Dilated Cardiomyopathy Research Articles

The Influence of Arrhythmia on the Outcomes of Pediatric Patients with Idiopathic Dilated Cardiomyopathy.

Children diagnosed with dilated cardiomyopathy (DCM) are at an increased risk of developing arrhythmias, which can significantly affect their overall prognosis. However, the implantation and effectiveness of implantable cardioverter-defibrillators (ICDs) pose challenges in the pediatric population. Therefore, it is crucial to determine the prevalence of arrhythmia-related death in pediatric patients with DCM. This study investigated the correlation between arrhythmias and mortality in pediatric patients with DCM. This retrospective cohort study examined children with idiopathic DCM referred to Rajaie Cardiovascular, Medical, and Research Institute in Tehran, Iran, from 2017 to 2023. All patients underwent a standard 12-lead electrocardiogram, 24-h Holter monitoring, cardiac magnetic resonance imaging, and echocardiography. Patient outcomes, including death, heart transplantation, and survival, were evaluated within one year of Holter monitoring. A total of 178 children (79 males) with a mean age of 83.06 ± 56.41months were included in the study. Overall, 72 deaths (40.4%) and 46 heart transplants (25.8%) were recorded and 60 patients (33.7%) survived. There was no significant association between patients' outcomes with ventricular arrhythmias, late gadolinium enhancement, corrected QT interval, and QRS interval prolongation; however, a significantly higher proportion of dead patients had abnormal heart rate variability (P = 0.034). Heart failure was the leading cause of death, with ventricular arrhythmia accounting for two out of 72 deaths. Both cases of ventricular arrhythmia were associated with severe cardiac dysfunction. Arrhythmia-related mortality is rare in children with idiopathic DCM, with severe heart failure being the primary cause of death in this population. Life-threatening arrhythmias primarily occur in DCM children with more compromised cardiac function.

Integrating metabolomics and proteomics to identify novel drug targets for heart failure and atrial fibrillation

BackgroundAltered metabolism plays a role in the pathophysiology of cardiac diseases, such as atrial fibrillation (AF) and heart failure (HF). We aimed to identify novel plasma metabolites and proteins associating with cardiac disease.MethodsMendelian randomisation (MR) was used to assess the association of 174 metabolites measured in up to 86,507 participants with AF, HF, dilated cardiomyopathy (DCM), and non-ischemic cardiomyopathy (NICM). Subsequently, we sourced data on 1567 plasma proteins and performed cis MR to identify proteins affecting the identified metabolites as well as the cardiac diseases. Proteins were prioritised on cardiac expression and druggability, and mapped to biological pathways.ResultsWe identified 35 metabolites associating with cardiac disease. AF was affected by seventeen metabolites, HF by nineteen, DCM by four, and NCIM by taurine. HF was particularly enriched for phosphatidylcholines (p = 0.029) and DCM for acylcarnitines (p = 0.001). Metabolite involvement with AF was more uniform, spanning for example phosphatidylcholines, amino acids, and acylcarnitines. We identified 38 druggable proteins expressed in cardiac tissue, with a directionally concordant effect on metabolites and cardiac disease. We recapitulated known associations, for example between the drug target of digoxin (AT1B2), taurine and NICM risk. Additionally, we identified numerous novel findings, such as higher RET values associating with phosphatidylcholines and decreasing AF and HF. RET is targeted by drugs such as regorafenib which has known cardiotoxic side-effects. Pathway analysis implicated involvement of GDF15 signalling through RET, and ghrelin regulation of energy homeostasis in cardiac pathogenesis.ConclusionsThis study identified 35 plasma metabolites involved with cardiac diseases and linked these to 38 druggable proteins, providing actionable leads for drug development.

Revived Role of Pulmonary Artery Band in Management of Heart Failure in Pediatric Dilated Cardiomyopathy.

Lack of appropriate durable Ventricular Assist Devices (VADs) that can be managed at home for very young children, and long wait times for transplant have led to search for alternate easily reproducible therapies. In the past decade or more, pulmonary artery banding (PAB), as a new indication of an old technology, has been gradually carried out worldwide as an alternative to mechanical circulatory support in children with end-stage left ventricular dilated cardiomyopathy (DCM) complicated with heart failure(HF), and has achieved encouraging early and mid-term outcomes. Technically, PAB is simple, safe, and effective. This is a promising therapeutic strategy, especially in developing countries where heart transplantation is difficult to implement. As a transition before transplantation, and even a potential treatment, PAB brings more options and hope for children with heart failure who are waiting for transplantation and are refractory to drug therapy. This article reviews the past and current situation, the mechanism, the surgical timing, and application prospect of PAB in the treatment of DCM complicated with heart failure.

