Hypertrophic cardiomyopathy associated with damaging variants in the ALPK3 gene is a fairly recent discovery, and only a small number of patients have been described thus far. Here we present two additional patients with hypertrophic cardiomyopathy caused by biallelic variants in ALPK3. Genetic investigation was performed using a targeted gene panel consisting of known cardiomyopathy-associated genes and whole exome sequencing. The patients showed a large difference in the age of onset, and both presented with extracardiac features that are often seen in ALPK3 patients. The patient with the later onset showed milder extracardiac symptoms, such as decreased muscle tone and distal muscular dystrophy, but had fast progression of cardiac complications leading to the need of heart transplantation. This study further elucidates the variability of both symptoms and age of onset among these patients.

Aims: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial prespecified an analysis to determine whether accounting for recurrent cardiovascular events in addition to first events modified understanding of the treatment effects. Methods and results: Patients with stable coronary artery disease (CAD) and moderate or severe ischaemia on stress testing were randomized to either initial invasive (INV) or initial conservative (CON) management. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and hospitalization for unstable angina, heart failure, or cardiac arrest. The Ghosh–Lin method was used to estimate mean cumulative incidence of total events with death as a competing risk. The 5179 ISCHEMIA patients experienced 670 index events (318 INV, 352 CON) and 203 recurrent events (102 INV, 101 CON). A single primary event was observed in 9.8% of INV and 10.8% of CON patients while ≥2 primary events were observed in 2.5% and 2.8%, respectively. Patients with recurrent events were older; had more frequent hypertension, diabetes, prior MI, or cerebrovascular disease; and had more multivessel CAD. The average number of primary endpoint events per 100 patients over 4 years was 18.2 in INV [95% confidence interval (CI) 15.8–20.9] and 19.7 in CON (95% CI 17.5–22.2), difference −1.5 (95% CI −5.0 to 2.0, P = 0.398). Comparable results were obtained when all-cause death was substituted for cardiovascular death and when stroke was added as an event. Conclusions: In stable CAD patients with moderate or severe myocardial ischaemia enrolled in ISCHEMIA, an initial INV treatment strategy did not prevent either net recurrent events or net total events more effectively than an initial CON strategy. Clinical trial registration: ISCHEMIA ClinicalTrials.gov number, NCT01471522, https://clinicaltrials.gov/ct2/show/NCT01471522.

Background: Women with chronic coronary disease have more frequent angina and worse health status than men, despite having less coronary artery disease (CAD). We examined whether perceived stress and depressive symptoms mediate sex differences in angina, and whether this relationship differs in the setting of obstructive CAD or ischemia with no obstructive coronary artery disease (INOCA). Methods: We analyzed the association between sex, stress (Perceived Stress Scale‐4) and depressive symptoms (Patient Health Questionnaire‐8) on angina‐related health status (Seattle Angina Questionnaire [SAQ]) at enrollment in the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial and CIAO‐ISCHEMIA (Changes in Ischemia and Angina Over 1 Year Among ISCHEMIA Trial Screen Failures With No Obstructive CAD on Coronary CT [Computed Tomography] Angiography) ancillary study. Results: Scores for the SAQ, Perceived Stress Scale‐4, and Patient Health Questionnaire‐8 were available in 1626 participants (N=1439 CAD and N=187 INOCA). Women had lower (worse) SAQ‐7 summary scores than men in both CAD and INOCA cohorts (CAD: median 76 [25th, 75th percentiles 60, 90] versus 83 [70, 96], P <0.001; INOCA: 80 [64,89] versus 85 [75, 93], P =0.012). Higher stress and depressive symptoms were associated with worse angina in both cohorts. Female sex, Perceived Stress Scale‐4 score, and Patient Health Questionnaire‐8 score were each independently associated with lower SAQ summary score, but CAD versus INOCA cohort was not. There was no interaction between sex and stress (−0.39 [95% CI, –1.01 to 0.23]) or sex and depression (−0.00 [95% CI, –0.53 to 0.53]) on SAQ summary score. Conclusions: High stress and depressive symptoms were independently associated with worse angina and poorer health status, without interaction with sex with or without obstructive CAD. Factors other than stress or depression contribute to worse health status in women with obstructive CAD or INOCA. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02347215, NCT01471522.

Роль мышечной ткани в патогенезе хронической сердечной недостаточности — возможности воздействия (исследование “ФОРМА”)

The article presents a literature review on physical rehabilitation (PR) in patients with the new coronavirus infection (COVID-19) of extremely severe, severe and moderate course in acute (in the intensive care unit, ICU) and subacute (immediately after transfer from the ICU) stage of the disease in a pandemic. The authors defined the aims and principles of medical rehabilitation assistance, the appropriate amount of PR exercises, and the mechanism of interaction between the rehabilitation staff and the ICU, in conditions of increased risk of infection of medical personnel. PR programs and therapeutic exercises complexes for different clinical situations (patient models) are proposed, depending on the severity of the patient’s condition, medical care conditions and the need for various respiratory support.