We investigated the association between polymorphisms and haplotypes of the chymase 1 gene (CMA1) and the left ventricular mass index (LVM/BSA) in a large cohort of patients with aortic stenosis (AS). Additionally, the gender differences in cardiac remodeling and hypertrophy were analyzed. The genetic background may affect the myocardial response to pressure overload. In human cardiac tissue, CMA1 is involved in angiotensin II production and TGF-β activation, which are two major players in the pathogenesis of hypertrophy and fibrosis. Preoperative echocardiographic data from 648 patients with significant symptomatic AS were used. The LVM/BSA was significantly lower (p<0.0001), but relative wall thickness (RWT) was significantly higher (p = 0.0009) in the women compared with the men. The haplotypes were reconstructed using six genotyped polymorphisms: rs5248, rs4519248, rs1956932, rs17184822, rs1956923, and rs1800875. The haplotype h1.ACAGGA was associated with higher LVM/BSA (p = 9.84×10⁻⁵), and the haplotype h2.ATAGAG was associated with lower LVM/BSA (p = 0.0061) in men, and no significant differences were found in women. Two polymorphisms within the promoter region of the CMA1 gene, namely rs1800875 (p = 0.0067) and rs1956923 (p = 0.0015), influenced the value of the LVM/BSA in males. The polymorphisms and haplotypes of the CMA1 locus are associated with cardiac hypertrophy in male patients with symptomatic AS. Appropriate methods for the indexation of heart dimensions revealed substantial sex-related differences in the myocardial response to pressure overload.

Background: The purpose of this retrospective study was to investigate outcomes of patients with severe coronary artery disease (CAD) after implementing various treatment strategies following multidisciplinary Heart Team (MHT) discussion. Methods Primary and secondary endpoints and quality of life during a mean (SD) follow-up of 37 (14) months of patients with severe CAD (three-vessel [3-VD] or/and left main [LM] disease) qualified after MHT discussion to optimal medical treatment (OMT) alone, OMT and coronary artery bypass grafting (CABG), or OMT and percutaneous coronary intervention (PCI) were evaluated. As the primary endpoint, major adverse cardiac or cerebrovascular events (MACCE) (i.e., death from any cause, stroke, myocardial infarction, or repeat/need for revascularization) were considered. Result: From 2016 to 2019, 176 MHT meetings were held, and a total of 1286 participants with severe CAD and completely implemented MHT decisions (OMT, CABG, or PCI for 251, 356, and 679 patients, respectively) were included. The occurrence of the primary endpoint was significantly increased in OMT-group (154 (61.4%) vs. CABG and PCI groups—110 (30.9%) and 302 (44.5%) patients, respectively (p < 0.05). For interventional strategies only—CABG was associated with reduced rates of MACCE and repeat revascularization, while the superiority of PCI for stroke and disabling stroke was observed (p < 0.05). The general health status assessed at the end of the follow-up was significantly better for patients who underwent CABG or PCI than in the OMT group (p < 0.05). Conclusions: In this real-life study, we presented a single-center experience of providing optimal medical care for patients with severe CAD following MHT discussion.

Renalase decreases circulating catecholamines concentration and is important in maintaining primary cellular metabolism. Renalase acts through the plasma membrane calcium ATPase 4b in the heart, which affects pressure overload but not exercise induced heart hypertrophy. The aim of this study was to test the association between a functional polymorphism Glu37Asp (rs2296545) of the renalase gene and left ventricular hypertrophy in a large cohort of patients with aortic stenosis. The study group consisted of 657 patients with aortic stenosis referred for aortic valve replacement. Preoperative echocardiographic assessment was performed to obtain cardiac phenotypes. Generalized-linear models were implemented to analyze data using crude or full model adjusted for selected clinical factors. In females, the Asp37 variant of the Glu37Asp polymorphism was associated with higher left ventricular mass (p = 0.0021 and p = 0.055 crude and full model respectively), intraventricular septal thickness (p = 0.0003 and p = 0.0143) and posterior wall thickness (p = 0.0005 and p = 0.0219) all indexed to body surface area, as well as relative wall thickness (p = 0.001 and p = 0.0097). No significant associations were found among the male patients. In conclusion, we have found the association of the renalase Glu37Asp polymorphism with left ventricle hypertrophy in large group of females with aortic stenosis. The Glu37Asp polymorphism causes not only amino-acid substitution in FAD binding domain but may also change binding affinity of the hypoxia- and hypertrophy-related transcription factors and influence renalase gene expression. Our data suggest that renalase might play a role in hypertrophic response to pressure overload, but the exact mechanism requires further investigation.

Background: This retrospective study was proposed to investigate outcomes of patients with severe aortic stenosis (AS) after implementation of various treatment strategies following dedicated Heart Team (HT) decisions. Methods: Primary and secondary endpoints and quality of life during a median follow-up of 866 days of patients with severe AS qualified after HT discussion to: optimal medical treatment (OMT) alone, OMT and transcather aortic valve replacement (TAVR) or OMT and surgical aortic valve replacement (SAVR) were evaluated. As the primary endpoint composite of all-cause mortality, non-fatal disabling strokes and non-fatal rehospitalizations for AS were considered, while other clinical outcomes were determined as secondary endpoints. Results: From 2016 to 2019, 176 HT meetings were held, and a total of 482 participants with severe AS and completely implemented HT decisions (OMT, TAVR and SAVR for 79, 318 and 85, respectively) were included in the final analysis. SAVR and TAVR were found to be superior to OMT for primary and all secondary endpoints (p < 0.05). Comparing interventional strategies only, TAVR was associated with reduced risk of acute kidney injury, new onset of atrial fibrillation and major bleeding, while the superiority of SAVR for major vascular complications and need for permanent pacemaker implantation was observed (p < 0.05). The quality of life assessed at the end of follow-up was significantly better for patients who underwent TAVR or SAVR than in OMT-group (p < 0.05). Conclusions: We demonstrated that after careful implementation of HT decisions interventional strategies compared to OMT only provide superior outcomes and quality of life for patients with AS.

Background: Obstructive sleep apnea is associated with an increased prevalence of cardiovascular disease. The mechanism of these associations is not completely understood. We aimed to investigate the association of the apnea hypopnea index and the degree of airflow limitation with endothelial dysfunction. Methods: This was a single-center prospective study of patients admitted for diagnostic coronary angiography (CAG). Endothelial function was assessed by the non-invasive EndoPAT system by reactive hyperemia index (RHI) and divided into two groups: endothelial dysfunction and normal endothelial function. Sleep apnea signs were detected by WatchPAT measuring the respiratory disturbance index (pRDI), the apnea and hypopnea index (pAHI), and the oxygen desaturation index (ODI). Patients underwent spirometry and body plethysmography. Based on CAG, the severity of coronary artery disease was assessed as follows: no significant coronary artery disease, single-, two- and three-vessel disease. Results: A total of 113 patients were included in the study. Breathing disorders measured by WatchPAT and spirometry were more severe in patients with endothelial dysfunction: pRDI (27.3 vs. 14.8, p = 0.001), pAHI (24.6 vs. 10.3, p < 0.001), ODI (13.7 vs. 5.2, p = 0.002), forced expiratory volume in one second (FEV₁) (81.2 vs. 89, p = 0.05). In a multivariate regression analysis, pAHI and FEV₁ were independent predictors of endothelial dysfunction assessed by RHI. There was no correlation between the severity of coronary artery disease and endothelial dysfunction. Conclusions: Obstructive sleep apnea signs and greater airflow limitation were associated with endothelial dysfunction regardless of the severity of the coronary artery disease.