Latrophilin-2 Deletion in Cardiomyocyte Disrupts Cell Junction, Leading to D-CMP.

Latrophilin-2 (Lphn2), an adhesive GPCR (G protein-coupled receptor), was found to be a specific marker of cardiac progenitors during the differentiation of pluripotent stem cells into cardiomyocytes or during embryonic heart development in our previous studies. Its role in adult heart physiology, however, remains unclear. The embryonic lethality resulting from Lphn2 deletion necessitates the establishment of cardiomyocyte-specific, tamoxifen-inducible Lphn2 knockout mice, which was achieved by crossing Lphn2flox/flox mice with mice having MerCreMer (tamoxifen-inducible Cre recombinase) under the α-myosin heavy chain promoter. Tamoxifen treatment for several days completely suppressed Lphn2 expression, specifically in the myocardium, and induced the dilated cardiomyopathy (D-CMP) phenotype with serious arrhythmia and sudden death in a short period of time. Transmission electron microscopy showed mitochondrial abnormalities, blurred Z-discs, and dehiscent myofibrils. The D-CMP phenotype, or heart failure, worsened during myocardial infarction. In a mechanistic study of D-CMP, Lphn2 knockout suppressed PGC-1α and mitochondrial dysfunction, leading to the accumulation of reactive oxygen species and the global suppression of junctional molecules, such as N-cadherin (adherens junction), DSC-2 (desmocollin-2; desmosome), and connexin-43 (gap junction), leading to the dehiscence of cardiac myofibers and serious arrhythmia. In an experimental therapeutic trial, activators of p38-MAPK, which is a downstream signaling molecule of Lphn2, remarkably rescued the D-CMP phenotype of Lphn2 knockout in the heart by restoring PGC-1α and mitochondrial function and recovering global junctional proteins. Lphn2 is a critical regulator of heart integrity by controlling mitochondrial functions and cell-to-cell junctions in cardiomyocytes. Its deficiency leads to D-CMP, which can be rescued by activators of the p38-MAPK pathway.

Exploring the predictive values of SERP4 and FRZB in dilated cardiomyopathy based on an integrated analysis

Background and objectiveThe aim of this study was to investigate potential hub genes for dilated cardiomyopathy (DCM).MethodsFive DCM-related microarray datasets were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were used for identification. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, disease ontology, gene ontology annotation and protein-protein interaction (PPI) network analysis were then performed, while a random forest was constructed to explore central genes. Artificial neural networks were used to compare with known genes and to develop new diagnostic models. 240 population blood samples were collected and expression of hub genes was verified in these samples using RT-PCR and demonstrated by Nomogram.ResultsAfter differential analysis, 33 genes were statistically significant (adjusted P < 0.05). Functional enrichment of these differential genes resulted in 85 Gene Ontology (GO) functions identified and 6 pathways enriched for the KEGG pathway. PPI networks and molecular complex assays identified 10 hub genes (adjusted P < 0.05). Random forest identified SMOC2 and SFRP4 as the most important, followed by FCER1G and FRZB. NeuraHF models (SMOC2, SFRP4, FCER1G and FRZB) were selected by artificial neural network model and had better diagnostic efficacy for the onset of DCM, compared with the traditional KG-DCM models (MYH7, ACTC1, TTN and LMNA). Finally, SFRP4 and FRZB were expressed higher in DCM verified by RT-PCR and as a factor for DCM identified by Nomogram.ConclusionsWe performed an integrated analysis and identified SFRP4 and FRZB as a new factor for DCM. But the exact mechanism still needs further experimental verification.

Association Between Coronary Microvascular Dysfunction and Exercise Capacity in Dilated Cardiomyopathy.

