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Left bundle branch block (LBBB) is a frequent finding in patients with heart failure (HF), particularly in those with dilated cardiomyopathy (DCM). LBBB has been commonly described as a consequence of DCM development. However, a total recovery of left ventricular (LV) function after cardiac resynchronization therapy (CRT), observed in patients with LBBB and DCM, has led to increasing acknowledgement of LBBB-induced dilated cardiomyopathy (LBBB-iDCM) as a specific pathological entity. Its recognition has important clinical implications, as LBBB-iDCM patients may benefit from an early CRT strategy rather than medical HF therapy only. At present, there are no definitive diagnostic criteria enabling the universal identification of LBBB-iDCM, and no defined therapeutic approach in this subgroup of patients. This review compiles the main findings about LBBB-iDCM pathophysiology and the current proposed diagnostic criteria and therapeutic approach., (Copyright © 2024 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

A 39-year-old woman with intermittent palpitations, psoriasis, and a family history of sudden death presented with dilated right heart chambers and an enlarged coronary sinus. Despite a normal bubble study, further evaluation with transesophageal echocardiography revealed an abnormal pulmonary venous return: the left pulmonary veins drained into the coronary sinus. Cardiac computed tomography confirmed this finding, suggesting a partial abnormal pulmonary venous return as the underlying issue. Cardiac catheterization indicated increased pulmonary artery flow with normal pulmonary vascular resistance. The patient was referred for surgery. In this pathway involving the differential diagnosis of right heart dilatation, despite a confusing history and conflicting findings, echocardiographic clues led to the diagnosis., (© 2024 Wiley Periodicals LLC.)

Background: Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome, affecting over 80% of individuals with this condition. This syndrome is characterized by a triad of myxomas, skin pigmentation, and endocrine hyperfunction, featuring multiple endocrine neoplasms with skin and cardiac involvement. Dilated cardiomyopathy, a primary cardiomyopathy, is defined as the dilation and impaired systolic function of the left or both ventricles. Its clinical presentation varies from being asymptomatic to heart failure or sudden cardiac death, making it a leading global cause of heart failure. Currently, Dilated cardiomyopathy has an estimated prevalence of 1/2500-1/250 individuals, predominantly affecting those aged 30-40 years, with a male-to-female ratio of 3:1. This case report describes a heart failure patient with cardiac myxoma caused by Carney syndrome combined with dilated cardiomyopathy. The patient was successfully treated for heart failure by heart transplantation., Case Presentation: Herein, we report a case of heart failure due to Carney syndrome that resulted in cardiac myxoma combined with dilated cardiomyopathy. A 35-year-old male was admitted to the hospital three years ago because of sudden chest tightness and shortness of breath. Echocardiography indicated myxoma, and a combination of genetic screening and physical examination confirmed Carney syndrome with cardiac myxoma. Following symptomatic management, he was discharged. Surgical interventions were not considered at the time. However, the patient's chest tightness and shortness of breath symptoms worsened, and he returned to the hospital. A New York Heart Association grade IV heart function was confirmed, and echocardiography indicated the presence of dilated cardiomyopathy accompanied by cardiac myxoma. Ultimately, the patient's heart failure was successfully treated with heart transplantation., Conclusions: Cardiac myxoma caused by Carney syndrome combined with heart failure caused by dilated cardiomyopathy can be resolved by heart transplantation., (© 2024. The Author(s).)

Arrhythmias frequently accompany heart failure and left ventricular dysfunction. Tachycardias, atrial fibrillation, and premature ventricular contractions can induce a reversible form of dilated cardiomyopathy (CM) known as arrhythmia-induced CM (AiCM). The intriguing question is why certain individuals are more susceptible to AiCM, despite similar arrhythmia burdens. The primary challenge is determining the extent of arrhythmias' contribution to left ventricular systolic dysfunction. AiCM should be considered in patients with a mean heart rate of >100 beats/min, atrial fibrillation, or a PVC burden of >10%. Confirmation of AiCM occurs when CM reverses upon eliminating the responsible arrhythmia. Therapy choice depends on the specific arrhythmia, patient comorbidities, and preferences. After left ventricular function is restored, ongoing follow-up is essential if an abnormal myocardial substrate persists. Accurate diagnosis and treatment of AiCM have the potential to enhance patients' quality of life, improve clinical outcomes, and reduce hospital admissions and overall health care costs., Competing Interests: Funding Support and Author Disclosures Funded by NIH/NHLBI 1R01HL139874-01 (PI: Dr Huizar), VA Merit BX004861-01 (PI: Dr Huizar). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Background: Dilated cardiomyopathy (DCMP) is characterized by the enlargement and weakening of the heart and is a major cause of heart failure in children. Infection and nutritional deficiencies are culprits for DCMP. Zinc is an important nutrient for human health due to its anti-oxidant effect that protects cell against oxidative damage. This case-control study aimed to investigate the relationship between dietary intake of zinc and selenium and the risk of DCMP in pediatric patients., Methods: A total of 36 DCMP patients and 72 matched controls were recruited, and their dietary intakes were assessed via a validated food frequency questionnaire. We used chi-square and sample T-test for qualitative and quantitative variables, respectively. Logistic regression analysis was applied to assess the relationship between selenium and zinc intake with the risk of DCMP., Results: After fully adjusting for confounding factors, analyses showed that selenium (OR = 0.19, CI = 0.057-0.069, P trend < 0.011) and zinc (OR = 0.12, CI = 0.035-0.046, P trend < 0.002) intake were strongly associated with 81% and 88% lower risk of pediatric DCMP, respectively., Conclusions: This study highlights the protective role of adequate dietary intake of selenium and zinc in decreasing the risk of DCMP in children. Malnutrition may exacerbate the condition and addressing these micronutrient deficiencies may improve the cardiac function. Further studies are recommended to detect the underlying mechanisms and dietary recommendations for DCMP prevention., (© 2024. The Author(s).)

