Genetic Characterization of Dilated Cardiomyopathy in Romanian Adult Patients.

Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of <35% was observed in 41.9% of patients with disease-causing variants and 55% with negative or uncertain findings. Further genotype-phenotype correlations were explored in this study population. The substantial percentage (50.8%) of disease-causing variants identified in patients with DCM acknowledges the importance of genetic investigations. This study highlights the genetic landscape in genes associated with DCM in the Romanian population.

Exercise test is essential in LV-only fusion CRT pacing without right ventricle lead.

Purpose: Left ventricle (LV)-only pacing is non-inferior to biventricular pacing but permanent fusion pacing is needed to ensure cardiac resynchronization therapy (CRT) responsiveness. The role of systematic exercise testing (ET) in these patients has not been established. This study was designed to assess clinical and therapeutic implications (device programming/drugs) of systematic ET in patients requiring fusion-pacing CRT without an right ventricle (RV) lead. Methods: Consecutive patients with a right atrium/LV-only dual-chamber (DDD) pacing system were included. Prospective data were obtained: device interrogation, ET, and echocardiography at every 6-month follow-up visit. CRT assessment during ET included maximal heart rate, beat-to-beat echocardiography analysis of LV fusion pacing, LV loss of capture, and improvement in exercise capacity. If LV loss of capture or unsatisfactory LV fusion pacing occurred, reprogramming was individualized for each patient and ET redone. Results: A total of 55 patients (29 male) aged 62±11 years were included. During follow-up (39±18 months), a total of 235 ETs were performed, with mean exercise load 6.4±1.3 metabolic equivalents of task (118±35 W, maximal heart rate 119±17 beats/min). Twenty patients (36%) had inadequate pacing or loss of LV capture during ET, due to exceeding the maximum tracking rate (11%), chronotropic incompetence (7%), and LV pacing outside the fusion-pacing band (18%), caused by physiological shortening of the PR interval or exagerated LV preexcitation during maximum exercise. Post-ET CRT-device optimization included reprogramming of rate-adaptive atrioventricular interval (total decrease 23±8 ms), individualized programming of maximum tracking rate, or rate-response function. Drug optimization was performed in 32% of patients, and ET redone in 36%. Conclusion: In one of three ETs, an intervention in device and medication optimization was done to ensure a better outcome. Routine ET should be a standard approach to maximize fusion-pacing CRT response during follow-up.