Bonita, Raphael

ABSTRACT Background Patients with hypertrophic obstructive cardiomyopathy (HOCM) were excluded from all major trials for transcatheter aortic valve replacement (TAVR). “Suicide left ventricle” occurring after TAVR is postulated to occur as a result of chronic pressure overload from fixed obstruction that is acutely relieved after the valve deployment resulting in worsening left ventricular outflow tract obstruction. Aims The aim of this study was to determine the clinical and readmission outcomes in HOCM patients undergoing TAVR. Methods Data was extracted from the National Inpatient and National Readmission 2016−2020 Databases. We performed multivariable Logistic regression analysis to determine the odds of in‐hospital mortality and other relevant clinical outcomes in patients undergoing TAVR with and without comorbid HOCM. Multivariable Cox regression analysis was used to assess 30‐day hospital readmission in HOCM patients undergoing TAVR. Results We identified 296,670 patients who underwent TAVR, of whom 534 (0.2%) had comorbid HOCM. The patients undergoing TAVR with comorbid HOCM had more than threefold higher risk of in‐hospital mortality (adjusted odds ratio: 3.47, 95% CI 1.37–8.81, p = 0.009) when compared to patients without HOCM. Additionally, patients undergoing TAVR with comorbid HOCM had a higher risk of atrioventricular blocks, cardiogenic shock, acute kidney injury, and the need for intubation. There was no difference in readmission outcomes post‐TAVR among patients with and without HOCM. Conclusion Our analysis of a large, real‐world cohort of patients undergoing TAVR showed that patients with HOCM have a significantly higher risk of in‐hospital mortality and procedural complications when compared to patients without HOCM.

Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator–activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.