Background: Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle weakness due to the absence of functional dystrophin. DMD patients also develop dilated cardiomyopathy (DCM). We have previously shown that DMD (mdx) mice and a canine DMD model (GRMD) exhibit abnormal intracellular calcium (Ca 2+ ) cycling related to early-stage pathological remodelling of the ryanodine receptor intracellular calcium release channel (RyR2) on the sarcoplasmic reticulum (SR) contributing to age-dependent DCM., Methods: Here, we used hiPSC-CMs from DMD patients selected by Speckle-tracking echocardiography and canine DMD cardiac biopsies to assess key early-stage Duchenne DCM features., Results: Dystrophin deficiency was associated with RyR2 remodelling and SR Ca 2+ leak (RyR2 Po of 0.03 ± 0.01 for HC vs. 0.16 ± 0.01 for DMD, P < 0.01), which led to early-stage defects including senescence. We observed higher levels of senescence markers including p15 (2.03 ± 0.75 for HC vs. 13.67 ± 5.49 for DMD, P < 0.05) and p16 (1.86 ± 0.83 for HC vs. 10.71 ± 3.00 for DMD, P < 0.01) in DMD hiPSC-CMs and in the canine DMD model. The fibrosis was increased in DMD hiPSC-CMs. We observed cardiac hypocontractility in DMD hiPSC-CMs. Stabilizing RyR2 pharmacologically by S107 prevented most of these pathological features, including the rescue of the contraction amplitude (1.65 ± 0.06 μm for DMD vs. 2.26 ± 0.08 μm for DMD + S107, P < 0.01). These data were confirmed by proteomic analyses, in particular ECM remodelling and fibrosis., Conclusions: We identified key cellular damages that are established earlier than cardiac clinical pathology in DMD patients, with major perturbation of the cardiac ECC. Our results demonstrated that cardiac fibrosis and premature senescence are induced by RyR2 mediated SR Ca 2+ leak in DMD cardiomyocytes. We revealed that RyR2 is an early biomarker of DMD-associated cardiac damages in DMD patients. The progressive and later DCM onset could be linked with the RyR2-mediated increased fibrosis and premature senescence, eventually causing cell death and further cardiac fibrosis in a vicious cycle leading to further hypocontractility as a major feature of DCM. The present study provides a novel understanding of the pathophysiological mechanisms of the DMD-induced DCM. By targeting RyR2 channels, it provides a potential pharmacological treatment., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare.

Background: Heart transplantation (HT) is the only option for most patients with end-stage heart failure and hypertrophic cardiomyopathy (HCM) who fail medical therapy. Data on the long-term outcomes post-transplant in HCM individuals remain scarce., Methods: We analyzed data of 319 adult patients who underwent HT between 1984 and 2019. Patients were followed for cardiac allograft rejection, cardiac allograft vasculopathy (CAV), death, or re-transplantation., Results: Outcomes of 24 patients with HCM, 160 with ischemic, and 135 with dilated cardiomyopathy were compared. During a mean follow-up of 11.6 ± 7.2 (max 27.8), 16.7 ± 8.2 (max 32.7), and 16.1 ± 9.7 (max 34.6) years after HT in hypertrophic, ischemic, and dilated cardiomyopathy groups, respectively: 10-year survival rate was 67%, 62%, 69%, respectively (p = .04). Post-transplantation, HCM individuals more often than the other two studied groups required prolonged inotropic support (37%, 12%, 17%, respectively, p = .02), temporary mechanical circulatory support (45%, 13%, 14%, respectively, p < .01), and renal replacement therapy immediately post-HT (55%, 19%, 24%, respectively, p < .01). No significant inter-group differences were noted in the 10-year freedom from acute allograft rejection (38%, 46%, 43%, respectively, p = .38) or 10-year freedom from CAV (88%, 78%, 81%, respectively, p = .57)., Conclusions: The long-term post-transplant prognosis of adult patients with hypertrophic cardiomyopathy is favorable despite more challenging immediate post-HT course., (© 2024 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Aims: Cardiomyopathies (CMPs) are a heterogeneous group of diseases that are defined by structural and functional abnormalities of the cardiac muscle. Dilated cardiomyopathy (DCM), the most common CMP, is defined by left ventricular dilation and impaired contractility and represents a common cause of heart failure. Different phenotypes result from various underlying genetic and acquired causes with variable effects on disease development and progression, prognosis, and response to medical treatment. Current treatment algorithms do not consider these different aetiologies, due to lack of insights into treatable drivers of cardiac failure in patients with DCM. Our study aims to precisely phenotype and genotype the various subtypes of DCM and hereby lay the foundation for individualized therapy., Methods and Results: The Geno- And Phenotyping of PrImary Cardiomyopathy (GrAPHIC) is a currently ongoing prospective observational monocentric cohort study that recruits patients with DCM after exclusion of other causes such as coronary artery disease, valvular dysfunction, myocarditis, exposure to toxins, and peripartum CMP. Patients are enrolled at our heart failure outpatient clinic or during hospitalization at the University Hospital Hamburg. Clinical parameters, multimodal imaging and functional assessment, cardiac biopsies, and blood samples are obtained to enable an integrated genomic, functional, and biomarker analysis., Conclusions: The GrAPHIC will contribute to a better understanding of the heterogeneous nature of primary CMPs focusing on DCM and provide improved prognostic approaches and more individualized therapies., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Psoriasis is a chronic inflammatory skin disease with a genetic basis. Psoriasis is accepted as a systemic, immune-mediated disease. Hypertension, obesity, metabolic disorders including diabetes mellitus and hyperlipidemia, and psychiatric disorders are more prevalent among children with psoriasis compared to children without psoriasis. In this study, we report a case of dramatic response of inflammatory cardiomyopathy to anti-inflammatory treatment of psoriasis; which might reveal similar pathogenesis basis of these two diseases., Case Presentation: A 9-year-old Caucasian boy presenting with signs and symptoms of heart failure refractory to conventional therapies was admitted to our pediatric cardiology service. As the patient also had psoriasis, and considering the fact that there might be an association between the two conditions, immunosuppressive drugs were administered, which led to a dramatic improvement in heart function., Conclusions: The results of this study add to evidence linking psoriasis with inflammatory dilated cardiomyopathy. Clinicians, particularly cardiologists, must pay special attention to the cardiac complications of systemic diseases., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Duchenne muscular dystrophy is a fatal X-linked recessive disease affecting approximately 1 in 3500 births. It is characterized by a genetic lack of dystrophin, which is an essential protein for maintaining muscle integrity. The lack of dystrophin plays a pathophysiological role in the development of dilated cardiomyopathy in Duchenne muscular dystrophy. Currently, no consensus exists on specific pharmacological therapy guidelines for these patients; however, it centers around the guidelines for heart failure management. This systematic review investigated 12 randomized control trials dating back to 2005 in the pharmacotherapy of patients with dilated cardiomyopathy Duchenne muscular dystrophy. This review specifically included angiotensin-converting enzyme inhibitors, aldosterone receptor blockers, angiotensin receptor/neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. Despite their limitations, these studies have shown promising effects in improving the overall heart function and prognosis in patients with this condition. However, to attain higher statistical significance, future studies should investigate larger populations and for longer periods., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Multisystem inflammatory syndrome in children (MIS-C) is a rare post-infectious complication associated with COVID-19. This case report presents a detailed account of a paediatric patient diagnosed with MIS-C who developed dilated cardiomyopathy as a significant complication. This report aims to enhance our understanding of the rare potential cardiovascular implications of MIS-C and highlights the importance of prompt recognition and management., (© 2023 Vipulkumar V. G., et al.)