Aerobic exercise capacity is an independent predictor of mortality in dilated cardiomyopathy (DCM), but the central mechanisms contributing to exercise intolerance in DCM are unknown. Characterize coronary microvascular function in DCM and determine if cardiovascular magnetic resonance (CMR) measures are associated with aerobic exercise capacity. Prospective case-control comparison of adults with DCM and matched controls. Adenosine-stress perfusion CMR to assess cardiac structure, function and automated inline myocardial blood flow quantification, and cardiopulmonary exercise testing (CPET) to determine peak VO2, were performed. Pre-specified multivariable linear regression, including key clinical and cardiac variables, was undertaken to identify independent associations with peak VO2. Sixty-six patients with DCM (mean age 61 years, 71% male) were propensity-matched to 66 controls (mean age 59 years, 71% male) based on age, sex, body mass index and diabetes. DCM patients had markedly lower peak VO2 (19.8±5.5 versus 25.2±7.3mL/kg/min; P<0.001). The DCM group had greater left ventricular (LV) volumes, lower systolic function, and had more fibrosis compared to controls. In the DCM group, there was similar rest but lower stress myocardial blood flow (1.53±0.49 versus 2.01±0.60mL/g/min; P<0.001) and lower MPR (2.69±0.84 versus 3.15±0.84; P=0.002). Multivariable linear regression demonstrated that LV ejection fraction, extracellular volume fraction and MPR, were independently associated with percentage predicted peak VO2 in DCM (R2=0.531, P<0.001). In comparison to controls, DCM patients have lower stress myocardial blood flow and MPR. In DCM, MPR, LV ejection fraction and fibrosis are independently associated with aerobic exercise capacity.

The emerging role of clonal haematopoiesis in the pathogenesis of dilated cardiomyopathy.

The increased sensitivity of novel DNA sequencing techniques has made it possible to identify somatic mutations in small circulating clones of haematopoietic stem cells. When the mutation affects a 'driver' gene, the mutant clone gains a competitive advantage and has the potential to expand over time, a phenomenon referred to as clonal haematopoiesis (CH), which is emerging as a new risk factor for various non-haematological conditions, most notably cardiovascular disease (e.g. heart failure). Dilated cardiomyopathy (DCM) is a form of non-ischaemic heart failure that is characterized by a heterogeneous aetiology. The first evidence is arising that CH plays an important role in the disease course in patients with DCM, and a strong association of CH with multiple aetiologies of DCM has been described (e.g. inflammation, chemotherapy, and atrial fibrillation). The myocardial inflammation induced by CH may be an important trigger for DCM development for an already susceptible heart, e.g. in the presence of genetic variants, environmental triggers, and comorbidities. Studies investigating the role of CH in the pathogenesis of DCM are expected to increase rapidly. To move the field forward, it will be important to report the methodology and results in a standardized manner, so results can be combined and compared. The accurate measurement of CH in patients with DCM can provide guidance of specific (anti-inflammatory) therapies, as mutations in the CH driver genes prime the inflammasome pathway.

Cardiac genetic counseling services: Exploring downstream revenue in a pediatric medical center.

Genetic counseling is an important component of pediatric cardiac care. The financial costs and benefits of this care have yet to be defined in the literature. Downstream revenue (DSR) analysis can be used to assess the economic impact of genetic counselors (GCs) at their institution beyond the initial patient contact. Previous literature has reported DSR generated by oncology GCs, but there is no published DSR data from a cardiac GC setting. This study measured the DSR generated at a private hospital following a cardiac GC appointment. A chart review identified patients seen by a cardiac GC between 2018 and 2022. The study population included patients and their pediatric relatives who had not previously seen a cardiologist. Patients were included if they were affected with or at-risk for long QT syndrome, hypertrophic cardiomyopathy, dilated cardiomyopathy, or familial thoracic aortic aneurysm at the time of the GC visit. We recorded the frequency of common cardiac services and calculated the reimbursement for all cardiology services for 1 year following the initial GC appointment. The cohort included 121 participants from 61 families. Most individuals were at-risk for (n = 114, 94.3%) rather than affected by an inherited cardiac condition and presented for screening. The total DSR was $247,592.27, with an annual median of $1819.50 per patient (IQR $0, $3761.33). Revenue was similar among individuals who had undergone genetic testing and those who had not. Among participants, 72 (59.5%) had subsequent cardiology services. Most frequently, a patient who presented for subsequent care had an EKG, an echocardiogram, and a cardiology appointment. While the economic contributions of GC services do not speak to the broader value of GC involvement in patient care, they are important metrics for sustainability. This study outlines an approach to evaluating DSR and establishes a baseline understanding of DSR related to cardiac GC services.

