic PE, and diastolic PBW were statistically significantly associated with cardiac death. The multivariate cox regression analysis showed that systolic PE and diastolic PE were independent predictive factors for cardiac death. Furthermore, the receiver operating characteristic (ROC) analysis, when applied into the combination of systolic PE and diastolic PE for predicting cardiac death, had an area under curve (AUC) of 0.766, a sensitivity of 0.765, and a specificity of 0.722., Conclusions: Both the LVSD and LVDD parameters from SPECT MPI have important prognostic values for DCM patients. Both systolic PE and diastolic PE are independent prognostic factors for cardiac death.

Atrial fibrillation (AF) in congestive heart failure (CHF) is associated with a high risk of mortality and shorter survival times in human and veterinary medicine. A retrospective review of medical records was performed to evaluate the impact of AF on survival times in Doberman Pinschers with dilated cardiomyopathy (DCM). Time of first onset of CHF and its role as a prognostic factor were also determined, as were predictors of AF development. Forty-eight client-owned purebred Doberman Pinschers with DCM and CHF were included; 23 dogs presented with AF and 25 dogs did not develop AF until immediately before cardiac-related death. Dogs with AF survived for significantly shorter times than those without AF (P = 0.043). For dogs with AF, mean and median survival times were 88.2 days and 22 days, respectively (range, 42.1-134.4 days); mean and median survival times for dogs without AF were 150.7 days and 98 days, respectively (range, 98.5-203 days). AF increased the risk of cardiac-related death (hazard ratio [HR], 2.371; 95% confidence intervals [CI], 1.14-4.95; P = 0.021). Biventricular and right atrial dilation was only present in dogs with AF and right atrial enlargement was the only significant predictor of AF after multivariate analysis (P < 0.001). Dogs with AF had significantly higher mean heart rates than dogs without AF (201 beats per min [bpm] vs. 132 bpm; P < 0.001). In conclusion, AF in Doberman Pinschers with DCM and CHF increased the risk of cardiac-related death and reduced survival time., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Elevated plasma levels of asymmetric dimethylarginine (ADMA), an inhibitor of NO synthase, are associated with adverse outcome. There is no data available, whether ADMA levels are associated with arrhythmic death (AD) in patients with ischemic cardiomyopathy (ICM) or non-ischemic, dilated cardiomyopathy (DCM)., Methods and Results: A total of 110 ICM, 52 DCM and 30 control patients were included. Primary outcome parameter of this prospective study was arrhythmic death (AD) or resuscitated cardiac arrest (RCA). Plasma levels of ADMA were significantly higher in ICM (p < 0.001) and in DCM (p < 0.001) patients compared to controls. During a median follow-up of 7.0 years, 62 (32.3%) patients died. AD occurred in 26 patients and RCA was observed in 22 patients. Plasma levels of ADMA were not associated with a significantly increased risk of AD or RCA in ICM (hazard ratio (HR) = 1.37, p = 0.109) or in DCM (HR = 1.06, p = 0.848) patients. No significant association was found with overall mortality in ICM (HR = 1.39, p = 0.079) or DCM (HR = 1.10, p = 0.666) patients. Stratified Kaplan-Meier curves for ADMA levels in the upper tertile (>0.715 µmol/l) or the two lower tertiles (≤0.715 µmol/l) did not show a higher risk for AD or RCA (p = 0.221) or overall mortality (p = 0.548). In patients with left ventricular ejection fraction ≤ 35%, ADMA was not associated with AD or RCA (HR = 1.35, p = 0.084) or with overall mortality (HR = 1.24, p = 0.162)., Conclusions: Plasma levels of ADMA were elevated in patients with ICM or DCM as compared to controls, but were not significantly predictive for overall mortality or the risk for arrhythmic death., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricular dysfunction (RVD) in the setting of left ventricular (LV) myocardial damage is a major cause of morbidity and mortality, and the pulmonary artery pulsatility index (PAPi) is a novel hemodynamic index shown to predict RVD in advanced heart failure. However, it is unknown whether PAPi can predict the long-term prognosis of dilated cardiomyopathy (DCM) even in the mild to moderate phase. This study aimed to assess the ability of PAPi to stratify DCM patients without severe symptoms., Methods and results: Between April 2000 and March 2018, a total of 162 DCM patients with stable symptoms were evaluated, including PAPi, and followed up for a median of 4.91 years. The mean age was 50.9±12.6 years and the mean LV ejection fraction (EF) was 30.5±8.3%. When divided into 2 groups based on median value of PAPi (low, L-PAPi [<3.06] and high, H-PAPi [≥3.06]), even though there were no differences in B-type natriuretic peptide or pulmonary vascular resistance, the probability of cardiac event survival was significantly higher in the L-PAP than in the H-PAP group by Kaplan-Meier analysis (P=0.018). Furthermore, Cox's proportional hazard regression analysis revealed that PAPi was an independent predictor of cardiac events (hazard ratio: 0.782, P=0.010)., Conclusions: Even in patients identified with DCM in the mild to moderate phase, PAPi may help stratify DCM and predict cardiac events.