Lyme carditis is a well-established manifestation of early disseminated Lyme infection, yet the relationship between late disseminated Lyme disease and the development of dilated cardiomyopathy (DCM) remains unclear. The present systematic review aims to summarize existing literature on the association between late disseminated Lyme disease and DCM. A systematic review was conducted in PubMed, Embase, CENTRAL, and MEDLINE databases, after which a total of 11 observational studies (n = 771) were ultimately included for final data extraction. Although most studies (7/11) identified evidence associating Borrelia-infection with DCM, further research is required to isolate late disseminated Borrelia infection as a causative agent of DCM., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Diagnosis of acute myocarditis or dilated cardiomyopathy (DCM) on initial presentation is difficult in children younger than 2 years because most present with complaints suggestive of a respiratory infection. The objective of this study is to determine whether signs, symptoms, and diagnostic studies excluding those of heart failure, done routinely in the emergency department could distinguish children younger than 2 years with acute myocarditis or DCM from those with respiratory illnesses., Methods: Sixty-four infants' charts, 32 cases and 32 controls, were reviewed from January 1, 2009, through December 31, 2020. Controls were matched to cases with respect to age, reason, and time of admission. Signs, symptoms, and blood gases were reviewed., Results: The median age is 6.5 (0.5-22) months in both groups. Infants presenting with signs of heart failure including murmurs ( P = 0.002), prolonged capillary refill ( P = 0.024), cool, mottled extremities ( P = 0.002), poor perfusion ( P = 0.001), or hepatomegaly ( P < 0.001) were more likely to be diagnosed with acute myocarditis or DCM when compared with the control group with respiratory disease. Infants with fever ( P = 0.017), nasal congestion ( P < 0.001), rhinorrhea ( P < 0.001), cough ( P < 0.001), and wheezing ( P < 0.001) were more likely to have a respiratory illness than acute myocarditis or DCM. The presence of a lower p co2 (30 [14-116] vs 40 [31-59] mm Hg, P < 0.001), lower bicarbonate (16.7 [6.3-23.4] vs 21.7 [16-28.4], P < 0.001), or an oxygen saturation > 95% ( P = 0.004) was observed in infants with acute myocarditis or DCM compared with those with respiratory illness. By multivariable analysis, infants with tachycardia in the absence of fever, metabolic acidosis, and an oxygen saturation > 95% were more likely to have acute myocarditis or DCM than those without this disease., Conclusions: Children younger than 2 years presenting to the emergency department with tachycardia and no fever, metabolic acidosis, and a high oxygen saturation should be investigated for acute myocarditis or DCM., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Dilated cardiomyopathy is conventionally defined as the presence of left ventricular or biventricular dilatation or systolic dysfunction in the absence of abnormal loading conditions (eg, primary valve disease) or significant coronary artery disease sufficient to cause ventricular remodelling. This definition has been recognised as overly restrictive, as left ventricular hypokinesis without dilation could be the initial presentation of dilated cardiomyopathy. The causes of dilated cardiomyopathy comprise genetic (primary dilated cardiomyopathy) or acquired factors (secondary dilated cardiomyopathy). Acquired factors include infections, toxins, cancer treatment, endocrinopathies, pregnancy, tachyarrhythmias, and immune-mediated diseases. 5-15% of patients with acquired dilated cardiomyopathy harbour a likely pathogenic or pathogenic gene variant (ie, gene mutation). Therefore, the diagnostic tests and therapeutic approach should always consider both genetic and acquired factors. This Seminar will focus on the current multidimensional diagnostic and therapeutic approach and discuss the underlying pathophysiology that could drive future treatments aiming to repair or replace the existing gene mutation, or target the specific inflammatory, metabolic, or pro-fibrotic drivers of genetic or acquired dilated cardiomyopathy., Competing Interests: Declaration of interests SH receives personal fees for independent scientific advice on early development in the field of heart failure for AstraZeneca, Ribocure, and CSL Behring, and receives research support from AstraZeneca and CSL Behring; acknowledges support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, Dutch Cardiovascular Alliance CVON2016-Early HFPEF 2015–10, CVON She-PREDICTS grant 2017–21, CVON Arena-PRIME 2017–18, and DCVA-Double Dosis 2020-B005; receives funding from IMI2-CARDIATEAM (821508); and is a member of the European Reference Network for rare, low prevalence, and complex diseases of the heart (ERN GUARD-Heart). NKL receives unrestricted research support from Pfizer and the O’Hare and Steggall Family Foundations, and receives modest consulting incomes from Pfizer, Bristol Myers Squibb, Cytokinetics, and Tenaya. CT has received speaker fees or contributions to congresses from Bristol Myers Squibb and Pfizer. KK received moderate speaker fees from Pfizer and Alnylam. We acknowledge funding from the German Research Foundation (Deutsche Forschungsgemeinschaft) with the Collaborative Research Center 1470 (Project B02) to CT and from the Deutsche Herzstiftung (COVID-19) to KK., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Detailed assessments of whole heart mechanics are crucial for understanding the consequences of sarcomere perturbations that lead to cardiomyopathy in mice. Echocardiography offers an accessible and cost-effective method of obtaining metrics of cardiac function, but the most routine imaging and analysis protocols might not identify subtle mechanical deficiencies. This study aims to use advanced echocardiography imaging and analysis techniques to identify previously unappreciated mechanical deficiencies in a mouse model of dilated cardiomyopathy (DCM) before the onset of overt systolic heart failure (HF). Mice lacking muscle LIM protein expression (MLP -/- ) were used to model DCM-linked HF pathogenesis. Left ventricular (LV) function of MLP -/- and wild-type (WT) controls were studied at 3, 6, and 10 wk of age using conventional and four-dimensional (4-D) echocardiography, followed by speckle-tracking analysis to assess torsional and strain mechanics. Mice were also studied with RNA-seq. Although 3-wk-old MLP -/- mice showed normal LV ejection fraction (LVEF), these mice displayed abnormal torsional and strain mechanics alongside reduced β-adrenergic reserve. Transcriptome analysis showed that these defects preceded most molecular markers of HF. However, these markers became upregulated as MLP -/- mice aged and developed overt systolic dysfunction. These findings indicate that subtle deficiencies in LV mechanics, undetected by LVEF and conventional molecular markers, may act as pathogenic stimuli in DCM-linked HF. Using these analyses in future studies will further help connect in vitro measurements of the sarcomere function to whole heart function. NEW & NOTEWORTHY A detailed study of how perturbations to sarcomere proteins impact whole heart mechanics in mouse models is a major yet challenging step in furthering our understanding of cardiovascular pathophysiology. This study uses advanced echocardiographic imaging and analysis techniques to reveal previously unappreciated subclinical whole heart mechanical defects in a mouse model of cardiomyopathy. In doing so, it offers an accessible set of measurements for future studies to use when connecting sarcomere and whole heart function.

