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Background: Patients with dilated cardiomyopathy (DCM) who are undergoing catheter ablation of ventricular arrhythmias (VAs) are at risk of rapidly progressive heart failure (HF). Endocardial voltages decrease with loss of viable myocardium. Global left ventricular (LV) voltage as a surrogate for the amount of remaining viable myocardium may predict prognosis., Objectives: This study evaluated whether the newly proposed parameter volume-weighted (vw) unipolar voltage (UV) can predict HF-related adverse outcomes (HFOs), including death, heart transplantation, or ventricular assist device implantation, in DCM., Methods: In consecutive patients with DCM referred for VA ablation, vwUV was calculated by mathematically integrating UV over the left ventricle, divided by the endocardial LV surface area and wall thickness. Patients were followed for HFOs., Results: A total of 103 patients (57 ± 14 years of age; left ventricular ejection fraction [LVEF], 39% ± 13%) were included. Median vwUV was 9.75 (IQR: 7.27-12.29). During a median follow-up of 24 months (IQR: 8-47 months), 25 patients (24%) died, and 16 had HFOs 7 months (IQR: 1-18 months) after ablation. Patients with HFOs had significantly lower LVEF (29% ± 10% vs 41% ± 12%), vw bipolar voltage (BV) (3.00 [IQR: 2.47-3.53] vs 5.00 [IQR: 4.12-5.73]), and vwUV (5.94 [IQR: 5.28-6.55] vs 10.37 [IQR: 8.82-12.81]; all P < 0.001), than patients without HFOs. In Cox regression analysis and goodness-of-fit tests, vwUV was the strongest and independent predictor for HFOs (HR: 3.68; CI: 2.09-6.45; likelihood ratio chi-square, 33.05; P < 0.001)., Conclusions: The novel parameter vwUV, as a surrogate for the amount of viable myocardium, identifies patients with DCM with VA who are at high risk for HF progression and mortality., Competing Interests: Funding Support and Author Disclosures The Department of Cardiology Leiden receives unrestricted research and fellowship grants from Edward Lifesciences, Boston Scientific, Medtronic, and Biotronik. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective Spontaneous mechanical alternans (MA), or pulsus alternans, has been observed in heart failure patients with hypertension or tachycardia for 150 years and is considered a sign of a poor prognosis. However, in some dilated cardiomyopathy (DCM) patients with MA, optimal medical therapy (OMT) brings left ventricular reverse remodeling (LVRR), a preferable prognostic indicator. This study examined the probability of LVRR in DCM patients with spontaneous MA and whether or not LVRR can be predicted by the baseline blood pressure or heart rate. Methods We conducted a single-center, retrospective observational study of newly diagnosed DCM patients from January 2017 to December 2020. Results Thirty-three newly diagnosed DCM patients were retrospectively examined. Spontaneous MA was observed during diagnostic cardiac catheterization in at least 1 of the pressure waveforms of the aorta, left ventricle, pulmonary artery, or right ventricle in 10 patients (30%) (MA-group). LVRR after OMT was achieved roughly equally in the MA group (6 of 10, 60%) and the non-MA group (12 of 23, 52%). In the MA group, those who achieved LVRR had a significantly higher baseline systolic aortic pressure (more than 120 mmHg in all 6 patients) than those who did not, although the baseline heart rate did not show a significant correlation with LVRR. In contrast, in the non-MA group, LVRR was unrelated to the baseline aortic pressure or heart rate. Conclusion The probability of LVRR in newly-diagnosed DCM patients with spontaneous MA was similar to that in those without spontaneous MA. Spontaneous MA may not necessarily be a sign of a poor prognosis if observed in patients with a preserved blood pressure.

Contraction of the human sarcomere is the result of interactions between myosin cross-bridges and actin filaments. Pathogenic variants in genes such as MYH7 , TPM1 , and TNNI3 that encode parts of the cardiac sarcomere cause muscle diseases that affect the heart, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In contrast, pathogenic variants in homologous genes such as MYH2 , TPM2 , and TNNI2 that encode parts of the skeletal muscle sarcomere cause muscle diseases affecting skeletal muscle, such as distal arthrogryposis (DA) syndromes and skeletal myopathies. To date, there have been few reports of genes (e.g., MYH7 ) encoding sarcomeric proteins in which the same pathogenic variant affects skeletal and cardiac muscle. Moreover, none of the known genes underlying DA have been found to contain pathogenic variants that also cause cardiac abnormalities. We report five families with DA because of heterozygous missense variants in the gene actin , alpha , cardiac muscle 1 ( ACTC1 ). ACTC1 encodes a highly conserved actin that binds to myosin in cardiac and skeletal muscle. Pathogenic variants in ACTC1 have been found previously to underlie atrial septal defect, dilated cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction. Our discovery delineates a new DA condition because of variants in ACTC1 and suggests that some functions of ACTC1 are shared in cardiac and skeletal muscle., Competing Interests: M.J.B. and J.X.C. are the Editor-in-Chief and Deputy Editor of HGG Advances, respectively, and were recused from the editorial handling of this manuscript., (© 2023 The Author(s).)

Background: Patients with nonischemic dilated cardiomyopathy (DCM) are susceptible to arrhythmias and implantable cardioverter defibrillator (ICD) in addition to medical treatments may help prevent sudden cardiac death (SCD) and improve survival in this population., Hypothesis: We aim to investigate the impact of ICD insertion on survival and prognosis of patients with nonischemic DCM., Methods: We retrospectively analyzed data from patients with nonischemic DCM treated with medical therapy with or without ICD who referred to our hospital from January 2020 to November 2021. Patients were divided based on the treatment that they had received into two equal groups. Different variables including demographic features, comorbidities, medical treatments, hospitalization rate, function class, and left ventricular ejection fraction before and after treatments were investigated in this study. In addition, variables in survival including overall survival (OS) and SCD were compared between the two groups., Results: A total of 120 patients were investigated in this study. Mean ± SD of age and follow-up time of patients were 64.0 ± 12.7 years old and 61.2 ± 15.9 months, respectively. Ten (16.7%) patients with medical therapy, and seven (11.7%) patients with ICD and medical therapy died during the follow-up period (p = 0.25). However, the two groups had a significant difference regarding SCD (11.7% vs. 1.7%, p = 0.02)., Conclusion: In patients with nonischemic DCM who had undergone ICD insertion in addition to standard medical treatments, SCD was significantly reduced compared with patients receiving just medical treatments. OS had no significant difference between our two studied groups., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Aim: To investigate the pattern of left ventricular (LV) function and myocardial perfusion and their relationship in dilated cardiomyopathy (DCM) patients using layer-specific speckle tracking imaging (STI) and layer-specific myocardial contrast echocardiography (MCE)., Material and Methods: Thirty DCM patients and 30 controls were recruited and underwent STI and MCE examination. The peak values of longitudinal strain (LS), circumferential strain (CS) of each layer of LV were recorded and compared between groups. Additionally, cross-sectional area of a microvessel (A) and average myocardial microvascular lesion (β) of each layer were measured, myocardial blood flow (MBF) was estimated using A × β, above parameters were compared between two groups., Results: The LS of endo- (LS endo ), mid- (LS mid ) and epicardium (LS epi ), as well as CS of endo- (RS endo ), mid- (RS mid ), (LS epi ) epicardium and LS endo/epi, CS endo/epi were significantly decreased in DCM patients. More importantly, DCM patients demonstrated decreased A, β and A × β in all three myocardium layers and A endo/epi, β endo/epi, A × β endo/epi compared to the controls. The time to peak and the cardiac cycle required to reach the peak were prolonged in DCM patients (p < 0.05). Longitudinal strain parameters of each layer had a negative relationship with perfusion parameter A and this relationship was strongest between LSendo and Aendo (r = 0.690, p < 0.01)., Conclusions: The cardiac strain and, more importantly, coronary microcirculation perfusion was impaired in each layer in DCM patients. The longitudinal function of the LV myocardium was closely related to changes in myocardial microcirculation perfusion., (© 2022 Wiley Periodicals LLC.)

