The renin–aldosterone–angiotensin system (RAAS) plays an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2 and the host’s expression of this membrane-bound protein could affect susceptibility to infection. The RAAS is an important regulator of cardiovascular physiology and ACE2 has an essential role. People with hypertension and other traits have shown to have an imbalance in ACE/ACE2 levels and reduced levels of ACE2 could enhance the risk of adverse outcome in patients with COVID-19. It has been hypothesised that the RAAS may mediate the interplay between cardiovascular disease and COVID-19 severity. Evidence shows that antihypertensive drugs that target the RAAS have no significant effect on the risk of infection and disease outcome. Variations in RAAS genes have been associated with the risk of developing hypertension and cardiovascular disease and could partly explain the heterogenous response to SARS-CoV-2 infection. This article explores the interplay between the RAAS and COVID-19, with emphasis on the possible relationship between genetic variations and disease severity.

Left ventricle non-compaction cardiomyopathy (LVNC) has gained great interest in recent years, being one of the most controversial cardiomyopathies. There are several open debates, not only about its genetic heterogeneity, or about the possibility to be an acquired cardiomyopathy, but also about its possible overdiagnosis based on imaging techniques. In order to better understand this entity, we identified 38 LVNC patients diagnosed by cardiac MRI (CMRI) or anatomopathological study that could underwent NGS-sequencing and clinical study. Anatomopathological exam was performed in eight available LVNC hearts. The genetic yield was 34.2%. Patients with negative genetic testing had better left ventricular ejection fraction (LVEF) or it showed a tendency to improve in follow-up, and a possible trigger factor for LVNC was identified in 1/3 of them. Nonetheless, cerebrovascular accidents occurred in similar proportions in both groups. We conclude that in LVNC there seem to be different ways to achieve the same final phenotype. Genetic testing has a good genetic yield and provides valuable information. LVNC without an underlying genetic cause may have a better prognosis in terms of LVEF evolution. However, anticoagulation to prevent cerebrovascular accident (CVA) should be carefully evaluated in all patients. Larger series with pathologic examination are needed to help better understand this entity.

Familial hypercholesterolemia (FH) is an underdiagnosed genetic inherited condition that may lead to premature coronary artery disease (CAD). FH has an estimated prevalence in the general population of about 1:313. However, its prevalence in patients with premature STEMI (ST-elevation myocardial infarction) has not been widely studied. This study aimed to evaluate the prevalence of FH in patients with premature STEMI. Cardiovascular risk factors, LDLc (low-density lipoprotein cholesterol) evolution, and differences between genders were also evaluated. Consecutive patients were referred for cardiac catheterization to our center due to STEMI suspicion in 2018. From the 80 patients with confirmed premature CAD (men < 55 and women < 60 years old with confirmed CAD), 56 (48 men and eight women) accepted to be NGS sequenced for the main FH genes. Clinical information and DLCN (Dutch Lipid Clinic Network) score were analyzed. Only one male patient had probable FH (6–7 points) and no one reached a clinically definite diagnosis. Genetic testing confirmed that the only patient with a DLCN score ≥6 has HF (1.8%). Smoking and high BMI the most frequent cardiovascular risk factors (>80%). Despite high doses of statins being expected to reduce LDLc levels at STEMI to current dyslipidemia guidelines LDL targets (<55 mg/dL), LDLc control levels were out of range. Although still 5.4 times higher than in general population, the prevalence of FH in premature CAD is still low (1.8%). To improve the genetic yield, genetic screening may be considered among patients with probable or definite FH according to clinical criteria. The classical cardiovascular risk factors prevalence far exceeds FH prevalence in patients with premature STEMI. LDLc control levels after STEMI were out range, despite intensive hypolipemiant treatment. These findings reinforce the need for more aggressive preventive strategies in the young and for intensive lipid-lowering therapy in secondary prevention.

Hypertrophic cardiomyopathy (HCM) is a monogenic disease with autosomal dominant inheritance. Genotype–phenotype relationships are complex, with variable penetrance even within the same family. The involvement of other modulating genetic and environmental factors is unknown. We aimed to analyze the HCM in monozygotic twins, carriers of the same founder pathogenic variant MYBPC3 p.G263*. The relationship was verified using the PowerPlex 16 HS System kit. Phenotypic differences and environmental differences (overloading conditions, coexistence and location, lifestyle, sport, and intensity) were analyzed. Three pairs of twins genetically identical for all markers and carriers of MYBPC3 G263* were identified. No environmental differences were identified. One of the 89-year-old twins had symptomatic severe obstructive HCM that required septal ablation, while her twin has remained asymptomatic with mild phenotype >80 years. A 49-year-old twin had a severe phenotype of obstructive HCM and pending myectomy, while his twin had a mild asymptomatic phenotype. In the last pair of twins, one presented a much larger left ventricular hypertrophy than his identical twin. In summary, we present three pairs of HCM twin patients sharing not only the genetic cause of the inherited disease but the entire genetic background. Despite identical genetic information and the absence of other known clinical, environmental, or lifestyle differences, the severity of the HCM phenotype is strikingly different. These unexplained differences should prompt the study of other unknown modulating factors, either epigenetic or environmental.