Background Among patients with an implantable cardioverter-defibrillator, a high prevalence of atrial fibrillation (AF) is present. Identification of AF predictors in this patient group is of clinical importance to initiate appropriate preventive therapeutic measures to reduce the risk of AF-related complications. This study assesses whether cardiac magnetic resonance imaging-derived atrial characteristics are associated with AF development in patients with a dual-chamber implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator, as detected by the cardiac implantable electronic device. Methods and Results This single-center retrospective study included 233 patients without documented AF history at the moment of device implantation (dual-chamber implantable cardioverter-defibrillator [63.5%] or cardiac resynchronization therapy defibrillator [36.5%]). All patients underwent cardiac magnetic resonance imaging before device implantation. Cardiac magnetic resonance-derived features of left atrial (LA) remodeling were evaluated in all patients. Detection of AF episodes was based on cardiac implantable electronic device interrogation. During a median follow-up of 6.1 years, a newly diagnosed AF episode was detected in 88 of the 233 (37.8%) patients with an ICD. In these patients, increased LA volumes and impaired LA function (LA emptying fraction and LA strain) were found as compared with patients without AF during follow-up. However, a significant association was only found in patients with dilated cardiomyopathy and not in patients with ischemic cardiomyopathy. Conclusions LA remodeling characteristics were associated with development of AF in patients with dilated cardiomyopathy but not patients with ischemic cardiomyopathy, suggesting different mechanisms of AF development in ischemic cardiomyopathy and dilated cardiomyopathy. Assessment of LA remodeling before device implantation might identify high-risk patients for AF.

A 56-year-old woman was referred to our hospital for the further evaluation of drug-refractory heart failure with a reduced ejection fraction. A family history interview revealed that men in her family had died of Duchenne muscular dystrophy (DMD), whereas she had no skeletal muscle disorder. Myocardial histopathology revealed a reduced dystrophin expression in the cardiomyocyte membrane, and a dystrophin (DMD) gene analysis identified a duplication in exon 8-9 on Xp21, suggesting that she had a cardiac-specific phenotype of dystrophinopathy, i.e. X-linked dilated cardiomyopathy (XLDCM). In conclusion, careful family history interviews and an investigation of dystrophinopathy are required to detect XLDCM in women.

