Dietary linoleic acid supplementation fails to rescue established cardiomyopathy in Barth syndrome.

Barth syndrome (BTHS) is a mitochondrial lipid disorder caused by mutations in TAFAZZIN (TAZ), required for cardiolipin (CL) remodeling. Cardiomyopathy is a major clinical feature, with no curative therapy. Linoleic acid (LA) supplementation is proposed to ameliorate BTHS cardiomyopathy by enhancing linoleoyl group incorporation into CL. While the beneficial effect of dietary LA supplementation in delaying the development of BTHS cardiomyopathy has been recently tested, its potential to reverse established BTHS cardiomyopathy remains unclear. Our study revealed that LA supplementation cannot rescue established BTHS cardiomyopathy in mice, highlighting the importance of early initiation of LA supplementation for maximum benefits.

Clinical Relevance of the Systematic Analysis of Copy Number Variants in the Genetic Study of Cardiomyopathies.

Cardiomyopathies (CMs), one of the main causes of sudden death among the young population, are a heterogeneous group of myocardial diseases, usually with a genetic cause. Next-Generation Sequencing (NGS) has expanded the genes studied for CMs; however, the yield is still around 50%. The systematic study of Copy Number Variants (CNVs) could contribute to improving our diagnostic capacity. These alterations have already been described as responsible for cardiomyopathies in some cases; however, their impact has been rarely assessed. We analyzed the clinical significance of CNVs in cardiomyopathies by studying 11,647 affected patients, many more than those considered in previously published studies. We evaluated the yield of the systematic study of CNVs in a production context using NGS and a novel CNV detection software tool v2.0 that has demonstrated great efficacy, maximizing sensitivity and avoiding false positives. We obtained a CNV analysis yield of 0.8% that fluctuated depending on the type of cardiomyopathy studied (0.29% HCM, 1.41% DCM, 1.88% ARVC, 1.8% LVNC, 1.45% RCM), and we present the frequency of occurrence for 18 genes that agglutinate the 95 pathogenic/likely pathogenic CNVs detected. We conclude the importance of including in diagnostic tests a systematic study of these genetic alterations for the different cardiomyopathies.

Right Ventricular Strain Derived from Cardiac MRI Feature Tracking for the Diagnosis and Prognosis of Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose To demonstrate the myocardial strain characteristics of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), based on revised Task Force Criteria (rTFC), and to explore the prognostic value of strain analysis in ARVC. Materials and Methods This retrospective study included 247 patients (median age, 38 years [IQR, 28-48 years]; 167 male, 80 female) diagnosed with ARVC, based on rTFC, between 2014 and 2018. Patients were divided into "possible" (n =25), "borderline" (n = 40), and "definite" (n = 182) ARVC groups following rTFC. Biventricular global strain parameters were calculated using cardiac MRI feature tracking (FT). The primary outcome was defined as a composite of cardiovascular events, including cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator discharge. Univariable and multivariable cumulative logistic regression and Cox proportional hazards regression analysis were used to evaluate the diagnostic and prognostic value of right ventricle (RV) strain parameters. Results Patients with definite ARVC had significantly reduced RV global strain in all three directions compared with possible or borderline groups (all P < .001). RV global longitudinal strain (GLS) was an independent predictor for disease (odds ratio, 1.09 [95% CI: 1.02, 1.16]; P = .009). During a median follow-up of 3.4 years (IQR, 2.0-4.9 years), 55 patients developed primary end point events. Multivariable analysis showed that RV GLS was independently associated with the occurrence of cardiovascular events (hazard ratio, 1.15 [95% CI: 1.07, 1.24]; P < .001). Kaplan-Meier analysis showed that patients with RV GLS worse than median had a higher risk of combined cardiovascular events (log-rank P < .001). Conclusion RV GLS derived from cardiac MRI FT demonstrated good diagnostic and prognostic value in ARVC. Keywords: MR Imaging, Image Postprocessing, Cardiac, Right Ventricle, Cardiomyopathies, Arrhythmogenic Right Ventricular Cardiomyopathy, Revised Task Force Criteria, Cardiovascular MR, Feature Tracking, Cardiovascular Events Supplemental material is available for this article. © RSNA, 2024.

Variation of computed tomography-derived extracellular volume fraction and the impact of protocol parameters: A systematic review and meta-analysis.

BACKGROUND: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation. METHODS: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity. RESULTS: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I2 â€‹= â€‹93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates. CONCLUSION: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis.

Anthracycline-Induced Cardiomyopathy in Cancer Survivors: Management and Long-Term Implications.

