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.

Enfermedad cardiovascular tras infección por SARS-CoV-2 en pacientes ancianos. Resultados del seguimiento anual de una cohorte de supervivientes / Cardiovascular disease after COVID-19 infection in elderly patients. Results of annual follow-up of a cohort of survivors

Introducción: Si bien el impacto de la infección por SARS-CoV-2 sobre el sistema cardiovascular es conocido en fase aguda, la repercusión cardiovascular de la población anciana superviviente a la infección respiratoria por la COVID-19 a largo plazo no ha sido suficientemente estudiada.Métodos: Registro observacional de 240 pacientes ancianos (75 o más años), ingresados de forma consecutiva por infección respiratoria por la COVID-19 y supervivientes a la misma, entre el 1 de marzo y el 30 abril de 2020, en el Hospital General Universitario de Ciudad Real. Se analizó de forma prospectiva la incidencia de eventos cardiovasculares mayores (MACE) (mortalidad cardiovascular, síndrome coronario agudo, accidente cerebrovascular, enfermedad tromboembólica e insuficiencia cardiaca).Resultados: La edad media fue de 83,75±5,75 años. Tras un seguimiento medio de 352,2±70,4 días el 13,8% de los pacientes falleció y el 9,6% presentó MACE, siendo el más frecuente la insuficiencia cardiaca, sin diferencias en la gravedad ni evolución general de la enfermedad aguda. En el modelo de regresión de Cox multivariante el riesgo de desarrollar MACE fue mayor en los pacientes con enfermedad pulmonar obstructiva crónica (HR 4,29; IC 95% 1,62-11,39; p=0,003) y diurético de asa (HR 2,99; IC 95% 1,27-7,07; p=0,01).Conclusiones: En población anciana superviviente a la COVID-19 la incidencia de MACE tras un año de seguimiento es elevada, siendo la principal manifestación la insuficiencia cardiaca. (AU)

Introduction: Although the effects of SARS-CoV-2 infection on the cardiovascular system is well known in the acute phase, the cardiovascular impact of the elderly population surviving COVID-19 respiratory infection after 1 year of follow-up has not been sufficiently studied.Methods: Observational registry of 240 elderly patients (75 years or older), consecutively admitted for COVID-19 respiratory infection and survivors of the same, between March 1 and April 30, 2020, at the Hospital General Universitario de Ciudad Real. The incidence of major cardiovascular events [MACE] (cardiovascular death [CD], acute coronary syndrome [ACS], cerebrovascular disease [CVD], venous thromboembolic disease [VTE] and heart failure [HF]) was prospectively analysed.Results: The mean age was 83.75±5.75 years. After a mean follow-up of 352.2±70.4 days, 13.8% of patients died and 9.6% had MACE, the most frequent being heart failure, with no differences in severity or overall course of acute illness. In the multivariate Cox regression model, the risk of developing MACE was higher in patients with chronic obstructive pulmonary disease and (HR 4.29; 95%CI 1.62-11.39; P=.003) and loop diuretic (HR 2.99; 95%CI 1.27-7.07; P=.01).Conclusions: In elderly COVID-19 survivors, the incidence of MACE after one year of follow-up is high, the main manifestation being heart failure.