What Is This Plain Language Summary About?: This summary explains the results of a long-term extension study on the effects of a specific medicine. A long-term extension study allows people who have already completed a research study to continue taking treatment. Researchers can then look at how a treatment works over a long period of time. This extension study looked at the effects of a medicine called ARRY-371797 (also known as PF-07265803) in people with dilated cardiomyopathy (DCM for short) caused by a faulty lamin A/C gene (also known as the LMNA gene). This condition is called LMNA-related DCM. In people with LMNA-related DCM, the heart muscle becomes thinner and weaker than normal. This can lead to heart failure, where the heart is unable to pump enough blood around the body. The extension study allowed people who had completed an earlier 48-week study to continue taking ARRY-371797 for another 96 weeks (around 22 months)., What Were the Results of the Extension Study?: 8 people joined the extension study and continued with the dose of ARRY-371797 that they had taken in the first study. This means that people could have taken ARRY-371797 continuously for up to 144 weeks (around 2 years and 9 months). Using the 6-minute walk test (6MWT for short), researchers regularly checked people taking ARRY-371797 to see how far they could walk. Throughout the extension study, people were able to walk further than they could before they started taking ARRY-371797. This suggests that people could maintain the improvements in their ability to do daily activities with long-term ARRY-371797 treatment. Researchers also looked at how severe people's heart failure was by using a test that measures levels of a biomarker called NT-proBNP. A biomarker is something found in the body that can be measured to indicate the extent of a disease. Throughout this study, the levels of NT-proBNP in people's blood was lower than before they started taking ARRY-371797. This suggests that they maintained stable heart function. Using the Kansas City Cardiomyopathy Questionnaire (KCCQ for short), researchers asked people about their quality of life, and if they experienced any side effects. A side effect is something that people feel while taking a treatment. Researchers evaluate if a side effect is related to the treatment or not. Some improvement in KCCQ response during the study was seen, although results were varied. There were no serious side effects that were considered related to treatment with ARRY-371797., What Do the Results of the Extension Study Mean?: Researchers found that the improvements in functional capacity and heart function seen with ARRY-371797 treatment in the original study were maintained with long-term treatment. Larger studies are needed to determine if ARRY-371797 could be an effective treatment for people with LMNA-related DCM. One such study (called REALM-DCM) was started in 2018 but ended early, as it was unlikely to show a clear treatment benefit of ARRY-371797. Phase 2 long-term extension study (NCT02351856) Phase 2 study (NCT02057341) Phase 3 REALM-DCM study (NCT03439514).

Group B enteroviruses, including coxsackievirus B3 (CVB3), can persistently infect cardiac tissue and cause dilated cardiomyopathy. Persistence is linked to 5' terminal deletions of viral genomic RNAs that have been detected together with minor populations of full-length genomes in human infections. In this study, we explored the functions and interactions of the different viral RNA forms found in persistently infected patients and their putative role(s) in pathogenesis. Since enterovirus cardiac pathogenesis is linked to the viral proteinase 2A, we investigated the effect of different terminal genomic RNA deletions on 2A activity. We discovered that 5' terminal deletions in CVB3 genomic RNAs decreased the levels of 2A proteinase activity but could not abrogate it. Using newly generated viral reporters encoding nano-luciferase, we found that 5' terminal deletions resulted in decreased levels of viral protein and RNA synthesis in singly transfected cardiomyocyte cultures. Unexpectedly, when full-length and terminally deleted forms were cotransfected into cardiomyocytes, a cooperative interaction was observed, leading to increased viral RNA and protein production. However, when viral infections were carried out in cells harboring 5' terminally deleted CVB3 RNAs, a decrease in infectious particle production was observed. Our results provide a possible explanation for the necessity of full-length viral genomes during persistent infection, as they would stimulate efficient viral replication compared to that of the deleted genomes alone. To avoid high levels of viral particle production that would trigger cellular immune activation and host cell death, the terminally deleted RNA forms act to limit the production of viral particles, possibly as trans -dominant inhibitors. IMPORTANCE Enteroviruses like coxsackievirus B3 are able to initiate acute infections of cardiac tissue and, in some cases, to establish a long-term persistent infection that can lead to serious disease sequelae, including dilated cardiomyopathy. Previous studies have demonstrated the presence of 5' terminally deleted forms of enterovirus RNAs in heart tissues derived from patients with dilated cardiomyopathy. These deleted RNAs are found in association with very low levels of full-length enterovirus genomic RNAs, an interaction that may facilitate continued persistence while limiting virus particle production. Even in the absence of detectable infectious virus particle production, these deleted viral RNA forms express viral proteinases at levels capable of causing viral pathology. Our studies provide mechanistic insights into how full-length and deleted forms of enterovirus RNA cooperate to stimulate viral protein and RNA synthesis without stimulating infectious viral particle production. They also highlight the importance of targeting enteroviral proteinases to inhibit viral replication while at the same time limiting the long-term pathologies they trigger.

Dilated cardiomyopathy (DCM) is distinguished by ventricular chamber expansion, systolic dysfunction, and normal left ventricular (LV) wall thickness, and is mainly caused due to genetic or environmental factors; however, its aetiology is undetermined in the majority of patients. The focus of this work is on pathogenesis, small animal models, as well as the herbal medicinal approach, and the most recent advances in imaging modalities for patients with dilated cardiomyopathy. Several small animal models have been proposed over the last few years to mimic various pathomechanisms that contribute to dilated cardiomyopathy. Surgical procedures, gene mutations, and drug therapies are all characteristic features of these models. The pros and cons, including heart failure stimulation of extensively established small animal models for dilated cardiomyopathy, are illustrated, as these models tend to procure key insights and contribute to the development of innovative treatment techniques for patients. Traditional medicinal plants used as treatment in these models are also discussed, along with contemporary developments in herbal therapies. In the last few decades, accurate diagnosis, proper recognition of the underlying disease, specific risk stratification, and forecasting of clinical outcome, have indeed improved the health of DCM patients. Cardiac magnetic resonance (CMR) is the bullion criterion for assessing ventricular volume and ejection fraction in a reliable and consistent direction. Other technologies, like strain analysis and 3D echocardiography, have enhanced this technique's predictive and therapeutic potential. Nuclear imaging potentially helps doctors pinpoint the causative factors of left ventricular dysfunction, as with cardiac sarcoidosis and amyloidosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Dilated cardiomyopathy (DCM) is typically defined by left ventricular dilation and systolic dysfunction in the absence of a clear precipitant. Idiopathic disease is common; up to 50% of patients with DCM have no cause found despite imaging, genetic and biopsy assessments. Treatment remains focused on managing symptoms, reducing the risk of sudden cardiac death and ameliorating the structural and electrical complications of disease progression. In the absence of aetiology-specific treatments, the condition remains associated with a poor prognosis; mortality is approximately 40% at 10 years. The role of immune-mediated inflammatory injury in the development and progression of DCM was first proposed over 30 years ago. Despite the subsequent failures of three large clinical trials of immunosuppressive treatment (ATTACH, RENEWAL and the Myocarditis Treatment Trial), evidence for an abnormal adaptive immune response in DCM remains significant. In this review, we summarise and discuss available evidence supporting immune dysfunction in DCM, with a specific focus on cellular immunity. We also highlight current clinical and experimental treatments. We propose that the success of future immunosuppressive treatment trials in DCM will be dependent on the deep immunophenotyping of patients, to identify those with active inflammation and/or an abnormal immune response who are most likely to respond to therapy., (© 2022 The Association for the Publication of the Journal of Internal Medicine.)