Recent advancements in personalized treatments, such as anthracycline chemotherapy, coupled with timely diagnoses, have contributed to a decrease in cancer-specific mortality rates and an improvement in cancer prognosis. Anthracyclines, a potent class of antibiotics, are extensively used as anticancer medications to treat a broad spectrum of tumors. Despite these advancements, a considerable number of cancer survivors face increased risks of treatment complications, particularly the cardiotoxic effects of chemotherapeutic drugs like anthracyclines. These effects can range from subclinical manifestations to severe consequences such as irreversible heart failure and death, highlighting the need for effective management of chemotherapy side effects for improved cancer care outcomes. Given the lack of specific treatments, early detection of subclinical cardiac events post-anthracycline therapy and the implementation of preventive strategies are vital. An interdisciplinary approach involving cardiovascular teams is crucial for the prevention and efficient management of anthracycline-induced cardiotoxicity. Various factors, such as age, gender, duration of treatment, and comorbidities, should be considered significant risk factors for developing chemotherapy-related cardiotoxicity. Tools such as electrocardiography, echocardiography, nuclear imaging, magnetic resonance imaging, histopathologic evaluations, and serum biomarkers should be appropriately used for the early detection of anthracycline-related cardiotoxicity. Furthermore, understanding the underlying biological mechanisms is key to developing preventive measures and personalized treatment strategies to mitigate anthracycline-induced cardiotoxicity. Exploring specific cardiotoxic mechanisms and identifying genetic variations can offer fresh perspectives on innovative, personalized treatments. This chapter aims to discuss cardiomyopathy following anthracycline therapy, with a focus on molecular mechanisms, preventive strategies, and emerging treatments.

Dilatative fetal cardiomyopathy followed by a mirror syndrome.

Mirror syndrome (Ballantyne syndrome) is a rare condition characterized by maternal edema, which often affects the lungs. It mirrors the image of fetal and placental edema; therefore, it is also called triple edema. We present the case of a 37-year-old secundigravida, referred to our clinic at 26 weeks of a pregnancy complicated by fetal dilatative restrictive cardiomyopathy and hydrops, placentomegaly, new-onset dyspnea, and maternal calf edema. Due to worsening mirror syndrome, preterm labor was induced. Labor was complicated, with soft tissue dystocia, stillbirth, and postpartum hemorrhage. The first pregnancy was also complicated by fetal right ventricular noncompaction dilatative cardiomyopathy. A eutrophic male child was born vaginally at term and died due to deterioration of the cardiac disease in the third year of life. Next-generation sequencing panel for pediatric cardiology was performed in the deceased child and parents. Two gene variants were recorded: MYOM1: c.770_771delCA (p.Thr257fs) and TPM1: c.814G>A (p.Glu272Lys). Both variants were classified as variants of uncertain significance. This case emphasizes the importance of antenatal counseling, the timing of labor induction, appropriate management of possible complications such as postpartum hemorrhage and soft tissue dystocia, and the interpretation of placental biomarkers in the context of mirror syndrome. Finally, it contributes to understanding the clinical significance of the MYOM1 and TPM1 gene variants.

Differential Deep RNA Sequencing for Diagnostic Detection of Microbial Infections in Inflammatory Cardiomyopathy.

BACKGROUND: Inflammatory heart disease can be triggered by a variety of causes, both infectious and noninfectious in nature. We hypothesized that inflammatory cardiomyopathy is potentially related to microbial infection. METHODS: In this retrospective study, we used deep RNA sequencing on formalin-fixed paraffin-embedded heart tissue specimens to detect pathogenic agents. We first investigated 4 single-sample cases to test the feasibility of this diagnostic protocol and further 3 control-sample paired cases to improve the protocol with differential metatranscriptomics next-generation sequencing (mtNGS) analysis. RESULTS: We demonstrate that differential mtNGS allows identification of various microbials as potentially pathogenic, for example, Cutibacterium acnes, Corynebacterium aurimucosum, and Pseudomonas denitrificans, which are usually commensal in healthy individuals. Differential mtNGS also allows characterization of human host response in each individual by profiling alterations of gene expression, networked pathways, and inferred immune cell compositions, information of which is beneficial for us to understand different etiologies and immunity roles in each case. Additionally, differential mtNGS allows the identification of genetic variants in patients that may contribute to their susceptibility to particular microbial infections. CONCLUSIONS: The demonstrated power of differential mtNGS in simultaneous capture of both the infectious microbial(s) and the status of human host immune response could help us better understand the pathogenesis of complex inflammatory cardiomyopathy, if conducted on a larger scale of the population. The developed differential mtNGS method could also shed light on its translation and adoption of such a laboratory test in clinic practice, allowing for a more effective diagnosis to guide therapeutic treatment of the disease.