Background: Advanced heart failure studies demonstrate that ischemic factors increase in prevalence with age and are more prominent in men. Ejection fraction (EF) cannot be preserved in these patients, and ischemic cardiomyopathy develops. Non-ischemic factors are more prominent in female heart failure patients, where the EF is preserved. Although an age-associated increase in the rate of heart failure is acknowledged in both sexes, etiologic classifications by sex-based age groups are still lacking. This study examined the etiology of heart failure according to age and sex in ventricular assist device patients., Methods: The patient population included 457 end-stage heart failure patients who received a continuous flow-left ventricular assist device at Ege University Hospital between 2010 and 2017. Age, sex, and cardiomyopathy etiology data were obtained from the hospital database. The Mann-Whitney U test was applied to test the statistical significance among subgroups (95% CI, P < .05 for statistical significance)., Results: The prevalence of ischemic cardiomyopathy was significantly lower in male patients aged 18 to 39 years compared to older patients. Conversely, no difference was seen among female patients. The prevalence of dilated cardiomyopathy was higher in male patients who were 18 to 39 years of age compared to older patients, but no difference was present among the female patients., Conclusions: Age and heart failure etiology were demonstrated to be interrelated in men but not in women. The fact that etiologic factors of advanced heart failure in women have a wider range than in men makes the current classification systems insufficient for use in female populations., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to assess the safety and efficacy of long-term milrinone therapy in children with acute decompensated heart failure due to dilated cardiomyopathy (DCM)., Methods: A single-centre retrospective study of all children ≤18 years with acute decompensated heart failure and DCM who received continuous long-term (≥7 consecutive days) intravenous milrinone between January 2008 and January 2022., Results: The 47 patients had a median age of 3.3 months [interquartile range (IQR) 1.0-18.1], weight of 5.7 kg [IQR 4.3-10.1] and fractional shortening of 11.9% [±4.7]. Idiopathic DCM (n = 19) and myocarditis (n = 18) were the most common diagnoses. The median milrinone infusion duration was 27 days [IQR 10-50, range 7-290]. No adverse events necessitated milrinone termination. Nine patients required mechanical circulatory support. Median follow-up was 4.2 years [IQR 2.7-8.6]. On initial admission, four patients died, six were transplanted and 79% [37/47] were discharged home. The 18 readmissions resulted in five more deaths and four transplantations. Cardiac function recovered in 60% [28/47], as measured by normalised fractional shortening., Conclusion: Long-term intravenous milrinone is safe and effective in paediatric acute decompensated DCM. Combined with conventional heart failure therapies, it can act as a bridge to recovery and thereby potentially reduce the need for mechanical support or heart transplantation., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: In patients with ischemic mitral regurgitation (MR) undergoing restrictive mitral annuloplasty (RMA), the ratio of left ventricular (LV) end-systolic dimension (LVESD) to mitral valve (MV) ring size (ie, LV-MV ring mismatch) is associated with postoperative recurrent MR. However, the impact of LV-MV ring mismatch on postoperative recurrent MR, LV function recovery, and long-term survival in patients with nonischemic dilated cardiomyopathy (DCM) remains unknown., Methods: Sixty-six patients with nonischemic DCM (mean LVESD, 62 mm) underwent RMA (mean ring size, 26 mm) between 2003 and 2014. Recurrent MR was defined as MR grade ≥2+ at a 6-month echocardiographic evaluation., Results: At the 6-month follow-up, 23 patients (35%) had developed recurrent MR. In univariable logistic regression analysis, larger LVESD (P = .012) and LVESD/ring size ratio (P = .008) were associated with recurrent MR. In multivariable models adjusted for age, sex, baseline LV ejection fraction, and severe MR, only LVESD/ring size ratio (odds ratio, 4.65; 95% confidence interval, 1.04-25.0; P = .048) remained significantly associated with MR recurrence. Receiver operating characteristic curve analysis demonstrated an optimal cutoff value for the LVESD/ring size ratio of 2.42. Patients with an LVESD/ring size ratio >2.42 (n = 30; mismatch) had a lower 5-year cumulative survival rate compared with those with an LVESD/ring size ratio ≤2.42 (n = 36; nonmismatch) (52% vs 71%; P = .045). Postoperatively, LV dimensions were significantly reduced in both groups; however, improvements in LVEF were only modest in the mismatched group (P = .091)., Conclusions: LV-MV ring size mismatch was associated with an increased risk of recurrent MR in our series. This finding may aid the formulation of surgical strategies for patients with nonischemic DCM., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Paediatric Bow Hunter's syndrome (BHS), or rotational vertebral artery syndrome, is a rare cause of posterior circulation insufficiency in children. It results from mechanical obstruction of the vertebral artery by the transverse process of cervical vertebrae resulting in vertebrobasilar insufficiency during the neck rotation to the sides. Paediatric dilated cardiomyopathy (DCM) is a rare myocardial disease that presents with ventricular dilatation and cardiac dysfunction. This case report describes the successful anaesthetic management of an boy with BHS due to atlantoaxial dislocation and DCM. The child was anaesthetised by keeping the following anaesthetic goals in mind such as maintenance of the heart rate, rhythm, preload, afterload and contractility close to the baseline for both DCM and BHS. Haemodynamic management with optimal fluids, inotrope and a vasopressor and titrating its volume and doses using multimodal haemodynamic monitoring while keeping both cardio and neuroprotective strategies, and the multimodal analgesia techniques helped the child for faster recovery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The present case describes a dilated cardiomyopathy associated with both antidromic and orthodromic atrio-ventricular reentrant tachycardias supported by multiple right accessory pathways. Both right accessory pathways were successfully eliminated by catheter ablation and the patient progressively recovered during the follow up. The following etiologies might be involved: 1) primitive dilated cardiomyopathy (or post-inflammatory); 2) septal dyssinchrony due to ventricular pre-excitation; 3) tachycardiomyopathy., Competing Interests: Declaration of Competing Interest No conflicts of interest to be declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There are 30%-40% of patients with dilated cardiomyopathy (DCM) having genetic causes, among which Lamin A and C gene (LMNA) mutation is the second most frequent DCM-related mutation, and Lamin A/C may be involved in the pathogenesis of DCM through the regulation of gene transcription or the direct effect of cell structure. Methods: Echocardiography and electrocardiogram were used to diagnose DCM and arrhythmia in a DCM family. Then, linked mutations on LMNA were screened out by high-throughput sequencing and verified by Sanger sequencing in all research individuals. Meanwhile, Human Genome Variation Society (HGVS) and Integrative Genomics Viewer (IGV) were used to analyse the characteristics of the mutated Lamin A/C protein. Finally, mutated-type and wild-type LMNA plasmid was transfected into AC-16 cardiomyocytes with the form of a lentivirus vector, and its effect on nucleus and actin was studied by immunofluorescence detection., Results: In this study, we found a new frame-shifted mutation of LMNA (p.Ser414Alafs*66) linked with another point mutation from a DCM family by using High-throughput sequencing, and this deletion mutation led to a truncation of Lamin A/C. By analysing the clinical characteristics of this DCM family, we found that all DCM patients with arrhythmia were carriers of this co-segregation mutation. In the cytological experiment, we found that the mutated-type transfections showed weaker fluorescent intensities on both actin and cell nucleus., Conclusions: A co-segregation mutation of LMNA (Point mutation chr1 156107548 c.1712 G>A and truncated frame-shifted mutation chr1 156106086 c.1240delA) was found from a DCM family, and this type of mutation could participate in the pathogenesis of DCM by affecting the expression of actin.