Dilated cardiomyopathy is defined by the presence of left ventricular dilatation and contractile dysfunction in the absence of abnormal loading conditions and severe coronary artery disease. Once dilated cardiomyopathy is discovered, a careful and detailed history with laboratory tests may reveal a potential toxic cause. In this article, we present the case of a patient with suspected toxic dilated cardiomyopathy, and then discuss the common causes and treatment of toxic dilated cardiomyopathy., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Coronary artery disease of non-atherosclerotic aetiology, while rare in incidence, can have a wide aetiology, such as fibromuscular dysplasia, which is a non-inflammatory arteriopathy of numerous histopathological types of fibromuscular tissue accumulation. This brief report describes the case of a 22-year-old male with a recently developed dilated cardiomyopathy and a history of aborted cardiac arrest at the age of 14 years. Coronary angiogram revealed severe three vessels disease, while optical coherence tomography established fibromuscular dysplasia as aetiology. Balloon and stent angioplasty was performed guided by fractional flow reserve with acceptable angiographic result.

Background: Von Hippel-Lindau (VHL) syndrome is an autosomal dominant hereditary disease affecting multiple organs, with pheochromocytoma in 26% of cases. However, VHL syndrome with congestive heart failure and dilated cardiomyopathy as the primary clinical manifestations has been rarely reported., Case Presentation: A 35-year-old male patient was admitted to the hospital with dyspnea. The patient had a history of cerebellar hemangioblastoma that had been resected, and a one-year history of hypertension. Echocardiography and cardiac magnetic resonance imaging demonstrated a dilated left ventricle, decreased systolic function, and nonischemic myocardial changes. Contrast-enhanced abdominal computed tomography showed pheochromocytoma, neoplastic lesions, and multiple cysts in the kidneys and pancreas. Genetic analysis revealed a missense mutation of the VHL gene, c.269 A > T (p.Asn90Ile), which was identified as the cause of the disease. Dilated cardiomyopathy and VHL syndrome type 2 were diagnosed. The patient was administered a diuretic, α-blocker, β-blocker, and an angiotensin receptor neprilysin inhibitor (ARNI), but refused pheochromocytoma resection. At the six-month follow-up, the patient was asymptomatic with improved cardiac function., Conclusion: Cardiac involvement is an atypical manifestation in VHL syndrome. Early diagnosis with genetic screening is essential for avoiding life-threatening complications associated with VHL. The management of this rare manifestation of VHL syndrome requires further investigation., (© 2022. The Author(s).)

Purpose of Review: Myocarditis is a disease caused by inflammation of the heart that can progress to dilated cardiomyopathy, heart failure, and eventually death in many patients. Several etiologies are implicated in the development of myocarditis including autoimmune, drug-induced, infectious, and others. All causes lead to inflammation which causes damage to the myocardium followed by remodeling and fibrosis. This review aims to summarize recent findings in biomarkers for myocarditis and highlight the most promising candidates., Recent Findings: Current methods of diagnosing myocarditis, including imaging and endomyocardial biopsy, are invasive, expensive, and often not done early enough to affect progression. Research is being done to find biomarkers of myocarditis that are cost-effective, accurate, and prognostically informative. These biomarkers would allow for earlier screening for myocarditis, as well as earlier treatment, and a better understanding of the disease course for specific patients. Early diagnosis of myocarditis with biomarkers may allow for prompt treatment to improve outcomes in patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Heart transplantation in patients with amyloid cardiomyopathy (ACM) has been historically underused owing to the risk of amyloid recurrence., Methods: Using data from the United Network for Organ Sharing database on patients listed for single-organ heart transplant between 2010 and 2019, we evaluated trend in heart transplant and compared waitlist mortality and graft survival between patients with ACM and dilated cardiomyopathy (DCM). Also, we evaluated for independent predictors of outcomes., Results: Over the study period, 411 adult patients with ACM were added to the heart transplant waitlist. In the propensity-matched cohorts, the rates of waitlist mortality were significantly higher for ACM compared with DCM (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.16-2.65). Over the study period, 330 patients with ACM underwent heart transplant. The number of transplants increased from 22 in 2010 to 59 in 2019 (168% increase). The 5-year graft survival rate was, however, significantly worse for ACM (78%) compared with DCM (82%) (HR,1.46, 1.03-2.08). We identified 2 predictors of graft failure among patients with ACM: namely, renal failure requiring dialysis (HR, 5.4, 1.6-17) and previous history of malignancy (HR, 1.6, 1.0-28). Patients with ACM with neither risk factor had 5-year graft survivals of 82%, which is comparable with DCM (HR, 1.28, 0.90-1.91). On the other hand, patients with ACM and either risk factor had worse 5-year graft survivals of 62% (HR, 2.44, 1.39-4.28)., Conclusions: Increasing numbers of patients with ACM are undergoing heart transplants. Although patients with ACM experience higher waitlist mortality and worse graft survival compared with DCM, selecting carefully screened ACM patients may result in improved outcomes following heart transplant., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Cardiomyopathies are myocardial disorders with a structurally and functionally abnormal heart muscle. In this review, we describe pathophysiological aspects, clinical presentation, diagnosis, risk stratification and therapeutical concepts of the three most common forms of cardiomyopathy: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic cardiomyopathy (ACM).