Integrating Clinical Phenotype With Multiomics Analyses of Human Cardiac Tissue Unveils Divergent Metabolic Remodeling in Genotype-Positive and Genotype-Negative Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is caused by sarcomere gene mutations (genotype-positive HCM) in ≈50% of patients and occurs in the absence of mutations (genotype-negative HCM) in the other half of patients. We explored how alterations in the metabolomic and lipidomic landscape are involved in cardiac remodeling in both patient groups. METHODS: We performed proteomics, metabolomics, and lipidomics on myectomy samples (genotype-positive N=19; genotype-negative N=22; and genotype unknown N=6) from clinically well-phenotyped patients with HCM and on cardiac tissue samples from sex- and age-matched and body mass index-matched nonfailing donors (N=20). These data sets were integrated to comprehensively map changes in lipid-handling and energy metabolism pathways. By linking metabolomic and lipidomic data to variability in clinical data, we explored patient group-specific associations between cardiac and metabolic remodeling. RESULTS: HCM myectomy samples exhibited (1) increased glucose and glycogen metabolism, (2) downregulation of fatty acid oxidation, and (3) reduced ceramide formation and lipid storage. In genotype-negative patients, septal hypertrophy and diastolic dysfunction correlated with lowering of acylcarnitines, redox metabolites, amino acids, pentose phosphate pathway intermediates, purines, and pyrimidines. In contrast, redox metabolites, amino acids, pentose phosphate pathway intermediates, purines, and pyrimidines were positively associated with septal hypertrophy and diastolic impairment in genotype-positive patients. CONCLUSIONS: We provide novel insights into both general and genotype-specific metabolic changes in HCM. Distinct metabolic alterations underlie cardiac disease progression in genotype-negative and genotype-positive patients with HCM.

Abnormal conduction-induced cardiomyopathy: a poorly explored entity.

A dyssynchronous biventricular activation, which can be determined by left bundle branch block, chronic right ventricular pacing, frequent premature ventricular complexes, or pre-excitation, can cause a global abnormal contractility, thus leading to systolic dysfunction and left ventricular remodelling in a unique nosological entities: abnormal conduction-induced cardiomyopathies. In this clinical scenario, the mainstay therapy is eliminating or improving LV dyssynchrony, removing the trigger. This usually ensures the improvement and even recovery of cardiac geometry and left ventricular function, especially in the absence of genetic background. A multidisciplinary approach, integrating advanced multimodal imaging, is essential for the systematic aetiological definition and the subsequent evaluation and aetiology-guided therapies of patients and their families. This review aims to describe mechanisms, prevalence, risk factors, and diagnostic and therapeutic approach to the various abnormal conduction-induced cardiomyopathies, starting from reasonable certainties and then analysing the grey areas requiring further studies.

Navigating the penetrance and phenotypic spectrum of inherited cardiomyopathies.

Inherited cardiomyopathies are genetic diseases that can lead to heart failure and sudden cardiac death. These conditions tend to run in families, following an autosomal dominant pattern where first-degree relatives have a 50% chance of carrying the pathogenic variant. Despite significant advancements and increased accessibility of genetic testing, accurately predicting the phenotypic expression of these conditions remains challenging due to the inherent variability in their clinical manifestations and the incomplete penetrance observed. This poses challenges in providing patient care and effectively communicating the potential risk of future disease to patients and their families. To address these challenges, this review aims to synthesize the available evidence on penetrance, expressivity, and factors influencing disease expression to improve communication and risk assessment for patients with inherited cardiomyopathies and their family members.

Outcomes after septal myectomy in a cohort of patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) with left ventricular outflow tract obstruction that doesn't improve with pharmacological management often requires septal myectomy. However, there are few centers with experience in the practice of this procedure in our country. We describe the clinical and echocardiographic characteristics and postoperative outcomes of patients with HCM indicated for septal myectomy at a reference center in Colombia. MATERIALS AND METHODS: Retrospective cohort study. Patients undergoing septal myectomy between 2010 and 2023 were included. Data were collected before and two years after surgery. RESULTS: 18 patients were included. The mean age was 50 years. The predominant functional class was NYHA II/III (94 %). Asymmetric septal variant (83.3 %) was the most frequent as well as obstructive phenotype (88.8 %). After myectomy, 70.5 % improved to NYHA I and 62.4 % had no significant gradient (<30 mmHg), and the most of patient improved SAM. One patient died post-procedure, anymore complications were presented. DISCUSSION/CONCLUSIONS: Septal myectomy is a safe procedure, with clinical and echocardiographic improvement, with low complication rates.

