Löffler endocarditis, an idiopathic hypereosinophilic syndrome, can present symptoms of heart failure and peripheral eosinophilia. We present the case of a 46-year-old woman with fatigue, shortness of breath, and edema, who was found to have thrombocytopenia, elevated cardiac biomarkers, and hypereosinophilia (2.96 k/uL). Cardiac MRI revealed hypertrophic cardiomyopathy, right ventricular hypertrophy, and a restrictive filling pattern, raising suspicion for Löffler endocarditis. Despite initial corticosteroid and diuretic treatment, she was readmitted with persistent symptoms. This case highlights the diagnostic imaging and treatment challenges with corticosteroid therapy, to control eosinophilic infiltration and prevent irreversible cardiac damage. Löffler endocarditis should be considered in the imaging differential diagnosis of unexplained heart failure.

Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized infiltrative cardiomyopathy characterized by progressive myocardial amyloid deposition, leading to heart failure, arrhythmias, and conduction abnormalities. Recent studies suggest that ATTR-CM is not uncommon among older patients hospitalized with heart failure with preserved ejection fraction and left ventricular hypertrophy, highlighting that the disease remains substantially underdiagnosed. Conduction disturbances are common during the course of the disease, and advanced atrioventricular conduction disease may require permanent pacemaker implantation; however, complete heart block as the initial presentation remains uncommon. We report the case of a 70-year-old woman who presented with exertional syncope and was found to have complete atrioventricular block with a wide-QRS escape rhythm, requiring emergency temporary pacing followed by permanent dual-chamber pacemaker implantation. Transthoracic echocardiography demonstrated marked biventricular hypertrophy, biatrial enlargement, restrictive left ventricular filling pattern, and severely impaired global longitudinal strain with a characteristic apical sparing pattern, raising a strong suspicion of cardiac amyloidosis. Cardiac MRI revealed diffuse biventricular subendocardial late gadolinium enhancement and abnormal myocardial nulling, highly suggestive of amyloid infiltration. Hematological investigations excluded light-chain amyloidosis, and technetium-99m hydroxymethylene diphosphonate scintigraphy demonstrated Perugini grade 3 myocardial uptake, establishing the non-biopsy diagnosis of ATTR-CM. Tafamidis therapy was subsequently initiated. This case highlights complete heart block as an uncommon initial presentation of ATTR-CM. It underscores the pivotal role of multimodality imaging in achieving an early and accurate diagnosis, thereby enabling timely initiation of disease-modifying therapy.

Pediatric cardiomyopathies (CM) are rare and heterogeneous heart disorders, including hypertrophic, dilated, restrictive, arrhythmogenic, and non-dilated CM. While their genetic basis is well characterized in adults, it remains less clearly defined in children particularly in early-onset apparently isolated and syndromic forms. We conducted a retrospective study (2018-2024) of 59 pediatric patients who underwent Whole-Exome Sequencing (WES) for CM at Amiens and Lille University Hospitals, aiming to characterize the genetic architecture of pediatric CM. WES identified at least one Variant Of Interest (VOI) in 62.7% of patients (37/59), including 45.8% (27/59) of P/LP variants, and 16.9% (10/59) of VUS. VOI identification yields for HCM and DCM were respectively 67.7% and 57.1%. Yield was higher in patients diagnosed before 1 year of age compared with those diagnosed later (72.7% vs. 56.7%). Variants were identified in classical CM genes, including sarcomeric genes, but also in less typical and syndromic genes. Among patients diagnosed before 6 months, 55% carried a variant in genes associated with syndromic cardiomyopathy, including cases with initially isolated cardiac phenotypes. These findings support the use of WES as a first-line approach in pediatric CM and highlight the contribution of complex and syndromic genetic architectures to early-onset and severe diseases.

Restrictive cardiomyopathy (RCM) is characterized by pronounced cardiac fibrosis (CF), leading to ventricular stiffening and diastolic dysfunction. While cardiomyocyte (CM) mutations are known triggers, the mechanisms initiating profibrotic signaling remain elusive. This study investigates the role of CM-derived exosomes and specific transfer RNA-derived small RNAs (tsRNAs) in this pathogenic intercellular communication. Using a cTnIR193H knock-in mouse model, we observed pronounced CF prior to the onset of heart failure, without significant CM apoptosis. This primary fibrotic response was mediated by a paracrine mechanism, as conditioned medium from mutant CMs was sufficient to activate fibroblasts. Subsequent small RNA sequencing of CM-derived exosomes identified the tRNA-derived fragment 5'tiRNA-GluCTC as a significantly enriched species. Functional studies established this RNA as a critical mediator, demonstrating that its overexpression exacerbated fibrotic responses in vitro and induced fibrotic remodeling in wild-type mice, while its inhibition via a cardiac-targeted Adeno-associated virus sponge attenuated fibroblast activation and alleviated fibrosis in RCM mice. Mechanistically, 5'tiRNA-GluCTC is transferred to fibroblasts, directly targets the 3'UTR of Foxq1 to repress its expression, and consequently activates the Smad3/p-Smad3 signaling cascade. Collectively, these results delineate a 5'tiRNA-GluCTC/Foxq1/Smad3 signaling axis that drives fibrosis in RCM, uncovering a previously uncharacterized signaling cascade with therapeutic potential.