Background In adults with heart failure, elevated heart rate is associated with lower survival. We determined whether an elevated heart rate was associated with an increased risk of death or heart transplant in children with dilated cardiomyopathy. Methods and Results The study is an analysis of the Pediatric Cardiomyopathy Registry and includes baseline data, annual follow-up, and censoring events (transplant or death) in 557 children (51% male, median age 1.8 years) with dilated cardiomyopathy diagnosed between 1994 and 2011. An elevated heart rate was defined as 2 or more SDs above the mean heart rate of children, adjusted for age. The primary outcomes were heart transplant and death. Heart rate was elevated in 192 children (34%), who were older (median age, 2.3 versus 0.9 years; P <0.001), more likely to have heart failure symptoms (83% versus 67%; P <0.001), had worse ventricular function (median fractional shortening z score, -9.7 versus -9.1; P =0.02), and were more often receiving anticongestive therapies (96% versus 86%; P <0.001) than were children with a normal heart rate. Controlling for age, ventricular function, and cardiac medications, an elevated heart rate was independently associated with death (adjusted hazard ratio [HR] 2.6; P <0.001) and with death or transplant (adjusted HR 1.5; P =0.01). Conclusions In children with dilated cardiomyopathy, elevated heart rate was associated with an increased risk of death and cardiac transplant. Further study is warranted into the association of elevated heart rate and disease severity in children with dilated cardiomyopathy and as a potential target of therapy.

Heart failure (HF) is an increasing global health crisis, affecting 40 million people and causing 50% mortality within 5 years of diagnosis. A fuller understanding of the genetic and environmental factors underlying HF, and novel therapeutic approaches to address it, are urgently warranted. Here, we discovered that cardiac-specific germline deletion in mice of potassium channel β subunit-encoding Kcne2 (Kcne2 CS-/- ) causes dilated cardiomyopathy and terminal HF (median longevity, 28 weeks). Mice with global Kcne2 deletion (Kcne2 Glo-/- ) exhibit multiple HF risk factors, yet, paradoxically survived over twice as long as Kcne2 CS-/- mice. Global Kcne2 deletion, which inhibits gastric acid secretion, reduced the relative abundance of species within Bacteroidales, a bacterial order that positively correlates with increased lifetime risk of human cardiovascular disease. Strikingly, the proton-pump inhibitor omeprazole similarly altered the microbiome and delayed terminal HF in Kcne2 CS-/- mice, increasing survival 10-fold at 44 weeks. Thus, genetic or pharmacologic induction of hypochlorhydria and decreased gut Bacteroidales species are associated with lifespan extension in a novel HF model., (© 2020 Federation of American Societies for Experimental Biology.)