Waitlist Outcomes for Pediatric Heart Transplantation in the Current Era: An Analysis of the Pediatric Heart Transplant Society Database.

BACKGROUND: Waitlist mortality (WM) remains elevated in pediatric heart transplantation. Allocation policy is a potential tool to help improve WM. This study aims to identify patients at highest risk for WM to potentially inform future allocation policy changes. METHODS: The Pediatric Heart Transplant Society database was queried for patients <18 years of age indicated for heart transplantation between January 1, 2010 to December 31, 2021. Waitlist mortality was defined as death while awaiting transplant or removal from the waitlist due to clinical deterioration. Because WM is low after the first year, analysis was limited to the first 12 months on the heart transplant list. Kaplan-Meier analysis and log-rank testing was conducted to compare unadjusted survival between groups. Cox proportional hazard models were created to determine risk factors for WM. Subgroup analysis was performed for status 1A patients based on body surface area (BSA) at time of listing, cardiac diagnosis, and presence of mechanical circulatory support. RESULTS: In total 5974 children met study criteria of which 3928 were status 1A, 1012 were status 1B, 963 were listed status 2, and 65 were listed status 7. Because of the significant burden of WM experienced by 1A patients, further analysis was performed in only patients indicated as 1A. Within that group of patients, those with smaller size and lower eGFR had higher WM, whereas those patients without congenital heart disease or support from a ventricular assist device (VAD) at time of listing had decreased WM. In the smallest size cohort, cardiac diagnoses other than dilated cardiomyopathy were risk factors for WM. Previous cardiac surgery was a risk factor in the 0.3 to 0.7 m2 and >0.7 m2 BSA groups. VAD support was associated with lower WM other than in the single ventricle cohort, where VAD was associated with higher WM. Extracorporeal membrane oxygenation and mechanical ventilation were associated with increased risk of WM in all cohorts. CONCLUSIONS: There is significant variability in WM among status-1A patients. Potential refinements to current allocation system should factor in the increased WM risk we identified in patients supported by extracorporeal membrane oxygenation or mechanical ventilation, single ventricle congenital heart disease on VAD support and small children with congenital heart disease, restrictive cardiomyopathy, or hypertrophic cardiomyopathy.

The Role of Magnetic Resonance Imaging in Cardiomyopathies in the Light of New Guidelines: A Focus on Tissue Mapping.

Cardiomyopathies (CMPs) are a group of myocardial disorders that are characterized by structural and functional abnormalities of the heart muscle. These abnormalities occur in the absence of coronary artery disease (CAD), hypertension, valvular disease, and congenital heart disease. CMPs are an increasingly important topic in the field of cardiovascular diseases due to the complexity of their diagnosis and management. In 2023, the ESC guidelines on cardiomyopathies were first published, marking significant progress in the field. The growth of techniques such as cardiac magnetic resonance imaging (CMR) and genetics has been fueled by the development of multimodal imaging approaches. For the diagnosis of CMPs, a multimodal imaging approach, including CMR, is recommended. CMR has become the standard for non-invasive analysis of cardiac morphology and myocardial function. This document provides an overview of the role of CMR in CMPs, with a focus on tissue mapping. CMR enables the characterization of myocardial tissues and the assessment of cardiac functions. CMR sequences and techniques, such as late gadolinium enhancement (LGE) and parametric mapping, provide detailed information on tissue composition, fibrosis, edema, and myocardial perfusion. These techniques offer valuable insights for early diagnosis, prognostic evaluation, and therapeutic guidance of CMPs. The use of quantitative CMR markers enables personalized treatment plans, improving overall patient outcomes. This review aims to serve as a guide for the use of these new tools in clinical practice.

Coronary Angiography in Patients With Left Ventricular Hypertrabeculation/Noncompaction.