Protein mutations alter protein-protein interactions that can lead to a number of illnesses. Mutations in lamin A (LMNA) have been reported to cause laminopathies. However, the proteins associated with the LMNA mutation have mostly remained unexplored. Herein, a new chemical tool for proximal proteomics is reported, developed by a combination of proximity chemical tagging and a bio-orthogonal supramolecular latching based on cucurbit[7]uril (CB[7])-based host-guest interactions. As this host-guest interaction acts as a noncovalent clickable motif that can be unclicked on-demand, this new chemical tool is exploited for reliable detection of the proximal proteins of LMNA and its mutant that causes laminopathic dilated cardiomyopathy (DCM). Most importantly, a comparison study reveals, for the first time, mutant-dependent alteration in LMNA proteomic environments, which allows to identify putative laminopathic DCM-linked proteins including FOXJ3 and CELF2. This study demonstrates the feasibility of this chemical tool for reliable proximal proteomics, and its immense potential as a new research platform for discovering biomarkers associated with protein mutation-linked diseases., (© 2023 Wiley-VCH GmbH.)

Background: Cardiac-resident or -enriched microRNAs (miRNAs) could be released into the bloodstream becoming circulating cardiac miRNAs, which are increasingly recognized as non-invasive and accessible biomarkers of multiple heart diseases. However, dilated cardiomyopathy (DCM)-associated circulating miRNAs (DACMs) and their roles in DCM pathogenesis remain largely unexplored., Methods: Two human cohorts, consisting of healthy individuals and DCM patients, were enrolled for serum miRNA sequencing (10 vs. 10) and quantitative polymerase chain reaction validation (46 vs. 54), respectively. Rigorous screening strategy was enacted to define DACMs and their potentials for diagnosis. DCM mouse model, different sources of cardiomyocytes, adeno-associated virus 9 (AAV9), gene knockout, RNAscope miRNA in situ hybridization, mRFP-GFP-LC3B reporter, echocardiography and transmission electron microscopy were adopted for mechanistic explorations., Results: Serum miRNA sequencing revealed a unique expression pattern for DCM circulating miRNAs. DACMs miR-26a-5p, miR-30c-5p, miR-126-5p and miR-126-3p were found to be depleted in DCM circulation as well as heart tissues. Their expressions in circulation and heart tissues were proven to be correlated significantly, and a combination of these miRNAs was suggested potential values for DCM diagnosis. FOXO3, a predicted common target, was experimentally demonstrated to be co-repressed within cardiomyocytes by these DACMs except miR-26a-5p. Delivery of a combination of miR-30c-5p, miR-126-5p and miR-126-3p into the murine myocardium via AAV9 carrying an expression cassette driven by cTnT promoter, or cardiac-specific knockout of FOXO3 (Myh6-Cre ERT2 , FOXO3 flox +/+ ) dramatically attenuated cardiac apoptosis and autophagy involved in DCM progression. Moreover, competitively disrupting the interplay between DACMs and FOXO3 mRNA by specifically introducing their interacting regions into murine myocardium crippled the cardioprotection of DACMs against DCM., Conclusions: Circulating cardiac miRNA-FOXO3 axis plays a pivotal role in safeguarding against myocardial apoptosis and excessive autophagy in DCM development, which may provide serological cues for DCM non-invasive diagnosis and shed light on DCM pathogenesis and therapeutic targets., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

BACKGROUND. Prior small single-center studies have yielded conflicting results regarding the prognostic significance of myocardial strain parameters derived from feature tracking (FT) on cardiac MRI in patients with dilated cardiomyopathy (DCM). OBJECTIVE. The purpose of this study was to evaluate the prognostic utility of FT parameters on cardiac MRI in patients with ischemic and nonischemic DCM and to determine the optimal strain parameter for outcome prediction. METHODS. This retrospective study included 471 patients (median age, 61 years; 365 men, 106 women) with ischemic ( n = 233) or nonischemic ( n = 238) DCM and left ventricular (LV) ejection fraction (EF) less than 50% who underwent cardiac MRI at any of four centers from January 2011 to December 2019. Cardiac MRI parameters were determined by manual contouring. In addition, software-based FT was used to calculate six myocardial strain parameters (LV and right ventricular [RV] global radial strain, global circumferential strain, and global longitudinal strain [GLS]). Late gadolinium enhancement (LGE) was also evaluated. Patients were assessed for a composite outcome of all-cause mortality and/or heart-failure hospitalization. Cox regression models were used to determine associations between strain parameters and the composite outcome. RESULTS. Mean LV EF was 27.5% and mean LV GLS was -6.9%. The median follow-up period was 1328 days. The composite outcome occurred in 220 patients (125 deaths, 95 heart-failure hospitalizations). All six myocardial strain parameters were significant independent predictors of the composite outcome (hazard ratio [HR] = 0.92-1.16; all p < .05). In multivariable models that included age, corrected LV and RV end-diastolic volume, LV and RV EF, and presence of LGE, the only strain parameter that was a significant independent predictor of the composite outcome was LV GLS (HR = 1.13, p = .006); LV EF and presence of LGE were not independent predictors of the composite outcome in the models ( p > .05). A LV GLS threshold of -6.8% had sensitivity of 62.6% and specificity of 62.6% in predicting the composite outcome rate at 4.0 years. CONCLUSION. LV GLS, derived from FT on cardiac MRI, is a significant independent predictor of adverse outcomes in patients with DCM. CLINICAL IMPACT. This study strengthens the body of evidence supporting the clinical implementation of FT when performing cardiac MRI in patients with DCM.