Outcomes of HeartMate 3 in pediatric patients with end-stage heart failure: a single-center preliminary experience from Turkey.

We aim to evaluate our initial experience with the HeartMate 3 (HM3) device (Abbott, USA) for palliating pediatric patients with end-stage heart failure (ESHF). We conducted a retrospective review of clinical data from pediatric patients (aged 7-18 years) who underwent HM3 implantation for ESHF at our institution between 2022 and 2024. Patient demographics and follow-up data were comprehensively analyzed. We identified 11 patients (45% males) with a median age of 14 years (IQR 11-17), a median weight of 47 kg (IQR 28-50), a median height of 159 cm (IQR 135-165), and a median body surface area of 1.36 m2 (IQR 1.07-1.53) at the time of the intervention. All patients were diagnosed with dilated cardiomyopathy and categorized with PEDIMACS profiles ranging from one to three. The median ICU stay was 14 days (IQR 6-32), with 11 patients receiving inotropic support for a median of four postoperative days (IQR 3-8). The median follow-up period was 150 days (IQR 90-210). Early complications included two cases of pleural effusion, 1 case of cardiac tamponade, 3 cases of polyuria, and one instance of positive blood cultures. One patient, who was non-compliant with warfarin therapy, developed a thrombus in the right atrium that was resolved with a revision of anticoagulant therapy, and did not experience pump thrombosis. During follow-up, one patient died after 28 days from sepsis, one underwent heart transplantation after 10 days, and nine patients remained alive on the device. Notably, there were no reported cases of pump thrombosis, ischemia, or stroke post- implantation. The HM3 device appears to be a safe and effective palliative option for pediatric patients with ESHF.

ME2 Deficiency Is Associated With Recessive Neurodevelopmental Disorder.

Malate is an important dicarboxylic acid produced from fumarate in the tricarboxylic acid cycle. Deficiencies of fumarate hydrolase (FH) and malate dehydrogenase (MDH), responsible for malate formation and metabolism, respectively, are known to cause recessive forms of neurodevelopmental disorders (NDDs). The malic enzyme isoforms, malic enzyme 1 (ME1) and 2 (ME2), are required for the conversion of malate to pyruvate. To date, there have been no reports linking deficiency of either malic enzyme isoforms to any Mendelian disease in humans. We report a patient presenting with NDD, subtle dysmorphic features, resolved dilated cardiomyopathy, and mild blood lactate elevation. Whole exome sequencing (WES) revealed a homozygous frameshift variant (c.1379_1380delTT, p.Phe460fs*22) in the malic enzyme 2 (ME2) gene resulting in truncated and unstable ME2 protein in vitro. Subsequent deletion of the yeast ortholog of human ME2 (hME2) resulted in growth arrest, which was rescued by overexpression of hME2, strongly supporting an important role of ME2 in mitochondrial function. Our results also support the pathogenicity and candidacy of the ME2 gene and variant in association with NDD. To our knowledge, this is the first report of a Mendelian human disease resulting from a biallelic variant in the ME encoding gene. Future studies are warranted to confirm ME2-associated recessive NDD.

Arrhythmias May Hide a Genetic Cardiomyopathy in Left Ventricular Hypertrabeculation in Children: A Single-Center Experience.

Left ventricular hypertrabeculation (LVHT) is a myocardial disorder with different clinical manifestations, from total absence of symptoms to heart failure, arrhythmias, sudden cardiac death (SCD), and thromboembolic events. It is challenging to distinguish between the benign and pathological forms of LVHT. The aim of this study was to describe the arrhythmic manifestations of LVHT in a large group of pediatric patients and to correlate them with genetic results or other clinical markers. We retrospectively enrolled 140 pediatric patients with diagnosis of LVHT followed at our Institution from 2013 to 2023. Data regarding family history, instrumental exams, cardiac magnetic resonance, genetic testing and outcomes were collected. Most of them had isolated LVHT (80.7%); in other patients, mixed phenotypes (hypertrophic or dilated cardiomyopathy or congenital heart disease) were present. Arrhythmias were found in 33 children (23.6%): 13 (9.3%) supraventricular tachyarrhythmias; 14 (10%) ventricular arrhythmias (five frequent PVCs (premature ventricular contractions), eight patients with ventricular tachycardia (VT), one ventricular fibrillation (VF)); two (1.4%) sinus node disfunctions; two (1.4%) complete atrio-ventricular blocks (AVB), three (2.1%) paroxysmal complete AVB, one (0.7%) severe I degree AVB. Three patients received an ICD (implantable cardioverter defibrillator). Comparison between LVHT patients with (33 pts) and without (107 pts) arrhythmias as regards genetic testing showed a statistical significance for the presence of class 4 or 5 genetic variants and arrhythmic manifestation (p = 0.037). In our pediatric cohort with LVHT, good outcomes were observed, but arrhythmias were not so rare (23.6%); no SCD occurred.