Background: The clinical characteristics and prognostic outcomes of dilated cardiomyopathy (DCM) with a familial history (FHx) via pedigree analysis are unclear., Methods and results: We conducted a prospective observational study of 514 consecutive Japanese patients with DCM. FHx was defined as the presence of DCM in ≥1 family member within 2-degrees relative based on pedigree analysis. The primary endpoint was a composite of major cardiac events (sudden cardiac death and pump failure death). The prevalence of FHx was 7.4% (n=38). During a median follow-up of 3.6 years, 77 (15%) patients experienced a major cardiac event. Multivariable Cox regression analysis identified FHx as independently associated with major cardiac events (hazard ratio [HR] 4.32; 95% confidence interval [CI], 2.04-9.19; P<0.001) compared with conventional risk factors such as age, QRS duration, and left ventricular volume. In the propensity score-matched cohort (n=38 each), the FHx group had a significantly higher incidence of major cardiac events (HR, 4.48; 95% CI, 1.25-16.13; P=0.022). In addition, the FHx group had a higher prevalence of a diffuse late gadolinium enhancement (LGE) pattern than the no-FHx group (32% vs. 17%, P=0.022)., Conclusions: DCM patients with FHx had a worse prognosis, which was associated with a higher prevalence of a diffuse LGE pattern, than patients without FHx.

Background: We aimed to develop a risk score (LGE Based Prediction of SCD Risk in Nonischemic Dilated Cardiomyopathy [ESTIMATED]) based on late gadolinium enhancement (LGE) cardiac magnetic resonance to predict sudden cardiac death (SCD) in patients with nonischemic dilated cardiomyopathy (NIDCM) and left ventricular ejection fraction ≤ 35%., Methods: We recruited 395 consecutive middle-aged patients with NIDCM and performed 3-year follow-up for SCD events. The score was developed and verified in 295 primary prevention patients, and the predictive value was confirmed by comparing the SCD events between the high-risk patients stratified by the score and 100 secondary prevention patients., Results: The ESTIMATED score (constructed by the LGE extent > 14%, syncope, atrial flutter/fibrillation, nonsustained ventricular tachycardia, advanced atrioventricular block, and age ≤ 20 or > 50 years) showed good calibrations for SCD prediction in the derivation (C-statistic: 0.80, 95% confidence interval: 0.74-0.86) and validation set (C-statistic: 0.80, 95% confidence interval: 0.71-0.87). By the score, 20.3% of primary prevention patients were categorized as high risk (≥ 3 points), 28.1% as intermediate risk (2 points), and 51.6% as low risk (0-1 points) for 3-year SCD events (45.9% vs 20.1% vs 5.1%, P < 0.0001). The 3-year SCD events were also well in agreement with the score stratification in patients without implantable cardioverter-defibrillator. High-risk primary prevention patients selected by the score in the derivation and validation sets had 3-year SCD events comparable with that in secondary prevention patients (47.6% vs 40.6% vs 38.7%, P = 0.81)., Conclusions: Our study derived and validated an LGE-based (ESTIMATED) risk score providing refined SCD prediction. The score may help to identify candidates for primary prevention implantable cardioverter-defibrillator in patients with NIDCM., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) longitudinal dysfunction has been identified in type 2 diabetes mellitus (T2DM) patients with preserved LV ejection fraction (LVEF). However, the impact of T2DM on LV longitudinal function or the association of LV longitudinal function with outcome for dilated cardiomyopathy (DCM) remains unclear., Methods: We retrospectively studied 206 patients with non-ischemic DCM, mean age of 59 ± 17 years and LVEF of 31 ± 8% (all < 45%). All patients underwent a standard echocardiographic examination, and LV longitudinal function was assessed in terms of global longitudinal strain (GLS). Long-term outcomes were assessed, with a median follow-up period of 6.2 years, as primary endpoints of death from or hospitalization for deteriorating heart failure., Results: GLS of DCM patients with T2DM (n = 55) was significantly lower than that in DCM patients without T2DM (n = 151) in spite of similar conventional LV function (7.0 ± 2.0% vs. 7.8 ± 2.2%, p = 0.03). Kaplan-Meier curves indicated that long-term outcomes for DCM patients without T2DM were better than for those with T2DM (log-rank p = 0.001). Subdividing the two groups into four with by using the median value of GLS (7.9%) showed long-term outcome was worst for DCM patients with T2DM and low GLS. Cox proportional hazards analyses demonstrated an independent association of T2DM, GLS and left atrial volume index with long-term outcome. Moreover, multiple regression analysis for the association of GLS showed that T2DM was the independent determinant parameter for GLS as well as for LVEF and left atrial volume index., Conclusion: Management of DCM patients with T2DM may be improved by using GLS guidance.