Background: Little is known about nationwide temporal trends in the clinical characteristics and treatment of dilated cardiomyopathy (DCM) in Japan., Methods and results: We collected data regarding demographics, echocardiography, and treatment of DCM between 2003 to 2013 from Clinical Personal Records, a national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Among the 40,794 DCM patients screened, 27,702 with left ventricular ejection fraction (LVEF) <50% and age ≥18 years were enrolled in this study and divided into 3 groups according to registration year: Group 1, 2003-2005 (10,006 patients); Group 2, 2006-2010 (11,252 patients); and Group 3, 2011-2013 (6,444 patients). Over time, there were decreases in age at registration (mean [±SD] 58.6±13.0 vs. 56.8±13.8 vs. 56.2±13.8 years; P<0.001) and LVEF (33.5±10.0% vs. 31.1±9.9% vs. 29.2± 9.7%; P<0.001), and an increase in patients with New York Heart Association Class III-IV (28.2% vs. 35.2% vs. 41.0%; P<0.001). The use of β-blockers (59.1% vs. 79.3% vs. 87.8%; P<0.001) and mineralocorticoid receptor antagonists (30.6% vs. 35.8% vs. 39.7%; P<0.001) increased over time. In multivariate analysis, male sex, systolic blood pressure, chronic kidney disease, hemoglobin, and registration year were positively associated, whereas age and LVEF were negatively associated, with β-blocker prescription., Conclusions: Although the clinical characteristics of DCM changed, the implementation of optimal medical therapy for DCM increased from 2003 to 2013 in Japan.

Emergency cesarean delivery in patients with heart failure increases maternal and fetal mortality. The present study aimed to identify the relationship between the use of anesthesia for delivery and progressive cardiac deterioration in women with dilated cardiomyopathy (DCM) and to examine its implications on maternal and fetal outcomes. Twenty-nine pregnancies in 25 women with DCM from the National Cerebral and Cardiovascular Center Hospital (Suita, Japan) were included in this retrospective longitudinal study. Fourteen of the patients (48.3%) delivered via cesarean section. Among these, 4 patients (13.8%) experienced heart failure within 42 days of delivery. The indication for cesarean delivery was heart failure in 3 patients and induction failure in 1 patient. The types of anesthesia used for these patients included general (n = 1), combined spinal-epidural (n = 2), and epidural (n = 1). Two of these cesarean deliveries were performed preterm. The left ventricular ejection fraction of patients with heart failure was ≤ 35% before 34 weeks gestation. Among the 25 patients without heart failure, 2 exhibited a left ventricular ejection fraction of ≤ 35% before 34 weeks gestation. Meanwhile, the types of anesthesia used for remaining 10 patients who did not experience heart failure included general (n = 1), combined spinal-epidural (n = 8), and epidural (n = 1). The rate of general anesthesia was 25% in patients who experienced heart failure and 4% in others. There was no incidence of maternal or fetal death. A preterm anesthetic evaluation may be warranted to optimize anesthetic management when the ejection fraction decreases to ≤ 35% before 34 weeks gestation in patients with DCM., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: Limited data exist to describe the prognostic impact of atrial fibrillation (AF) and oral anticoagulation on patients with alcoholic cardiomyopathy (ACM) compared with dilated cardiomyopathy (DCM) and were investigated in this study., Methods: Using Danish nationwide registries, a cohort analysis was conducted to assess the prognostic differences for patients with a first diagnosis of ACM versus DCM with and without AF 1994-2018 (followed until end 2019). Our study also assessed differences in mortality following initiation of anticoagulation in both populations., Results: Totally, 1237 patients with ACM (33% with AF) and 17,211 individuals with DCM (33% with AF) were included. Those with ACM were more often men (89 versus 71%) and younger than patients with DCM (mean age 56 versus 64 years). Cumulative 5-year mortality was greater among patients with ACM, compared with DCM, regardless of AF (ACM with AF 49% [95% CI: 44-54%], ACM without AF 48% [45-53%], DCM with AF 41% [39-42%], DCM without AF 30% [29-31%], P < 0.0001). The prognosis associated with AF was statistically significantly different in people with ACM and DCM (adjusted hazards ratio 0.85 [95% CI: 0.74-0.98] versus 1.04 [1.00-1.09] in ACM and DCM, P < 0.0001). The mortality associated with oral anticoagulation was similar in ACM and DCM (hazards ratio 0.81 [0.61-1.07] versus 0.87 [0.80-0.94], P = 0.49)., Conclusions: Patients with ACM had a worse prognosis when compared with patients with DCM, but this did not appear to be driven by AF. Patients with ACM were observed to have similar associated risk benefits of oral anticoagulation as DCM., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background Studies over the past 15 years have demonstrated that a considerable number of patients with dilated cardiomyopathy (DCM) who died from sudden cardiac death (SCD) had a left ventricular (LV) ejection fraction (LVEF) of 35% or higher. Purpose To identify clinical and cardiac MRI risk factors for adverse events in patients with DCM and LVEF of 35% or higher. Materials and Methods In this retrospective study, consecutive patients with DCM and LVEF of 35% or higher who underwent cardiac MRI between January 2010 and December 2017 were included. The primary end point was a composite of SCD or aborted SCD. The secondary end point was a composite of all-cause mortality, heart transplant, or hospitalization for heart failure. The risk factors for the primary and secondary end points were identified with multivariable Cox analysis. Results A total of 466 patients with DCM and LVEF of 35% or higher (mean age, 44 years ± 14 [SD]; 358 men) were included. During a mean follow-up of 79 months ± 30 (SD) (range, 7-143 months), 40 patients reached the primary end point and 61 reached the secondary end point. In the adjusted analysis, age (hazard ratio [HR], 1.03 per year [95% CI: 1.00, 1.05]; P = .04), family history of SCD (HR, 3.4 [95% CI: 1.3, 8.8]; P = .01), New York Heart Association (NYHA) class III or IV (HR vs NYHA class I or II, 2.1 [95% CI: 1.1, 3.9]; P = .02), and myocardial scar at late gadolinium enhancement (LGE) MRI greater than or equal to 7.1% of the LV mass (HR, 4.4 [95% CI: 2.4, 8.3]; P < .001) were associated with SCD or aborted SCD. For the composite secondary end point, LGE greater than or equal to 7.1% of the LV mass (HR vs LGE <7.1%, 2.0 [95% CI: 1.2, 3.4]; P = .01), left atrial maximum volume index, and reduced global longitudinal strain were independent predictors. Conclusion For patients with dilated cardiomyopathy and left ventricular (LV) ejection fraction of 35% or higher, cardiac MRI-defined myocardial scar greater than or equal to 7.1% of the LV mass was associated with sudden cardiac death (SCD) or aborted SCD. © RSNA, 2022 Online supplemental material is available for this article.

This review summarizes the available information on the epidemiology and prognosis of patients with left bundle branch block (LBBB), morphological alterations of the myocardium both resulting in and ensuing LBBB, cardiac biomechanics in LBBB, and possibilities of its correction.