Pathophysiology of dilated cardiomyopathy: from mechanisms to precision medicine.

Dilated cardiomyopathy (DCM) is a complex disease with multiple causes and various pathogenic mechanisms. Despite improvements in the prognosis of patients with DCM in the past decade, this condition remains a leading cause of heart failure and premature death. Conventional treatment for DCM is based on the foundational therapies for heart failure with reduced ejection fraction. However, increasingly, attention is being directed towards individualized treatments and precision medicine. The ability to confirm genetic causality is gradually being complemented by an increased understanding of genotype-phenotype correlations. Non-genetic factors also influence the onset of DCM, and growing evidence links genetic background with concomitant non-genetic triggers or precipitating factors, increasing the extreme complexity of the pathophysiology of DCM. This Review covers the spectrum of pathophysiological mechanisms in DCM, from monogenic causes to the coexistence of genetic abnormalities and triggering environmental factors (the 'two-hit' hypothesis). The roles of common genetic variants in the general population and of gene modifiers in disease onset and progression are also discussed. Finally, areas for future research are highlighted, particularly novel therapies, such as small molecules, RNA and gene therapy, and measures for the prevention of arrhythmic death.

SnRNA-seq reveals differential functional transcriptional pathway alterations in three mutant types of dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a leading cause of heart failure, characterized by ventricular dilation, thinning of the ventricular walls, and systolic dysfunction in either the left or both ventricles, often accompanied by fibrosis. Human cardiac tissue is composed of various cell types, including cardiomyocytes (CMs), fibroblasts (FBs), endothelial cells (ECs), macrophages, lymphocytes and so on. In DCM patients, these cells frequently undergo functional and phenotypic changes, contributing to contractile dysfunction, inflammation, fibrosis, and cell death, thereby increasing the risk of heart failure. This study focuses on DCM patients with mutations (LMNA, RBM20, and TTN) and analyzes functional changes in subpopulations of four cardiac cell types. The study involves functional annotation of subpopulations within each cell type and explores the association between gene mutations and specific functions and pathways. Additionally, the SCENIC method is employed of a particular cell subpopulation with significant functional importance, aiming to identify key transcriptional regulators in specific cell states. By analyzing the expression levels of ligand-receptor pairs in vCM4, vFB2, EC5.0, T cells, and NK cells across the DCM mutant genotypes, we predicted their signaling pathways and communications. This research provides insights into the molecular mechanisms of DCM and potential therapeutic targets.

Comparison of Electrocardiogram between Dilated Cardiomyopathy and Ischemic Cardiomyopathy Based on Empirical Mode Decomposition and Variational Mode Decomposition.

The clinical manifestations of ischemic cardiomyopathy (ICM) bear resemblance to dilated cardiomyopathy (DCM), yet their treatments and prognoses are quite different. Early differentiation between these conditions yields positive outcomes, but the gold standard (coronary angiography) is invasive. The potential use of ECG signals based on variational mode decomposition (VMD) as an alternative remains underexplored. An ECG dataset containing 87 subjects (44 DCM, 43 ICM) is pre-processed for denoising and heartbeat division. Firstly, the ECG signal is processed by empirical mode decomposition (EMD) and VMD. And then, five modes are determined by correlation analysis. Secondly, bispectral analysis is conducted on these modes, extracting corresponding bispectral and nonlinear features. Finally, the features are processed using five machine learning classification models, and a comparative assessment of their classification efficacy is facilitated. The results show that the technique proposed provides a better categorization for DCM and ICM using ECG signals compared to previous approaches, with a highest classification accuracy of 98.30%. Moreover, VMD consistently outperforms EMD under diverse conditions such as different modes, leads, and classifiers. The superiority of VMD on ECG analysis is verified.