Background Genetic testing in pediatric primary dilated cardiomyopathy (DCM) patients has identified numerous disease-causing variants, but few studies have evaluated genetic testing outcomes in this population in the context of patient and familial clinical data or assessed the clinical implications of temporal changes in genetic testing results. Methods and Results We performed a retrospective analysis of all patients with primary DCM who presented to our institution between 2008 and 2018. Variants identified by genetic testing were reevaluated for pathogenicity on the basis of current guidelines for variant classification. A total of 73 patients with primary DCM presented to our institution and 63 (86%) were probands that underwent cardiomyopathy-specific gene testing. A disease-causing variant was identified in 19 of 63 (30%) of cases, with at least 9/19 (47%) variants occurring de novo. Positive family history was not associated with identification of a causal variant. Reclassification of variants resulted in the downgrading of a large proportion of variants of uncertain significance and did not identify any new disease-causing variants. Conclusions Clinical genetic testing identifies a causal variant in one third of pediatric patients with primary DCM. Variant reevaluation significantly decreased the number of variants of uncertain significance, but a large burden of variants of uncertain significance remain. These results highlight the need for periodic reanalysis of genetic testing results, additional investigation of genotype-phenotype correlations in DCM through large, multicenter genetic studies, and development of improved tools for functional characterization of variants of uncertain significance.

Ventricular assist devices (VADs) are life-saving options for children with heart failure unresponsive to medical therapy as a bridge to transplantation or cardiac recovery. We present a retrospective review of 13 consecutive children who underwent implantation of VAD between 2001 and 2018 in our center. The median age was 12 years (1-17 years), weight was 45 kg (10-82 kg). Etiologies of heart failure were dilated cardiomyopathy (CMP) (n = 8), myocarditis (n = 2), ischemic CMP (n = 1), restrictive CMP (n = 1) and congenital heart disease (n = 1). Pre-implantation ECMO was used in 5, mechanical ventilation in 4, renal replacement therapy in 2 and IABP in 1. Devices used were: Berlin Heart EXCOR left VAD (LVAD), biventricular VAD (BIVAD) (n = 5, 2), CentriMag LVAD, BIVAD (n = 1, 2), HeartWare (n = 2), HeartMate II (n = 1). Median duration of support was 45 days (3-823 days). Overall survival was 85%. Four patients were successfully bridged to transplantation, 2 died while on a device, 4 remain on support and 3 were weaned from VAD. Late death occurred in 2 transplanted patients. Complications included bleeding requiring reoperation in 1, neurologic events in 3, driveline infections and pericardial effusion in 2 each. In one patient, CentriMag BIVAD provided support for 235 days, which is longest reported duration on such a VAD in the Asia Pacific region. Survival for pediatric patients of all ages is excellent using VADs. Given the severity of illness in these children morbidity and mortality is acceptable. VADs could potentially be used as a long-term bridge to transplantation in view of the donor shortage in the pediatric population.

Background: Chemerin is a newly discovered adipokine, which has been reported to be associated with the presence of dilated cardiomyopathy (DCM). The present study aims to evaluate the prognostic value of serum chemerin in patients with DCM., Methods: A total of 214 patients with DCM was recruited and divided into 4 groups, according to quartiles of chemerin levels. Kaplan-Meier analysis was conducted to compare the survival rates among patients with different levels of chemerin, using the log-rank test. Multivariate Cox regression analysis was performed to assess the association of serum chemerin levels and occurrence of major adverse cardiac events (MACEs), including cardiac mortality, stroke and myocardial infarction., Results: The Kaplan-Meier survival analysis indicated that patients with higher concentration of chemerin had shorter event-free survivals for MACEs (P < .01). Cox regression analysis showed that chemerin was a significant predictor of MACEs (Quartile 3 versus Quartile 1: HR=1.79, 95% CI: 1.31-2.79; Quartile 4 versus Quartile 1: HR=2.87, 95% CI: 1.79-4.25) and all-cause death (Quartile 3 versus Quartile 1: HR=1.56, 95% CI: 1.20-2.42; Quartile 4 versus Quartile 1: HR=2.28, 95% CI: 1.52-3.96) after adjusting for potential risk factors., Conclusion: Serum chemerin should be a potential prognostic indicator in patients with DCM.