Aims: To evaluate the baseline characteristics and the prognostic implications associated with late gadolinium enhancement limited to the right ventricular insertion points (IP-LGE) or present at both the right ventricular insertion points and the left ventricle (IP&LV-LGE) in non-ischaemic dilated cardiomyopathy (DCM)., Methods and Results: This is a retrospective observational multicentre cohort study including 1165 consecutive patients with DCM evaluated by cardiac magnetic resonance. The primary endpoint included appropriate defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, or sudden death. The secondary outcome encompassed heart failure hospitalizations, heart transplant, left ventricular assist device implantation, and end-stage heart failure death. IP-LGE was found in 72 patients (6%), who had clinical characteristics closer to LGE- than to LGE+ patients. During follow-up (median 36 months), none of the IP-LGE patients experienced the primary endpoint. The cumulative incidence of the primary endpoint was similar between IP-LGE and LGE- patients (P = 1), while IP-LGE had significantly lower cumulative incidence when compared with LGE+ patients (P < 0.001). When compared with IP-LGE patients, the cumulative incidence of the secondary endpoint was similar in LGE- cases (P = 0.86) but tended to be higher in LGE+ patients (P = 0.06). Both clinical characteristics and outcomes were similar between IP&LV-LGE patients and the rest of LGE+ cases., Conclusions: In a large cohort of DCM patients, IP-LGE was associated with similar outcome when compared with LGE- patients and with significant lower risk of ventricular arrhythmias and sudden death when compared with LGE+ cases. Patients with IP&LV-LGE had clinical characteristics and outcomes similar to the rest of LGE+ cases., Competing Interests: Conflict of interest: P.F.B. received a fellowship salary support grant from Alliance Medical. There is no other conflict of interest for the present study., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Heart failure (HF) is recognized as a global public health disease associated with high morbidity and mortality. It is suggested that the main underlying causes of HF in developing countries differ from those identified in well-resourced countries. This study therefore presents the cardiovascular risk factors and the underlying aetiology of HF among admitted patients in a teaching Hospital in Ghana., Method: The study prospectively recruited 140 consecutive patients admitted for heart failure at the Medical department of the Korle-Bu Teaching Hospital from March to October, 2014. The study evaluated the cardiovascular risk factors and the aetiologies of heart failure, and compared the risk factors and aetiologies with patient's age and gender., Results: The mean age of the study participants was 51.3 ± 16.8 years. The commonest cardiovascular risk factors observed were hypertension (46.5%), history of previous HF (40.7%), excessive alcohol use (38.6%), and family history of heart disease (29.3%); predominantly hypertension (68.3%). The major underlying aetiology of HF were dilated cardiomyopathy (38.6%), hypertensive heart disease (21.4%), ischaemic heart disease (13.6%) and valvular heart disease (12.9%). These underlying aetiology of HF were more common in patients aged 40 years and above (p = 0.004) and those presenting with multiple risk factors (p = 0.001)., Conclusion: The major underlying aetiology of heart failure in adults were dilated cardiomyopathy, hypertensive heart disease, ischaemic heart disease and valvular heart disease, which were significantly high among patients aged 40 years and above and those presenting multiple risk factors. Hypertension, excessive alcohol use, family history of heart disease and personal history of previous heart failure diagnosis are noted as the main cardiovascular risk factors among heart failure patients., (© 2023. The Author(s).)

Dilated cardiomyopathy (DCM) is an inevitable complication of Duchenne muscular dystrophy (DMD). Late gadolinium enhancement (LGE) demonstrated by cardiac MRI occurs in DMD-related DCM, indicating myocyte death and remodeling. We conducted a retrospective chart review identifying DMD patients in our center between January 2009 and July 2013. Subjects were cohorted by presence of LGE before age 14. We excluded patients in whom we could not determine LGE status prior to age 14. We reviewed comprehensive clinical data. Of the 41 subjects with complete data, 15 demonstrated LGE before age 14 ("early LGE") and 26 had no LGE by age 14 ("controls"). Those with early LGE exhibited a more rapid decline in LV fractional shortening (p = 0.028). Patients with early LGE were younger at age of initiation of ACE inhibition (p = 0.025), mineralocorticoid receptor antagonism (p = 0.0024), and beta-blockade (p = 0.0017), suggesting aggressive clinical management in response to abnormal MRI findings. There were no significant differences in LV dilation between the two groups (p = 0.1547). Early LGE was not associated with obesity (p = 0.32), age at loss of ambulation (p = 0.31), or heart rate (p-value > 0.8). Early onset of myocardial fibrosis as indicated by LGE on cardiac MRI is associated with earlier progression of cardiomyopathic changes despite earlier medication therapy. Identifying this risk factor, observed in 34% of our cohort during preadolescence, may guide medical therapy and early counseling about cardiomyopathy progression. We advocate for obtaining at least one MRI in patients with DMD prior to age 14 to risk stratify patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Competing interests: None declared.

Despite the emerging prevalence of left ventricular (LV) thrombus in dilated cardiomyopathy (DCM), clinical characteristics, management, and disease prognosis are poorly studied. We aim to assess the efficacy/safety profile of direct oral anticoagulants (DOACs) compared to warfarin by evaluating thrombus evolution, risk for stroke and systemic embolism (SSE), heart failure (HF) rehospitalization, all-cause mortality, and major adverse cardiovascular events (MACEs), and determine the impact of thrombus evolution on adverse events. We performed a historical cohort study of patients with a primary diagnosis of DCM and LV thrombus. Relationships between anticoagulants and thrombus resolution were analyzed with the Kaplan-Meier method and Cox regression. Associations between longitudinal thrombus evolution and adverse event hazard were measured with joint modeling. Among 122 patients included, 58.0% were prescribed warfarin, and 42.0% DOACs. Complete thrombus resolution at 90-day-after-index and 180-day-after-index was observed in 93 and 111 patients, with no difference in cumulative resolution between DOACs and warfarin. During a median follow-up of 12.5 months, MACE, all-cause death, SSE, and HF rehospitalization occurred in 42.6%, 27.9%, 4.1%, and 13.9% of patients, comparable in warfarin and DOACs groups. Thrombus persistence was associated with a higher risk of HF rehospitalization. Thrombus progression was associated with poor prognosis, with per unit increment in square-root-transformed thrombus-area resulting in a 1.0691-fold increase in MACE risk and a 1.0546-fold increase in death risk. This study suggests that in DCM patients with LV thrombus, DOACs were comparable to warfarin in thrombus resolution and safety profile. Thrombus persistence or progression was associated with an increased risk of HF rehospitalization, MACE, and mortality.

Background: In dilated cardiomyopathy (DCM), outcome after catheter ablation of ventricular tachycardia (VT) is modest, compared with ischemic heart disease (IHD). Pleomorphic VT (PL-VT) has been associated with fibrotic remodeling and end-stage heart failure in IHD. The prognostic role of PL-VT in DCM is unknown., Methods: Consecutive IHD (2009-2016) or DCM (2008-2018) patients undergoing ablation for monomorphic VT were included. PL-VT was defined as ≥1 spontaneous change of the 12-lead VT-morphology during the same induced VT episode. Patients were followed for VT recurrence and mortality., Results: A total of 247 patients (86% men; 63±13 years; IHD n=152; DCM n=95) underwent ablation for monomorphic VT. PL-VT was observed in 22 and 29 patients with IHD and DCM, respectively (14% versus 31%, P =0.003). In IHD, PL-VT was associated with lower LVEF (28±9% versus 34±12%, P =0.02) and only observed in those with LVEF<40%. In contrast, in DCM, PL-VT was not related to LVEF and induced in 27% of patients with LVEF>40%. During a median follow-up of 30 months, 79 (32%) patients died (IHD 48; DCM 31; P =0.88) and 120 (49%) had VT recurrence (IHD 59; DCM 61; P <0.001). PL-VT was associated with mortality in IHD but not in DCM. In IHD, VT recurrence was independently associated with LVEF, number of induced VTs, and procedural noncomplete success. Of note, in DCM, PL-VT (HR, 2.62 [95% CI, 1.47-4.69]), pathogenic mutation (HR, 2.13 [95% CI, 1.16-3.91]), and anteroseptal VT substrate (HR, 1.75 [95% CI, 1.00-3.07]) independently predicted VT recurrence., Conclusions: In IHD, PL-VT was associated with low LVEF and mortality. In DCM, PL-VT was not associated with mortality but a predictor of VT recurrence independent from LVEF. PL-VT in DCM may indicate a specific arrhythmic substrate difficult to control by current ablation techniques.