Contemporary Management and Prognostic Factors of Arrhythmia Recurrence in Patients with High-Energy Discharge of Cardiac Implantable Electronic Devices.

Background and Objectives: Understanding the underlying causes of implantable cardioverter-defibrillator (ICD) discharges is vital for effective management. This study aimed to evaluate the characteristics of patients admitted following ICD discharge, focusing on myocardial ischemia as a potential exacerbating factor and potential risk factors for VT recurrence. Materials and Methods: This retrospective, single-center study included 81 patients with high energy discharge from cardiac implantable electronic device admitted urgently to the cardiology department from 2015 to 2022. The exclusion criterion was ST-segment elevation acute coronary syndrome. Data were collected anonymously from electronic medical records. Patients were categorized based on coronary angiography, percutaneous angioplasty, presence of significant stenosis, recurrent ventricular tachycardia (VT), and catheter ablation. Clinical variables, including demographic data, echocardiographic parameters, and pharmacotherapy, were analyzed. The primary endpoint was the recurrence of VT during in-hospital stay. Results: Among 81 patients, predominantly male (86.4%), with a mean age of 63.6 years, 55 (67.9%) had coronary artery disease (CAD) as the primary etiology for ICD implantation. Coronary angiography was performed in 34 patients (42.0%) and showed significant stenosis (>50%) in 18 (41.8%) patients, while 8 (26.0%) individuals underwent percutaneous coronary intervention (PCI). Recurrent VT occurred in 21 subjects (26.3%), while ventricular catheter ablation was performed in 36 patients (44.0%). Referral for urgent coronary angiography was associated with presence of diabetes (p = 0.028) and hyperlipidemia (p = 0.022). Logistic regression analysis confirmed NYHA symptomatic class (OR 4.63, p = 0.04) and LVH (OR 10.59, p = 0.049) were independently associated with relapse of VT. CAD patients underwent catheter ablation more frequently (p = 0.001) than those with dilated cardiomyopathy. Conclusions: The study showed a low referral rate for coronary angiography among patients with ICD discharge. Presence of LVH and preexisting symptomatic class influence arrhythmia recurrence. Understanding these associations can guide personalized management strategies for ICD recipients.

Patient selection for left ventricular assist device implantation. The main problems

To analyze the experience of Chazov National Medical Research Center of Cardiology in patient selection for left ventricular assist device (LVAD) implantation. 901 patients, whose documents were sent to Chazov National Medical Research Center of Cardiology from regional medical and prophylactic institutions, were screened as selection for LVAD implantation. Firstly, all patients underwent transthoracic echocardiography performed according to the extended protocol with a comprehensive assessment of the left and right ventricle size and function. Patients who underwent the screening procedure underwent further examination including both laboratory and instrumental diagnostic methods. In addition, the polyclinic database of patients diagnosed with chronic heart failure (CHF) and dilated cardiomyopathy was also analyzed. Among 901 screened patients 7.9% were suitable candidates for LVAD implantation and only 23 (2.6%) patients underwent surgery. Among those not eligible for surgery: 208 (29%) patients were not on optimal medical therapy, 15% of patients had indications for other surgical treatment of CHF, 12% of patients had severe right ventricular failure, 9.8% had severe comorbidities, 6.8% of patients refused surgery. The main problems of selection for LVAD implantation were: low awareness of doctors about the introduction of new treatment methods, poor quality of transthoracic echocardiography, a large percentage of patients not receiving basic therapy for CHF, untimely referral of patients for other types of surgical treatment.

Usefulness of tissue tracking to differentiate tachycardia-induced cardiomyopathy from dilated cardiomyopathy in patients admitted for heart failure.