Emery-Dreifuss muscular dystrophy is a slowly progressive skeletal muscle and joint disorder associated with cardiac complications. Dilated cardiomyopathy was the initial manifestation of Emery-Dreifuss muscular dystrophy in an 8-year-old girl. Despite normal muscle and myocardial biopsies, genetic testing revealed LMNA mutations. As Emery-Dreifuss muscular dystrophy is associated with minimal skeletal muscle weakness, cardiac complications can facilitate its diagnosis.

Fetal dilated cardiomyopathy is a rare anomaly characterized by ventricular dilation and dysfunction. Its causes are diverse, and its outcomes are generally dismal. We describe a rare case of prenatally diagnosed left ventricular apical aneurysm that progressed rapidly to dilated cardiomyopathy. At age 2 months, the infant underwent heart transplantation. Pathologic examination of the explanted heart revealed that the cause of the dilated cardiomyopathy was glycogen storage disease. This case highlights the crucial roles of timely diagnosis, frequent close monitoring, and multidisciplinary care in achieving a successful postnatal outcome., (© 2022 by the Texas Heart® Institute, Houston.)

Objectives: The aim of this study was to review a single institution's experience with EXCOR Paediatric implantation., Methods: Patients <15 years old who underwent EXCOR implantation as a bridge to transplantation between 2015 and 2021 were enrolled. Major adverse events included death, cerebrovascular event resulting in sequelae, major infection (sepsis or surgical site infection requiring open sternal irrigation or device removal) and device malfunction requiring surgical treatment., Results: Overall median age and weight for all 20 children at implantation were 10.8 (interquartile range, 7.9-33.2) months and 6.3 (4.6-10.2) kg. Ten patients (50%) weighed <5 kg. Primary diagnoses were dilated cardiomyopathy in 13 patients, fulminant myocarditis in 3, restrictive cardiomyopathy in 2 and congenital heart disease in 2. Two patients required biventricular assist support. The median support time was 365 (241-636) days. Six patients (30%) were supported for >20 months. One patient died. Seven patients underwent heart transplant. Heart transplant has not been performed in the last 1.5 years. Five patients were weaned from EXCOR support after native myocardial recovery, including a patient with dilated cardiomyopathy who recovered after 24 months of EXCOR support. Major complication-free survival at 6, 12 and 18 months were 79.3%, 49.6% and 38.6%, respectively. Body weight <5 kg at implantation was a risk factor for decreased major complication-free survival., Conclusions: Survival during EXCOR Paediatric support was good, but it prolonged the wait time for a heart transplant. The number of major complications increased over time and was not negligible, especially in small children., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Inflammation is increasingly recognised as a causal factor in the development and progression of cardiovascular disease. With the introduction of immune checkpoint inhibitors in oncology and the ongoing COVID-19 pandemic the role of the immune system in myocardial inflammation (myocarditis) and subsequent inflammatory cardiomyopathy has once again regained attention. In this review, we want to bring myocardial inflammation to the clinician's attention and provide up-to-date knowledge on its diagnostic workup, prognostication, and current management recommendations.

Transient receptor potential vanilloid 2 (TRPV2) channels are expressed and play functional roles in various immune cells. Physical stimuli leading to TRPV2 activation causes mast cell degranulation. Besides their roles in immune cells, it has been shown that TRPV2 channels are pathophysiologically relevant to degenerative muscular diseases such as dilated cardiomyopathy and muscular dystrophy. Hence, development of drug candidates that inhibit human TRPV2 activation is an urgent matter. NK-4, a cryptocyanine dye, inhibited agonist-induced TRPV2 activity in mouse TRPV2-transfected HEK293 cells. However, it remains unclear whether NK-4 exerts regulatory effects on the activation of human TRPV2 channels. In this study, we show that NK-4 inhibits intracellular Ca 2+ increase in human TRPV2-transfected HEK293 cells preactivated with a TRPV2 agonist. The inhibitory effect of NK-4 (IC 50 =0.27 μM) on human TRPV2 activation was 74-fold stronger than that on mouse TRPV2 activation (IC 50 =20 μM). NK-4 also inhibited the agonist-induced TRPV2 expression at the plasma membrane, when the human TRPV2-expressing cells were stimulated with the agonist in the presence of NK-4. These results suggest that NK-4 abrogates the agonist-induced signaling events leading to human TRPV2 activation. Furthermore, TRPV2 agonist caused degranulation of RBL-2H3 cells, which represents a phenomenon related to physical urticarias. NK-4 suppressed the release of β-hexosaminidases upon degradation with IC 50 of 1.9 μM, 35-fold lower than that determined with an anti-allergic drug, Epinastine. Our results suggest that NK-4 would be a potential therapeutic strategy to resolve dilated cardiomyopathy and its associated heart failure as well as physical urticarias.