Sudden cardiac death (SCD) and significant ventricular arrhythmias in patients with dilated cardiomyopathy (DCM) have been markedly reduced over the last couple of decades as a result of the advances in pharmacological and non-pharmacological treatment. Primary prevention implantable cardioverter-defibrillator (ICD) plays an important role in the treatment of patients at risk of SCD caused by ventricular arrhythmias. However, the arrhythmic risk stratification in patients with DCM remains extremely challenging, and the decision for primary prevention ICD implantation based on left ventricular ejection fraction (LVEF) solely appears to be insufficient. This review provides an update on current evidence for primary prevention ICD implantation, arrhythmic risk stratification, and left ventricular reverse remodeling (LVRR) prediction in patients with DCM in addition to most recent guideline recommendations for primary prevention ICD implantation in DCM patients and a proposed multiparametric algorithm based on arrhythmic risk stratification and left ventricular reverse remodeling (LVRR) prediction to better identify patients who are likely to benefit from primary prevention ICD., (© 2022. The Author(s).)

Introduction: Nonischemic dilated cardiomyopathy (NIDCM) is a heterogeneous disease, and patients still have high risk of sudden cardiac death even after receiving treatment. The Selvester QRS score and the ESTIMATED score reported as predictors contain many variables and are complex to calculate. There is a need for a simple predictive score to accurately assess prognosis in clinical practice., Methods: A total of 953 elderly patients (age ≥60 years) diagnosed with NIDCM were enrolled from January 2010 to December 2019. In-hospital and long-term outcomes were studied., Results: Univariate logistic regression analysis showed that the AGEF score was associated with in-hospital mortality (OR: 1.828; 95% CI: 1.559-2.144; p < 0.001). Receiver operator characteristic curve analysis showed that the AGEF score was excellent at predicting clinical outcomes. The optimal cutoff value of the AGEF score for predicting long-term mortality was 2.50 (AUC = 0.743; 95% CI: 0.710-0.776; p < 0.001). Kaplan-Meier survival analysis showed that patients with an AGEF score >2.50 had a worse prognosis than those with an AGEF score ≤2.50 (log-rank χ2 103.69, p < 0.001). Moreover, multivariate Cox proportional hazard analysis showed that an AGEF score ≤2.50 was associated with a lower risk of long-term mortality in elderly patients with NIDCM (HR: 0.405; 95% CI: 0.310-0.529; p < 0.001)., Conclusions: The AGEF score could be considered as a simple and useful tool for risk stratification in elderly patients with NIDCM., (© 2022 S. Karger AG, Basel.)