BACKGROUND: Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown pathogenesis, frequently associated with neuromuscular disorders. The relevance of coronary artery disease (CAD) in LVHT is largely unknown. This study aimed to assess the role of CAD as a prognostic marker in LVHT. METHODS: Data from patients with LVHT were collected from an echocardiographic laboratory. The hospital information system was retrospectively screened for coronary angiography. The association of CAD with clinical, echocardiographic, and neurologic baseline parameters was assessed. End points were all-cause death and heart transplantation. RESULTS: A total of 154 patients (mean [SD] age, 57 [13.7] years; 31% female) who had undergone coronary angiography between 1995 and 2020 were included in the study. Coronary angiography disclosed CAD in 53 of 154 patients. Patients with CAD were older (mean [SD] age of, 64.2 [12.9] years vs 52.7 [12.4] years; P < .001); more frequently had angina pectoris (P = .05), diabetes (P = .002), and hypertension (P = .03); and more frequently had 3 or more electrocardiographic abnormalities (P = .04) than patients without CAD. During a median (IQR) follow-up period of 6.48 (2.44-11.20) years, 39% of patients reached an end point (death, n = 56; heart transplantation, n = 4). Mortality was 4.5% per year, and the rate of death or heart transplantation did not differ between patients with and without CAD (P = .26). Patients with 3-vessel disease had a worse prognosis than patients with 1- or 2-vessel disease (P = .046). CONCLUSION: In patients with LVHT, CAD does not appear to be associated with an increased rate of death or heart transplantation.

[Pheochromocytoma as a simulator of cardiac pathology]. / Feocromocitoma como simulador de patología cardiaca.

Pheochromocytomas are rare neuroendocrine tumors that can present as hypertensive crises or serious cardiac and cerebrovascular complications that endanger the patient's life. Two unusual cases of adrenergic crises induced by pheochromocytoma with cardiovascular manifestations are presented, one with multiple complications/multiorgan failure, fatal outcome and definitive diagnosis in the post mortem autopsy, and another with a satisfactory evolution after diagnosis and appropriate treatment.

HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology.

Cardiac abnormalities were identified early in the epidemic of AIDS, predating the isolation and characterization of the etiologic agent, HIV. Several decades later, the causation and pathogenesis of cardiovascular disease (CVD) linked to HIV infection continue to be the focus of intense speculation. Before the widespread use of antiretroviral therapy, HIV-associated CVD was primarily characterized by HIV-associated cardiomyopathy linked to profound immunodeficiency. With increasing antiretroviral therapy use, viral load suppression, and establishment of immune competency, the effects of HIV on the cardiovascular system are more subtle. Yet, people living with HIV still face an increased incidence of cardiovascular pathology. Advances in cardiac imaging modalities and immunology have deepened our understanding of the pathogenesis of HIV-associated CVD. This review provides an overview of the pathogenesis of HIV-associated CVD integrating data from imaging and immunologic studies with particular relevance to the HIV population originating from high-endemic regions, such as sub-Saharan Africa. The review highlights key evidence gaps in the field and suggests future directions for research to better understand the complex HIV-CVD interactions.

Transient Left Ventricular Dysfunction from Cardiomyopathies to Myocardial Viability: When and Why Cardiac Function Recovers.

Transient left ventricular dysfunction (TLVD), a temporary condition marked by reversible impairment of ventricular function, remains an underdiagnosed yet significant contributor to morbidity and mortality in clinical practice. Unlike the well-explored atherosclerotic disease of the epicardial coronary arteries, the diverse etiologies of TLVD require greater attention for proper diagnosis and management. The spectrum of disorders associated with TLVD includes stress-induced cardiomyopathy, central nervous system injuries, histaminergic syndromes, various inflammatory diseases, pregnancy-related conditions, and genetically determined syndromes. Furthermore, myocardial infarction with non-obstructive coronary arteries (MINOCA) origins such as coronary artery spasm, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD) may also manifest as TLVD, eventually showing recovery. This review highlights the range of ischemic and non-ischemic clinical situations that lead to TLVD, gathering conditions like Tako-Tsubo Syndrome (TTS), Kounis syndrome (KS), Myocarditis, Peripartum Cardiomyopathy (PPCM), and Tachycardia-induced cardiomyopathy (TIC). Differentiation amongst these causes is crucial, as they involve distinct clinical, instrumental, and genetic predictors that bode different outcomes and recovery potential for left ventricular function. The purpose of this review is to improve everyday clinical approaches to treating these diseases by providing an extensive survey of conditions linked with TLVD and the elements impacting prognosis and outcomes.

Cardiovascular Magnetic Resonance Imaging in Myocardial Disease.

Cardiovascular magnetic resonance (CMR) is the central non-invasive imaging investigation for the evaluation of myocardial disease. It is the well-established gold standard for measuring cardiac chamber volumes, systolic function, and left ventricular mass, and it brings unique information for therapeutic decisions. In addition, its tissue characterization capability, through T1, T2, and T2* mapping, as well as early and late gadolinium enhancement (LGE) sequences, allows to differentiate in many cases among ischemic, inflammatory, and infiltrative heart disease and permits the quantification of myocardial fibrosis, providing valuable diagnostic and prognostic information. This review aims to highlight the main CMR features of different cardiomyopathies.