Left ventricular non-compaction (LVNC) is a genetically heterogeneous cardiomyopathy linked to sarcomeric and cytoskeletal genes, yet only one case has previously been associated with a troponin I (TNNI3) variant. Our case report describes the exceptionally rare coexistence of LVNC, a novel TNNI3 variant, and a hypermobile Ehlers-Danlos syndrome (hEDS) phenotype, genetically unrelated to TNNI3, resulting in a distinct clinical presentation.

Atrial fibrillation (AF) is common in transthyretin amyloid cardiomyopathy (ATTR-CM), affecting over 70% of patients and often preceding cardiomyopathy diagnosis. Amyloid infiltration promotes structural, mechanical, and electrical atrial remodeling, creating an arrhythmogenic substrate and increasing thromboembolic risk that may be independent of Congestive heart failure, Hypertension, Age, Diabetes, Stroke, Vascular disease, Age, and Sex category score, supporting a low threshold for anticoagulation. AF management in ATTR-CM is challenging because restrictive physiology, autonomic dysfunction, and conduction disease limit conventional rate-control strategies. Rhythm control may be advantageous, especially when initiated early. Antiarrhythmic therapy and direct-current cardioversion remain common first-line approaches, although recurrence is frequent. Catheter ablation is an emerging option for selected patients, with observational data suggesting better arrhythmia control, symptom improvement, and fewer hospitalizations, particularly in earlier-stage disease. As disease-modifying therapies, including tafamidis, acoramidis, and vutrisiran, improve survival, optimizing atrial arrhythmia management is increasingly important. This review summarizes mechanisms, prognosis, and contemporary AF management in ATTR-CM, with emphasis on early rhythm control and ablation.

Background: Transthyretin amyloidosis (ATTR) is a progressive disease that causes a restrictive cardiomyopathy. Vutrisiran, a subcutaneous RNA interference (RNAi) therapy, is an approved treatment. This systematic review and meta-analysis evaluates its efficacy and safety with respect to transthyretin (TTR) reduction, functional capacity, quality of life, mortality, and adverse events. Methods: We identified 1,032 records, of which three randomized controlled trials-HELIOS-A, HELIOS-B, and a Phase 1 study-comprising 976 participants (508 vutrisiran; 468 comparator) met the inclusion criteria. Comparator participants received placebo, patisiran (an active reference comparator in HELIOS-A), or external placebo from the APOLLO trial. Outcomes assessed were TTR reduction, functional capacity, quality of life, mortality, and adverse events, pooled using random-effects models reporting mean differences and risk ratios. Results: Vutrisiran achieved a rapid, durable TTR reduction of up to 97% in healthy volunteers at the highest dose, and a sustained steady-state reduction in the HELIOS-A and HELIOS-B trials. QoL outcomes showed a protective effect of vutrisiran, with slowed deterioration in the intervention group. Functional outcomes (10-MWT, 6-MWT) suggested slower decline in mobility and functional capacity. Mortality showed a non-significant reduction (RR 0.51; p = 0.29; I[2] = 62%), with most deaths considered unrelated to treatment. The safety analysis showed fewer falls (RR 0.62; p = 0.001; I[2] = 0%) but no significant difference in overall adverse events (AEs) (RR 1.01; p = 0.76) or serious AEs (RR 0.82; p = 0.23). A sensitivity analysis supported the adverse-event findings. Conclusions: Vutrisiran consistently suppressed TTR and showed signals of benefit in quality of life, function, and mortality, though most of these outcomes did not reach statistical significance. It reduced fall risk without increasing adverse events, indicating a favourable safety profile. Larger, long-term RCTs are needed to confirm survival and functional benefits.

Myopalladin (MYPN) is a Z-disc protein involved in sarcomere integrity and nuclear signaling, and pathogenic variants have increasingly been recognized as causes of inherited cardiomyopathy associated with arrhythmias and progressive heart failure. We report a 48-year-old African American woman with MYPN-associated nonischemic cardiomyopathy (ejection fraction <15%), atrial fibrillation, left ventricular thrombus, prior bilateral strokes, and ICD placement who presented with acute ischemic stroke after missing anticoagulation therapy. She underwent mechanical thrombectomy for a left M1 occlusion with subsequent re-occlusion. Her hospital course was complicated by recurrent polymorphic ventricular tachycardia requiring ICD shocks, refractory heart failure requiring inotropic support, acute kidney injury, sepsis, and multi-organ dysfunction despite maximal guideline-directed therapy. MYPN mutations disrupt both sarcomere structural stability and stress-response signaling, contributing to ventricular dysfunction and arrhythmogenesis. Similar to other inherited cardiomyopathies involving sarcomeric and cytoskeletal genes, MYPN-associated disease may progress rapidly despite conventional therapy. This case highlights the severe clinical course and systemic complications of MYPN-associated cardiomyopathy and underscores the importance of early genetic testing, family screening, and timely referral for advanced heart failure therapies.