The mortality causes of patients followed up due to dilated cardiomyopathy (DCM) include complications related to heart failure, ventricular arrhythmia, and transplantation. This study aims to evaluate the electrocardiographic findings of patients diagnosed with dilated cardiomyopathy and determine its relationship with mortality. The electrocardiographic, clinical, and laboratory findings of patients diagnosed with dilated cardiomyopathy between January 1, 2012, and September 1, 2018, in our university's pediatric cardiology department were retrospectively evaluated. The electrocardiographic findings of surviving and exitus dilated cardiomyopathy patients were compared and their effect on mortality was investigated. Twelve of the total 85 patients diagnosed with dilated cardiomyopathy were deceased. According to the electrocardiographic findings of surviving and exitus patients, there was a statistically significant difference in terms of P maximum (Pmax), P dispersion (Pdis), QT dispersion (QTdis), QTc maximum (QTcmax), QTc dispersion (QTcdis), Tp-e maximum (Tp-emax), Tp-e dispersion (Tp-edis), and QRS time. Hypertrophy and ischemia findings of electrocardiography were also statistically significant. There was a statistically significant difference between the two groups according to the echocardiographic findings of left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVSF), left ventricular end-diastolic diameter (LVEDd), and left ventricular end-systolic diameter (LVESd) measurements. It is well known that children diagnosed with dilated cardiomyopathy are at greater risk of arrhythmia compared with normal children. Although previous studies have determined the relationship between mortality and a limited number of electrocardiographic findings, especially in adults, the relationship between electrocardiography findings of children diagnosed with DCM and mortality has not been investigated before in such detail, as in our study.Conclusion: In this study, the significant difference between the electrocardiographic data of deceased and surviving dilated cardiomyopathy patients suggests that electrocardiographic data should be evaluated in detail in order to determine the low and high risk of mortality in patients with dilated cardiomyopathy.What is Known:• Previous studies on the relationship between limited electrocardiography data of adult patients diagnosed with DCM and mortality have been determinedWhat is New:• ECG data has not been investigated in such detail in child DCM patients, as in our study.

Background: Dilated cardiomyopathy (DCM) in children is an important cause of severe heart failure and carries a poor prognosis. Adults with heart failure are at increased risk of anxiety and depression and such symptoms predict adverse clinical outcomes such as mortality. In children with DCM, studies examining these associations are scarce., Aims: We studied whether in children with DCM: (1) the level of emotional and behavioral problems was increased as compared to normative data, and (2) depressive and anxiety problems were associated with the combined risk of death or cardiac transplantation., Methods: To assess emotional and behavioral problems in children with DCM, parents of 68 children, aged 1.5-18 years (6.9±5.7 years), completed the Child Behavior Checklist., Results: Compared to normative data, more young children (1.5-5 years) with DCM had somatic complaints (24.3% vs. 8.0%; p < .001), but fewer had externalizing problems (5.4% vs. 17.0%; p = .049). Overall internalizing problems did not reach significance. Compared to normative data, more older children (6-18 years) showed internalizing problems (38.7% vs. 17.0%; p = .001), including depressive (29.0% vs. 8.0%; p < .001) and anxiety problems (19.4% vs. 8.0%; p = .023), and somatic complaints (29.0% vs. 8.0%; p < .001). Anxiety and depressive problems, corrected for heart failure severity, did not predict the risk of death or cardiac transplantation., Conclusion: Children of 6 years and older showed more depressive and anxiety problems than the normative population. Moreover, in both age groups, somatic problems were common. No association with outcome could be demonstrated.