Non-ischemic dilated cardiomyopathy (NI-DCM) represents a specific etiology of systolic heart failure that usually affect young individuals with a genetic background in up to 40% of cases. Behind the term NI-DCM there is a spectrum of different diseases, and an accurate etiological classification appears pivotal for the clinical management and prognostic stratification of these patients. In the last years the prognosis of NI-DCM patients dramatically improved thanks to the progresses in medical treatment/ device therapy and earlier diagnosis especially in familial context. In this review we summarize the actual state of art in the management of these patients. In the era of precision medicine, a lot of progresses have been made to expand our knowledge on the management of NI-DCM patients. A complex interaction between genotype and external triggers is the main determinant of the clinical phenotype in NI-DCM, and a lot of efforts must be done by clinicians to systematically rule out all the possible causes involved in the pathogenesis. Progresses in cardiac imaging and familial screening led us to detect subtle abnormalities in the initial phase of the disease and also helped us to furtherly stratify the prognosis and arrhythmic risk of these patients. It is plausible that a more precise etiological classification will be needed in the near future. NI-DCM contains a spectrum of different diseases. Proper etiological classification, early diagnosis and strict follow-up are essential to tailor care of these patients.

Background: Systemic juvenile lupus erythematosus can affect any organ including the heart. While pericarditis and endocarditis are the most common cardiac complications, dilated cardiomyopathy remains rare. We report the full recovery of dilated cardiomyopathy in a girl with juvenile lupus., Case Presentation: A 7-year-old girl presented with persistent fever, weight loss, alopecia, positive anti-lupus antibodies, and decreased complement. Examination found dyspnea, tachycardia, and hypotension. Chest X-ray revealed an enlarged cardiac silhouette, and echocardiography showed a left ventricular ejection fraction of 35%. After excluding other causes, systemic lupus erythematosus related dilated cardiomyopathy was selected. Heart failure treatment, Prednisone, and hydroxychloroquine were prescribed. On day three, she developed macrophage activation syndrome which responded to methylprednisolone boluses. Clinical and biological improvement was observed after 4 weeks, normalization of echocardiography after 4 months., Conclusion: A review of the literature confirmed the rare and severe nature of dilated cardiomyopathy in juvenile lupus emphasizing the importance of performing echocardiography at the slightest cardiac sign.

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.)

Oxidative stress, defined as the excess production of reactive oxygen species (ROS) relative to antioxidant defense, plays a significant role in the development of cardiovascular diseases. Endoplasmic reticulum (ER) stress has emerged as an important source of ROS and its modulation could be cardioprotective. Previously, we demonstrated that miR-16-5p is enriched in the plasma of ischemic dilated cardiomyopathy (ICM) patients and promotes ER stress-induced apoptosis in cardiomyocytes in vitro. Here, we hypothesize that miR-16-5p might contribute to oxidative stress through ER stress induction and that targeting miR-16-5p may exert a cardioprotective role in ER stress-mediated cardiac injury. Analysis of oxidative markers in the plasma of ICM patients demonstrates that oxidative stress is associated with ICM. Moreover, we confirm that miR-16-5p overexpression promotes oxidative stress in AC16 cardiomyoblasts. We also find that, in response to tunicamycin-induced ER stress, miR-16-5p suppression decreases apoptosis, inflammation and cardiac damage via activating the ATF6-mediated cytoprotective pathway. Finally, ATF6 is identified as a direct target gene of miR-16-5p by dual-luciferase reporter assays. Our results indicate that miR-16-5p promotes ER stress and oxidative stress in cardiac cells through regulating ATF6, suggesting that the inhibition of miR-16-5p has potential as a therapeutic approach to protect the heart against ER and oxidative stress-induced injury.

Dilated cardiomyopathy (DCM) is a life-threatening form of heart disease that is typically characterized by progressive thinning of the ventricular walls, chamber dilation, and systolic dysfunction. Multiple mutations in the gene encoding filamin C (FLNC), an actin-binding cytoskeletal protein in cardiomyocytes, have been found in patients with DCM. However, the mechanisms that lead to contractile impairment and DCM in patients with FLNC variants are poorly understood. To determine how FLNC regulates systolic force transmission and DCM remodeling, we used an inducible, cardiac-specific FLNC-knockout (icKO) model to produce a rapid onset of DCM in adult mice. Loss of FLNC reduced systolic force development in single cardiomyocytes and isolated papillary muscles but did not affect twitch kinetics or calcium transients. Electron and immunofluorescence microscopy showed significant defects in Z-disk alignment in icKO mice and altered myofilament lattice geometry. Moreover, a loss of FLNC induces a softening myocyte cortex and structural adaptations at the subcellular level that contribute to disrupted longitudinal force production during contraction. Spatially explicit computational models showed that these structural defects could be explained by a loss of inter-myofibril elastic coupling at the Z-disk. Our work identifies FLNC as a key regulator of the multiscale ultrastructure of cardiomyocytes and therefore plays an important role in maintaining systolic mechanotransmission pathways, the dysfunction of which may be key in driving progressive DCM.

Objectives: Myocardial autophagy has been recognized as an important factor in heart failure. It is not known whether changes in ventricular geometry by left ventriculoplasty influence autophagy in ischemic cardiomyopathy. We hypothesized that myocardial autophagy plays an important role in left ventricular (LV) redilation after ventriculoplasty., Methods: Four weeks after ligation of the left anterior descending artery, ventriculoplasty or sham operation was performed. The animals were euthanized at 2 days (early) or 28 days (late) after the second operation. Ventricular autophagy was evaluated by protein expression of microtubule-associated protein light chain 3 II, an autophagosome marker. Cardiomyocyte area was assessed by histologic examination. LV function was evaluated by echocardiography. To examine the implications of autophagy, an autophagy inhibitor (3-methyladenine) was injected intraperitoneally for 3 weeks before sacrifice., Results: The LV was reduced in size early and redilated late after ventriculoplasty. LV systolic function was improved early and later worsened after ventriculoplasty. Light chain 3 II expression decreased early after ventriculoplasty and increased in the late period. Myocyte area increased from the early to late stage after ventriculoplasty. Autophagic inhibition exaggerated the increased myocyte hypertrophy and LV redilation., Conclusions: In a rat model of myocardial infarction, autophagy decreased early after ventriculoplasty and increased again during LV redilation. These results provide new insights into the mechanism underlying the late failure of ventriculoplasty., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)