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.

The accelerated streptokinase regimen was well tolerated and resulted in a significantly higher coronary reperfusion rate and significantly lower mortality compared with the traditional regimen. The 0.75 streptokinase + enoxaparin combination was at least as efficacious as the 0.75 streptokinase + UFH combination and is preferred because of its ease of administration and predictable anticoagulant effect.

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A 40-year-old man without risk factors presented to the emergency department after a recurrent syncope at rest. Despite his excessive abdominal fat, he underwent physical training (2 h every day). Family history disclosed that his father had died suddenly during sleep at the age of 43 years. Laboratory tests were normal. Baseline ECG showed a sinus rhythm of 91 bpm, first-degree atrioventricular block (PR 220 ms), narrow QRS complex (90 ms) with incomplete right bundle branch block morphology and discrete ST-segment elevation of <0.1 in lead V1 (figure 1A). Intravenous ajmaline (1 mg/kg/5 min) 1 failed to induce diagnostic ECG changes (figure 1B), even after placement of the right precordial leads in a superior position to the third (figure 1C) and second (figure 1D) intercostal space. 1 However, at the end of maximal inspiration a type 1 Brugada pattern was reproducibly observed (figure 1E). The patient received an implantable cardioverter-defibrillator and was discharged. After 6 months he received one shock during sleep for fast ventricular tachycardia degenerating into ventricular fibrillation.Regional conduction delays and local activation gradient reduction on the free right ventricle outflow tract wall have been described in Brugada syndrome. 2 Deep inspiration may unmask a Brugada ECG owing to diaphragmatic descent with heart counterclockwise axial rotation (exposing the right ventricle outflow tract wall), augmented right ventricular filling (increased wall stress amplifying conduction anomalies) and, possibly, augmented vagal tone. The high incidence of ventricular arrhythmias during sleep may also be explained by the respiratory variations in disease expression during apnoea episodes.

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