Objectives: Serum chloride has a unique homeostatic role in modulating neurohormonal pathways. Some studies have reported that hypochloremia has potential prognostic value in cardiovascular diseases; thus, we aimed to investigate the association of baseline serum chloride with clinical outcomes in elderly patients with non-ischaemic dilated cardiomyopathy (NIDCM)., Design: Retrospective study., Setting and Participant: A total of 1088 patients (age ≥60 years) diagnosed with NIDCM were enrolled from January 2010 to December 2019., Results: Logistic regression analyses showed that serum chloride was significantly associated with in-hospital death. Receiver operating characteristic (ROC) curve analyses showed that serum chloride had excellent prognostic ability for in-hospital and long-term death (area under the curve (AUC)=0.690 and AUC=0.710, respectively). Kaplan-Meier survival analysis showed that the patients with hypochloremia had worse prognoses than those without hypochloremia (log-rank χ 2 =56.69, p<0.001). After adjusting for age, serum calcium, serum sodium, left ventricular ejection fraction, lg NT-proBNP and use of diuretics, serum chloride remained an independent predictor of long-term death (HR 0.934, 95% CI 0.913 to 0.954, p<0.001)., Conclusions: Serum chloride concentration was a prognostic indicator in elderly patients with NIDCM, and hypochloremia was significantly associated with both in-hospital and long-term poor outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Heart failure (HF) is a systemic inflammatory disease that causes hypotrophy and skeletal muscle loss. The Global Leadership Initiative on Malnutrition (GLIM) criteria have been developed as a novel evaluation index for malnutrition, with reported usefulness in HF caused by ischemic heart disease. However, reports on the usefulness of malnutrition evaluated by the GLIM criteria in non-ischemic dilated cardiomyopathy (NIDCM) and its relationship with psoas muscle volume are lacking. We investigated the prognostic value of malnutrition evaluated using the GLIM criteria and its association with psoas muscle volume in patients with NIDCM. We enrolled 139 consecutive patients with NIDCM between December 2000 and June 2020. Malnutrition was evaluated using the GLIM criteria on admission. The median follow-up period was 4.7 years. Cardiac events were defined as a composite of cardiac death, hospitalization for worsening HF, and lethal arrhythmia. Furthermore, we measured the psoas muscle volume using computed tomography volumetry in 48 patients. At baseline, the median age was 50 years, and 132 patients (95.0%) had New York Heart Association functional class I or II HF. The median psoas muscle volume was 460.8 cm 3 . A total of 26 patients (18.7%) were malnourished according to the GLIM criteria. The Kaplan-Meier survival analysis showed that malnourished patients had more cardiac events than non-malnourished patients (log-rank, P < 0.001). The multivariate Cox proportional hazards regression analysis revealed that GLIM criteria-based malnutrition was an independent determinant of cardiac events (hazard ratio, 2.065; 95% confidence interval, 1.166-3.656; P = 0.014). Psoas muscle volume, which was assessed in a total of 48 patients, was lower in malnourished than in non-malnourished patients (median, 369.0 vs. 502.3 cm 3 ; P = 0.035) and correlated with body mass index (r = 0.441; P = 0.002). Nutritional screening using the GLIM criteria may be useful in predicting future cardiac events in patients with NIDCM, reflecting a potential relationship between malnutrition and a low psoas muscle volume., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: Abnormal ventricular signals (AVS) are the cornerstone of substrate-based ventricular tachycardia (VT) ablation in sinus rhythm. Signal characterization of AVS in ischemic and nonischemic cardiomyopathies has never been performed., Objective: The purpose of this study was to describe ventricular signal abnormalities in 3 different pathologies and examine their association with the diastolic component of VT circuits., Methods: A total of 45 patients (15 ischemic cardiomyopathy [ICM], 15 arrhythmogenic cardiomyopathy [ACM], 15 dilated cardiomyopathy [DCM]) who had undergone VT ablation with >50% of the diastolic pathway of the VT circuit recorded were studied. AVS were classified into late potentials (LPs) and continuous fractionated ventricular signals (CFVS), and their characteristics and correlation with the diastolic pathway of VT circuits were analyzed., Results: Seventy-five VT circuits were analyzed. Bipolar scars were greatest in ICM endocardially (53 cm 2 ICM vs 36 cm 2 ACM vs 25 cm 2 DCM; P = .010) and in ACM epicardially (98 cm 2 ACM vs 25 cm 2 ICM vs 24 cm 2 DCM; P = .005). Location of the VT diastolic interval coincided with AVS location in 54% of VTs in ICM, 89% in ACM, and 72% in DCM (P = .036). There was a trend toward a greater association of diastolic intervals coinciding with LPs than with CFVS (78% vs 57%; P = .052) (69% diastolic intervals in ICM coincided with LPs, 33% with CFVS; P = .063). All patients (100%) with CFVS in ACM had VT diastolic components arising from CFVS (33% ICM, 64% DCM; P = .049). Positive predictive value for LPs vs CFVS was 77.8% vs 56.7%, and sensitivity was 67.3% vs 32.7%, respectively., Conclusion: The nature of abnormal signals in different cardiomyopathies reflects underlying pathology. LPs rather than CFVS seem to be more linked to diastolic components of VT circuits, especially in ICM. LPs have greater sensitivity and specificity for VT; however, CFVS may be of more relevance in ACM., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Alström syndrome is a rare, multisystemic genetic disorder, and dilated cardiomyopathy occurs in approximately two-thirds of patients with this condition. Because of donor organ shortage and unfavorable prognosis of multiple organ dysfunction, heart transplant is not the most desirable therapeutic option for patients with dilated cardiomyopathy with Alström syndrome. However, eliminating heart dysfunction elements at an appropriate time itself plays a pivotal role in preventing or even reversing other organ failures. Herein, we report the case of a 17-year-old boy who underwent successful isolated heart transplant despite severe liver dysfunction., Competing Interests: Disclosures All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: The present study aimed to evaluate the prognostic value of atrial strain and strain rate (SR) parameters derived from cardiac magnetic resonance (CMR) feature tracking (FT) in patients with ischaemic and non-ischaemic dilated cardiomyopathy with heart failure with reduced ejection fraction (HFrEF) but without atrial fibrillation., Methods and Results: A total of 300 patients who underwent CMR with left ventricular ejection fraction (LVEF) ≤ 40% and ischaemic or non-ischaemic dilated cardiomyopathy were analysed in this retrospective study. Major adverse cardiac events (MACEs) include cardiovascular death, heart transplantation, and rehospitalization for worsening HF. Ninety-four patients had MACEs during median follow-up of 3.84 years. Multivariate Cox regression models adjusted for common clinical and CMR risk factors detected a significant association between LA-εs and MACE in ischaemic (HR = 0.94/%; P = 0.002), non-ischaemic dilated cardiomyopathy (HR = 0.88/%; P = 0.001), or all included patients (HR = 0.87; P < 0.001). LA-εs provided incremental prognostic value over conventional outcome predictors (Uno C statistical comparison model: from 0.776 to 0.801, P < 0.0001; net reclassification improvement: 0.075, 95% CI: 0.0262-0.1301). Kaplan-Meier analysis revealed that the risk of MACE occurrence increased significantly with lower tertiles of left atrial reservoir strain (LA-εs) (log-rank P < 0.0001). Patients in the worst LA-εs tertile faced a significantly increased risk of MACEs irrespective of late gadolinium enhancement (LGE) (log-rank P < 0.0001)., Conclusions: LA-εs derived from CMR FT has a significant prognostic impact on patients with ischaemic or non-ischaemic dilated cardiomyopathy, incremental to common clinical and CMR risk-factors., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Clonal haematopoiesis of indeterminate potential (CHIP)-associated mutation is a risk factor for the development of ischaemic cardiomyopathy (ICM), but its association with non-ischaemic dilated cardiomyopathy (DCM) remains unclear. We aimed to determine the prevalence of CHIP in patients with DCM and define its risk for disease progression., Methods and Results: Next-generation sequencing targeting 54 common CHIP-associated genes was performed in 48 ICM and 52 DCM patients. The patients were monitored for a median of 3.1 years, and a COX proportional hazards model was used to examine the association between CHIP and adverse clinical outcome with regard to all-cause death or all-cause hospitalization. Overall, the prevalence of CHIP mutations was 19% and 13% in DCM and ICM, respectively. Seventeen per cent of ICM patients over 75 years were CHIP carriers. In DCM cohort, mutation event had already been observed in the patients who were under the age of 45 (13%). Among 54 genes analysed, DNMT3A had the highest mutation frequency, followed by TET2 and CUX1. Kaplan-Meier curve over a median of 3.1 year tracking period showed a trend towards poor clinical outcome in the DCM patients who carried DNMT3A or TET2 mutation; however, such association was not statistically significant., Conclusions: The prevalence of CHIP is detected at a young age in DCM, and accumulation of mutational frequency in DCM patients is independent of age. However, a larger patient cohort is required to validate the association between CHIP and clinical progression in the DCM patients., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Liver injury (LI) has been frequently observed in patients with dilated cardiomyopathy (DCM), whereas its prognostic value remains blurry. We attempted to appraise the prognostic effect of LI in patients with DCM., Methods: This retrospective study included 523 patients with DCM. LI was defined as a threefold increase in aspartate transaminase (≥ 135 U/L) or alanine transaminase (≥ 180 U/L) or a twofold increase in total bilirubin (≥ 41 umol/L) during hospitalization. The population was segmented into non-liver injury (NLI) group and LI group based on liver function test data. To balance differences in covariates at baseline, 1:1 propensity score matching (PSM) was performed., Results: Patients with LI had lower survival rate, compared with those with NLI (44.6% vs. 73.8%, P < 0.001). Similar results were also found in age (age > 50, 39.6% vs. 70.9%, P < 0.001; age ≤ 50, 51.3% vs. 79.5%, P < 0.001) and gender stratified analysis (male, 46.2% vs. 74.4%, P < 0.001; female 35.7% vs. 72.0%, P = 0.001). After PSM, the survival rate of patients with LI remained lower than those with NLI (44.6% vs. 64.1%, P = 0.019). Multivariable Cox regression analysis manifested that LI (hazard ratio [HR]: 1.692, 95% confidence interval [CI] 1.194-2.398, P = 0.003; HR: 1.675, 95% CI 1.078-2.604, P = 0.022, respectively) showed potent predictive effect on all-cause mortality in patients with DCM, both before and after PSM., Conclusions: The occurrence of LI herald adverse outcomes in patients with DCM and attention to LI may be conducive to risk stratification and management., (© 2022. The Author(s).)

Limb-girdle muscular dystrophy (LGMD) is a heterogeneous inherited disorder affecting the skeletal muscle and frequently also involve the heart and in LGMD; development of dilated cardiomyopathy is common and usually the predominant feature. Arrhythmias and conduction disease can be associated with the development of cardiomyopathy., (© 2022 Wiley Periodicals LLC.)