Differentiation of tachycardia-induced cardiomyopathy (TIC) from dilated cardiomyopathy (DCM) in patients admitted for heart failure (HF) with left ventricular dysfunction and supraventricular tachyarrhythmia (SVT) remains challenging. The role of tissue tracking (TT) in this setting remains unknown. Forty-three consecutive patients admitted for HF due to SVT with left ventricular ejection fraction (LVEF) < 50% undergoing CMR were retrospectively included. Those eventually evolving to LVEF > 50% at follow-up were classified as TIC and those maintaining a LVEF < 50% were classified as DCM. Clinical, echocardiography, and CMR findings, including TT, were analyzed to predict LVEF recovery. Twenty-five (58%) patients were classified as TIC. Late gadolinium enhancement (LGE) was more frequent in DCM group (61% vs 16%, p = 0.004). Left ventricle (LV) peak systolic radial velocity and peak diastolic radial strain rate were lower in DCM group (7.24 ± 4.44mm/s vs 10.8 ± 4.5mm/s; p = 0.015 and -0.12 ± 0.33 1/s vs -0.48 ± 0.51 1/s; p = 0.016, respectively). Right ventricle (RV) peak circumferential displacement was lower in patients with TIC (0.2 ± 1.3 vs 1.3 ± 0.9°; p = 0.009). In the multivariate analysis, diabetes (p = 0.046), presence of LGE (p = 0.028), LV peak systolic radial velocity < 7.5mm/s (p = 0.034), and RV peak circumferential displacement > 0.5° (p = 0.028) were independent predictors of lack of LVEF recovery. In the setting of acute HF with LV dysfunction related to SVT, diabetes, LGE, LV peak systolic velocity, and RV peak circumferential displacement are independent predictors of lack of LVEF recovery and, therefore, represent clinically useful parameters to differentiate TIC from DCM.

Prevalence and prognostic implications of the longitudinal changes of right ventricular systolic function in cardiac magnetic resonance in dilated cardiomyopathy.

Prevalence and prognostic implications of the longitudinal changes of right ventricular systolic function in cardiac magnetic resonance in dilated cardiomyopathy.

Characteristics and prognosis of patients with cardiac sarcoidosis presenting with atrioventricular block and ventricular arrhythmias

Cardiac sarcoidosis (CS) may initially present with life-threatening arrhythmias such as atrioventricular block (AVB) and ventricular arrhythmia (VA), including ventricular tachycardia and ventricular fibrillation. Diagnosing CS is challenging due to subtle or absent findings in routine tests and the low sensitivity of the definitive diagnostic tool, endomyocardial biopsy. CS can also mimic other cardiac conditions such as dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy, and it may occur without any systemic involvement. Consequently, delays in presentation, accurate diagnosis, and initiation of appropriate treatment are frequent. Greater awareness of the condition could improve outcomes for patients with CS. Non-invasive advanced imaging techniques, such as 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance imaging are essential for diagnosis, although they may not be accessible in all clinical settings. Management of arrhythmias in CS involves conventional therapies in the utilization of antiarrhythmics and non-pharmacological therapy (e.g., implantable devices), but with notable divergences in the use of immunosuppression and a preference for implantable cardioverter defibrillators over permanent pacemakers. This narrative review aimed to outline the clinical features of patients with CS presenting with AVB or VA and examine diagnostic investigations, imaging techniques, treatment approaches, and prognosis based on current research and international guidelines.

Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis

Cardiac myosin-specific (MyHC) T cells drive the disease pathogenesis of immune checkpoint inhibitor-associated myocarditis (ICI-myocarditis). To determine whether MyHC T cells are tissue-resident memory T (TRM) cells, we characterized cardiac TRM cells in naive mice and established that they have a distinct phenotypic and transcriptional profile that can be defined by their upregulation of CD69, PD-1, and CXCR6. We then investigated the effects of cardiac injury through a modified experimental autoimmune myocarditis mouse model and an ischemia-reperfusion injury mouse model and determined that cardiac inflammation induces the recruitment of autoreactive MyHC TRM cells, which coexpress PD-1 and CD69. To investigate whether the recruited MyHC TRM cells could increase susceptibility to ICI-myocarditis, we developed a two-hit ICI-myocarditis mouse model where cardiac injury was induced, mice were allowed to recover, and then were treated with anti-PD-1 antibodies. We determined that mice who recover from cardiac injury are more susceptible to ICI-myocarditis development. We found that murine and human TRM cells share a similar location in the heart and aggregate along the perimyocardium. We phenotyped cells obtained from pericardial fluid from patients diagnosed with dilated cardiomyopathy and ischemic cardiomyopathy and established that pericardial T cells are predominantly CD69+ TRM cells that up-regulate PD-1. Finally, we determined that human pericardial macrophages produce IL-15, which supports and maintains pericardial TRM cells.