Intermediate-effect size p.Arg637Gln in FHOD3 increases risk of HCM and is associated with an aggressive phenotype in homozygous carriers.

Formin homology 2 domain-containing 3 (FHOD3) gene has emerged as one of the main non-sarcomeric genes associated with hypertrophic cardiomyopathy (HCM), but no cases of biallelic variants associated with disease have been described to date. From 2014 until 2021, FHOD3 was evaluated in our center by next-generation sequencing in 22 806 consecutive unrelated probands. The p.Arg637Gln variant in FHOD3 was enriched in our HCM cohort (284 of 9668 probands; 2.94%) compared with internal controls (64 of 11 480; 0.59%) and gnomAD controls (373 of 64 409; 0.58%), with ORs of 5.40 (95% CI: 4.11 to 7.09) and 5.19 (95% CI: 4.44 to 6.07). The variant affects a highly conserved residue localised in a supercoiled alpha helix considered a clustering site for HCM variants, and in heterozygosis can act as a predisposing factor (intermediate-effect variant) for HCM, with an estimated penetrance of around 1%. Additionally, seven homozygous carriers of p.Arg637Gln in FHOD3 were identified. All but one (unaffected) showed an early presentation and a severe HCM phenotype. All this information suggest that p.Arg637Gln variant in FHOD3 is a low-penetrant variant, with an intermediate effect, that contributes to the development of HCM in simple heterozygosis, being associated with a more severe phenotype in homozygous carriers.

Pregnancy-associated spontaneous coronary artery dissection: multidisciplinary management, challenges and literature review.

A 30-year-old woman in her second pregnancy, which was complicated by gestational diabetes mellitus. She had an uneventful spontaneous vaginal delivery at 38 weeks+3 days of gestation. Day 1 postpartum, she developed sudden chest pain radiating to her jaw and neck. Her observations were normal, and ECG showed lateral ST elevation in keeping with acute myocardial infarction. The troponin-T level was elevated at 21 ng/L at 0 hour, and >10 000 ng/L at 12 hours, respectively. Coronary angiography confirmed spontaneous dissection of the proximal left anterior descending (LAD) and proximal circumflex coronary arteries. She became unstable during percutaneous coronary intervention and consequently had a successful coronary artery bypass surgery with left saphenous vein grafts to the first obtuse marginal artery and LAD. Echocardiogram revealed moderate to severe impairment of the left ventricular function postoperatively.

Antiplatelet agents in uncertain clinical scenarios-a bleeding nightmare.

Despite over 40 years since the first percutaneous coronary intervention (PCI) was performed, the optimal dual antiplatelet therapy (DAPT) regime poses a significant challenge for clinicians, especially in certain scenarios. DAPT is the standard of care in PCI following an acute coronary syndrome (ACS) or for elective patients with obstructive coronary artery disease (CAD). There remains significant uncertainty regarding DAPT in patients at high risk of bleeding, such as the elderly and patients requiring anticoagulation. More and more clinicians are faced with a dilemma of weighing risks and benefits from the increasing list of potent, new antiplatelet agents and direct oral anticoagulants (DOACs) in a growing, aging population. Historically, most studies failed to recognize bleeding risk, instead focusing on ischemic risk. In recent years however, bleeding has been recognized as a very significant driver of morbidity and mortality in patients undergoing PCI. There is a paucity of data in this cohort leading to divergent and sometimes conflicting recommendations, largely based on expert consensus of opinion. In the current review, we critically evaluate the available evidence in these uncertain scenarios.