Background: The aim of this study was to explore the rare variants in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM). Methods: Forty-five unrelated probands with HCM were screened by targeted next generation sequencing (NGS) of 47 core and emerging genes connected with HCM. Results: We identified 95 variants with allele frequency < 0.1% in population databases. MYBPC3 and TTN had the largest number of rare variants (17 variants each). A definite genetic etiology was found in 6 probands (13.3%), while inconclusive results due to either known or novel variants were established in 31 cases (68.9%). All disease-causing variants were detected in sarcomeric genes (MYBPC3 and MYH7 with two cases each, and one case in TNNI3 and TPM1 respectively). Multiple variants were detected in 27 subjects (60%), but no proband carried more than one causal variant. Of note, almost half of the rare variants were novel. Conclusions: Herein we reported for the first time the rare variants identified in core and putative genes associated with HCM in a cohort of Romanian unrelated adult patients. The clinical significance of most detected variants is yet to be established, additional studies based on segregation analysis being required for definite classification.

Background Right ventricular – arterial (RV‐PA) coupling can be estimated by echocardiography using the ratio between (TAPSE) and pulmonary arterial systolic pressure (PASP). TAPSE/PASP ratio proved to be a prognostic parameter in patients with heart failure and reduced ejection fraction (HFrEF). Objective To evaluate the significance of RV‐PA coupling in patients with HFrEF undergoing cardiac resynchronization therapy (CRT). Methods Patients undergoing CRT in our center between January 2017 and November 2019 were eligible. Response to CRT was defined by a reduction of more than 15% of left ventricle systolic volume (LVESV) one year after CRT. Primary endpoint was a composite of HF hospitalizations and death during follow‐up. Results 54 patients (Age 64.0 ± 13.8 years; 58% male; left ventricular ejection fraction (LVEF) 28.4 ± 1.3%) were prospectively included. After a mean follow‐up of 31 ± 12.9months, the primary endpoint had occurred in 18 (33.3%) patients. A lower TAPSE/PASP ratio was associated with baseline worse HF symptoms, lower LVEF and long‐term less LV reverse remodeling (P < .05). After one year CRT improved RV systolic function (TAPSE, RV global longitudinal strain, P < .05), but not TAPSE/PASP ratio (P = .4). The ratio TAPSE/PASP (AUC=0.834) ≥ 0.58 mm/mm Hg showed good sensitivity (90%) and specificity (81.8%) for predicting response to CRT while a ratio <0.58 mm/mm Hg was associated with a higher risk of death and HF hospitalizations during the follow‐up (HR 5.37 95%CI [1.6–18], P < .001). Conclusion RV‐PA coupling evaluation using TAPSE/PASP ratio predicts CRT response. A lower TAPSE/PASP ratio is associated with a higher risk of adverse cardiovascular events.

Background: We aimed to evaluate whether right ventricle (RV) longitudinal strain indexed to pulmonary arterial systolic pressure (PASP) has prognostic significance in patients undergoing cardiac resynchronization therapy (CRT). Methods: Patients undergoing CRT were prospectively included. The primary endpoint was adverse cardiovascular events (death and HF-related hospitalizations). RV global longitudinal strain (RVGLS) and RV free wall strain (RVfwS) were measured by speckle tracking and indexed to echocardiographic estimated PASP. Results: A total of 54 patients (64.0 ± 13.8 years; 58% male) were included. After 33 ± 12.9 months, the primary endpoint occurred in 18 patients. Baseline RVGLS/PASP and RVfwS/PASP showed good discriminative ability for response to CRT (AUC = 0.88, 95% CI (0.74–1) and AUC = 0.87, 95% CI (0.77–1)). RVGLS/PASP and RVfwS/PASP were significantly associated with high risk of events at univariate analysis (HR 0.039, 95% CI (0.001–0.8) p < 0.05, respectively HR = 0.049, 95% CI (0.0033–0.72), p < 0.05). Upon multivariate Cox regression analysis, RVGLS/PASP and RVfwS/PASP remained associated with high risk of events (HR 0.018, 95% CI (0.0005–0.64), p = 0.02 and HR 0.015, 95% CI (0.0004–0.524), p = 0.01) after correction for gender, etiology, QRS duration and morphology. Conclusions: Indexing RV longitudinal strain (global and free wall) by PASP provides a parameter, which independently identifies patients with high risk of cardiovascular events and predicts non-response to CRT.