COVID-19 is a novel disease with multisystem involvement, but most patients have pulmonary and cardiovascular involvement in the acute stages. The cardiovascular impact of acute COVID-19 is well recognized and ranges from myocarditis, arrhythmias, and thrombotic occlusion of coronary arteries to spontaneous coronary artery dissection and microthrombi in small coronary vessels on autopsy. We report a case of a 37-year-old man who recovered from mild COVID-19 only to present a few weeks later with devastating cardiovascular involvement that included severe left ventricular impairment resulting from nonischemic cardiomyopathy, multiple left ventricular thrombi, and embolic stroke., (© 2022 by the Texas Heart® Institute, Houston.)

In patients admitted for heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and a concomitant supraventricular tachyarrhythmia (SVT) it is a challenge to predict LVEF recovery and differentiate tachycardia-induced cardiomyopathy (TIC) from dilated cardiomyopathy (DCM). The role of the electrocardiogram (ECG) and cardiac magnetic resonance (CMR) and in this acute setting remains unsettled. Forty-three consecutive patients admitted for HF due to SVT and LVEF < 50% undergoing CMR in the acute phase, were retrospectively included. Those who had LVEF > 50% at follow up were classified as TIC and those with LVEF < 50% were classified as DCM. Clinical, CMR and ECG findings were analyzed to predict LVEF recovery. Twenty-five (58%) patients were classified as TIC. Patients with DCM had wider QRS (121.2 ± 26 vs 97.7 ± 17.35 ms; p = 0.003). On CRM the TIC group presented with higher LVEF (33.4 ± 11 vs 26.9 ± 6.4%; p = 0.019) whereas late gadolinium enhancement (LGE) was more frequent in DCM group (61 vs 16%; p = 0.004). On multivariate analysis, QRS duration ≥ 100 ms (p = 0.027), LVEF < 40% on CMR (p = 0.047) and presence of LGE (p = 0.03) were independent predictors of lack of LVEF recovery. Furthermore, during follow-up (median 60 months) DCM patients were admitted more frequently for HF (44 vs 0%; p < 0.001) than TIC patients. In patients with reduced LVEF admitted for HF due to SVT, QRS ≥ 100 ms, LVEF < 40% and LGE are independently associated with lack of LVEF recovery and worse clinical outcome., (© 2022. Springer Japan KK, part of Springer Nature.)

Aims: While electrocardiogram (ECG) characteristics have been associated with life-threatening ventricular arrhythmias (LTVA) in dilated cardiomyopathy (DCM), they typically rely on human-derived parameters. Deep neural networks (DNNs) can discover complex ECG patterns, but the interpretation is hampered by their 'black-box' characteristics. We aimed to detect DCM patients at risk of LTVA using an inherently explainable DNN., Methods and Results: In this two-phase study, we first developed a variational autoencoder DNN on more than 1 million 12-lead median beat ECGs, compressing the ECG into 21 different factors (F): FactorECG. Next, we used two cohorts with a combined total of 695 DCM patients and entered these factors in a Cox regression for the composite LTVA outcome, which was defined as sudden cardiac arrest, spontaneous sustained ventricular tachycardia, or implantable cardioverter-defibrillator treated ventricular arrhythmia. Most patients were male (n = 442, 64%) with a median age of 54 years [interquartile range (IQR) 44-62], and median left ventricular ejection fraction of 30% (IQR 23-39). A total of 115 patients (16.5%) reached the study outcome. Factors F8 (prolonged PR-interval and P-wave duration, P < 0.005), F15 (reduced P-wave height, P = 0.04), F25 (increased right bundle branch delay, P = 0.02), F27 (P-wave axis P < 0.005), and F32 (reduced QRS-T voltages P = 0.03) were significantly associated with LTVA., Conclusion: Inherently explainable DNNs can detect patients at risk of LTVA which is mainly driven by P-wave abnormalities., Competing Interests: Conflicts of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Non-ischemic dilated cardiomyopathy is the most common subgroup of heart failure in young adults. Several metabolic defects could be the underlying etiology in these young heart failure patients. However, most cases are considered idiopathic. Primary carnitine deficiency is an overlooked inherited metabolic disease causing cardiomyopathy in these patients. Oral carnitine replacement therapy could prevent primary carnitine deficiency patients from progressing to advanced heart failure and life-threatening arrhythmias. In this case report, we present an index primary carnitine deficiency case and his brother's diagnosis and successful treatment period to draw attention to primary carnitine deficiency as a treatable cause of heart failure in young adults.

Aims: The role of necroptosis in dilated cardiomyopathy (DCM) remains unclear. Here, we examined whether phosphorylation of mixed lineage kinase domain-like protein (MLKL), an indispensable event for execution of necroptosis, is associated with the progression of DCM., Methods and Results: Patients with DCM (n = 56, 56 ± 15 years of age; 68% male) were enrolled for immunohistochemical analyses of biopsies. Adverse events were defined as a composite of death or admission for heart failure or ventricular arrhythmia. Compared with the normal myocardium, increased signals of MLKL phosphorylation were detected in the nuclei, cytoplasm, and intercalated discs of cardiomyocytes in biopsy samples from DCM patients. The phosphorylated MLKL (p-MLKL) signal was increased in enlarged nuclei or nuclei with bizarre shapes in hypertrophied cardiomyocytes. Nuclear p-MLKL level was correlated negatively with septal peak myocardial velocity during early diastole (r = -0.327, P = 0.019) and was correlated positively with tricuspid regurgitation pressure gradient (r = 0.339, P = 0.023), while p-MLKL level in intercalated discs was negatively correlated with mean left ventricular wall thickness (r = -0.360, P = 0.014). During a median follow-up period of 3.5 years, 10 patients (18%) had adverse events. To examine the difference in event rates according to p-MLKL expression levels, patients were divided into two groups by using the median value of nuclear p-MLKL or intercalated disc p-MLKL. A group with high nuclear p-MLKL level (H-nucMLKL group) had a higher adverse event rate than did a group with low nuclear p-MLKL level (L-nucMLKL group) (32% vs. 4%, P = 0.012), and Kaplan-Meier survival curves showed that the adverse event-free survival rate was lower in the H-nucMLKL group than in the L-nucMLKL group (P = 0.019 by the log-rank test). Such differences were not detected between groups divided by a median value of intercalated disc p-MLKL. In δ-sarcoglycan-deficient (Sgcd -/- ) mice, a model of DCM, total p-MLKL and nuclear p-MLKL levels were higher than in wild-type mice., Conclusion: The results suggest that increased localization of nuclear p-MLKL in cardiomyocytes is associated with left ventricular diastolic dysfunction and future adverse events in DCM., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The potential utility of nifekalant, a new Class III antiarrhythmic drug, to offer long-term protection against ventricular arrhythmia has been investigated in this case report. A 44-year-old male patient with dilated cardiomyopathy complicated with heart failure and persistent ventricular tachycardia was treated with nifekalant. The patient was treated with nifekalant for 31 days, which effectively terminated ventricular tachycardia and maintained sinus rhythm, with no clinical adverse reactions. After heart transplantation, postoperative follow-up showed good cardiac function and no arrhythmia. On the basis of nifekalant's working mechanism, there is a good chance that it can cure ventricular arrhythmia on a long-term basis.