Dilated cardiomyopathy (DCM) is a common condition, which carries significant mortality from sudden cardiac death and pump failure. Left ventricular ejection fraction has conventionally been used as a risk marker for sudden cardiac death, but has performed poorly in trials. There have been significant advances in the areas of cardiac magnetic resonance imaging and genetics, which are able to provide useful rick prediction in DCM. Biomarkers and cardiopulmonary exercise testing are well validated in the prediction of risk in heart failure; however, they have been tested less specifically in the DCM setting. This review will discuss these methods with a view toward multiparametric risk assessment in DCM with the hope of creating parametric risk models to predict sudden cardiac death and pump failure in the DCM population., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Background and Aims: The prognostic nutritional index (PNI) had been associated with adverse outcomes in numerous clinical conditions. However, its influence on idiopathic dilated cardiomyopathy (DCM) was not determined. This aim of this study was to determine the predictive ability of PNI in patients with idiopathic DCM., Methods and Results: A total of 1021 consecutive patients with idiopathic DCM were retrospectively included and divided into three groups based on admission PNI tertiles: <41.7 (n = 339), 41.7-47.3 (n = 342), >47.3 (n = 340). The association of PNI with in-hospital major adverse clinical events (MACEs) and death during follow-up was evaluated. In-hospital mortality (2.9% vs. 1.5% vs. 0.0%, respectively; p = 0.006) and MACEs (13.6% vs. 6.7% vs. 3.5%, respectively; p < 0.001) decreased from the lowest to the highest PNI tertile. The optimal cut-off value of PNI to predict in-hospital MACEs was 44.0 (area under the curve: 0.689; 95% confidence interval [CI]: 0.626-0.753; p < 0.001). Multivariate analysis showed that a PNI≤44.0 was an independent risk factor of in-hospital MACEs (odd ratio: 2.86; 95% CI: 1.64-4.98; p < 0.001) and all-cause mortality at a median follow-up of 27 months (hazard ratio: 1.67; 95% CI: 1.11-2.49; p = 0.013). In addition, patients with a PNI≤44.0 had a lower cumulative survival rate during follow-up (log-rank: 35.62; p < 0.001)., Conclusion: The PNI was an independent risk factor for in-hospital MACEs and all-cause mortality at a median follow-up of 27 months in patients with idiopathic DCM; hence, it may be considered a tool for risk assessment., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

SGLT-2 inhibitors and most GLP-1 receptor agonists demonstrated cardiovascular superiority and reduction of cardiovascular and overall mortality. These results stand as a turning point in the management of diabetes, shifting the focus from controlling glucose levels to mastering the extra-glycemic effects of these new drugs. This narrative review will discuss recent CVOT with focus on SGLT-2 inhibitors and GLP-1 receptor agonists to distinguish relevant patients' characteristics as potential predictors for therapeutic efficacy. It will also examine their efficacy and safety, the differences in their cardiovascular and renal benefits, aiming to convey clinical suggestions for everyday practice., Competing Interests: Declaration of competing interest F.G.: Research support: Eli Lilly, LifeScan, Takeda Medical Research Foundation. Consultant and author for AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Merck Sharp and Dohme, NovoNordisk, Roche Diabetes Care, Sanofi. M.L.: Research support: Boehringer Ingelheim, MSD, Novo Nordisk, Consultant and author for Boehringer Ingelheim, MSD, Novo Nordisk, Amgen, Sanofi, Astra Zeneca, Bayer and Lilly., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The imaging features of dilated cardiomyopathy (DCM) overlap with physiological exercise-induced cardiac remodeling in active and otherwise healthy individuals. Distinguishing the two conditions is challenging. This study examined the diagnostic and prognostic roles of exercise stress imaging in asymptomatic patients with suspected DCM., Methods: Exercise stress cardiovascular magnetic resonance (CMR) was performed in 60 asymptomatic patients with suspected DCM (dilated left ventricle and/or impaired systolic function on CMR), who also underwent DNA sequencing for DCM-causing genetic variants. Confirmed DCM was defined as genotype- and phenotype-positive (G+P+). Another 100 healthy subjects were recruited to establish normal exercise capacities (peak exercise cardiac index; Peak CI ). The primary outcome was a composite of all-cause mortality, cardiac decompensation and ventricular arrhythmic events., Results: No patients with confirmed G+P+ DCM had Peak CI exceeding the 35th percentile specific for age and sex. Applying this threshold in G-P+ patients, those with Peak CI below 35th percentile had characteristics similar to confirmed DCM while patients with higher Peak CI were younger, more active and higher longitudinal strain. Adverse cardiovascular events occurred only in patients with low exercise capacity (P = 0.004)., Conclusions: In individuals with suspected DCM, exercise stress CMR demonstrates diagnostic and prognostic potential in distinguishing between pathological DCM and physiological exercise-induced cardiac remodeling.