Major differences between men and women exist in epidemiology, manifestation, pathophysiology, treatment, and outcome of cardiovascular diseases (CVD), such as coronary artery disease, pressure overload, hypertension, cardiomyopathy, and heart failure. Corresponding sex differences have been studied in a number of animal models, and mechanistic investigations have been undertaken to analyze the observed sex differences. We summarize the biological mechanisms of sex differences in CVD focusing on three main areas, i.e., genetic mechanisms, epigenetic mechanisms, as well as sex hormones and their receptors. We discuss relevant subtypes of sex hormone receptors, as well as genomic and nongenomic, activational and organizational effects of sex hormones. We describe the interaction of sex hormones with intracellular signaling relevant for cardiovascular cells and the cardiovascular system. Sex, sex hormones, and their receptors may affect a number of cellular processes by their synergistic action on multiple targets. We discuss in detail sex differences in organelle function and in biological processes. We conclude that there is a need for a more detailed understanding of sex differences and their underlying mechanisms, which holds the potential to design new drugs that target sex-specific cardiovascular mechanisms and affect phenotypes. The comparison of both sexes may lead to the identification of protective or maladaptive mechanisms in one sex that could serve as a novel therapeutic target in one sex or in both.

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Mechanistic Pathways of Sex Differences in Cardiovascular Disease

Background Today most patients with congenital heart disease survive childhood to be cared for by adult cardiologists. The number of physicians that should be trained to manage these lesions is unknown because we do not know the number of patients. Methods To answer this question, the expected numbers of infants with each major type of congenital heart defect born in each 5-year period since 1940 were estimated from birth rates and incidence. The numbers expected to survive with or without treatment were estimated from data on natural history and the results of treatment. Finally, lesions were categorized as simple, moderate, or complex, based on the amount of expertise in management needed for optimal patient care. Results From 1940 to 2002, about 1 million patients with simple lesions, and half that number each with moderate and complex lesions, were born in the United States. If all were treated, there would be 750,000 survivors with simple lesions, 400,000 with moderate lesions, and 180,000 with complex lesions; in addition, there would be 3,000,000 subjects alive with bicuspid aortic valves. Without treatment, the survival in each group would be 400,000, 220,000, and 30,000, respectively. The actual numbers surviving will be between these 2 sets of estimates. Conclusions Survival of patients with congenital heart disease, treated or untreated, is expected to produce large numbers of adults with congenital disease, and it is likely that many more adult cardiologists will need to be trained to manage moderate and complex congenital lesions.

Prevalence of congenital heart disease

Aims: To critically review the available transcatheter aortic valve implantation techniques and their results, as well as propose recommendations for their use and development. Methods and results: A committee of experts including European Association of Cardio-Thoracic Surgery and European Society of Cardiology representatives met to reach a consensus based on the analysis of the available data obtained with transcatheter aortic valve implantation and their own experience. The evidence suggests that this technique is feasible and provides haemodynamic and clinical improvement for up to 2 years in patients with severe symptomatic aortic stenosis at high risk or with contraindications for surgery. Questions remain mainly concerning safety and long-term durability, which have to be assessed. Surgeons and cardiologists working as a team should select candidates, perform the Procedure, and assess the results. Today, the use of this technique should be restricted to high-risk patients or those with contraindication for surgery. However, this may be extended to lower risk patients if the initial promise holds to be true after careful evaluation. Conclusion: Transcatheter aortic valve implantation is a promising technique, which may offer an alternative to conventional surgery for high-risk patients with aortic stenosis. Totiay, careful evaluation is needed to avoid the risk of uncontrolled diffusion.

Transcatheter Valve Implantation for Patients with Aortic Stenosis : a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI)

Coronary artery anomalies (CAAs) are a group of congenital conditions characterized by abnormal origin or course of any of the 3 main epicardial coronary arteries. Although CAAs have been identifie...

https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.055347

Coronary Artery Anomalies.

Resumen Introduccion y objetivos Hay escasa informacion sobre la utilizacion del implante valvular aortico transcateter en pacientes con estenosis aortica grave y aorta de porcelana. El objetivo primario del estudio es analizar la mortalidad total tras el implante de una valvula percutanea CoreValve® en pacientes con estenosis aortica grave, con y sin aorta de porcelana. Metodos Estudio multicentrico, observacional y prospectivo. Se implanto una valvula aortica percutanea a 449 pacientes con estenosis aortica grave calcificada en tres hospitales. De ellos, 36 (8%) reunian criterios de aorta de porcelana. El objetivo primario fue la mortalidad total a 2 anos. Resultados El grupo con aorta de porcelana presento con mayor frecuencia arteriopatia extracardiaca (11 [30,6%] frente a 49 [11,9%]; p = 0,002), revascularizacion coronaria previa (15 [41,7%] frente a 98 [23,7%]; p = 0,017) y dislipemia (26 [72,2%] frente a 186 [45%]; p = 0,02). En este grupo se utilizo con mayor frecuencia anestesia general (15 [41,7%] frente a 111 [16,9%]; p = 0,058) y acceso axilar (9 [25%] frente a 34 [8,2%]; p = 0,004). El porcentaje de exito del procedimiento (el 94,4 frente al 97,3%; p = 0,28) y la incidencia de complicaciones (7 [19,4%] frente a 48 [11,6%]; p = 0,20) fueron similares en ambos grupos. No hubo diferencias estadisticamente significativas en el objetivo primario a los 24 meses de seguimiento (8 [22,2%] frente a 66 [16%]; p = 0,33). La presencia de complicaciones durante el implante (hazard ratio = 2,6; intervalo de confianza del 95%, 1,5-4,5; p = 0,001) fue la unica variable predictora del objetivo primario. Conclusiones El implante percutaneo con la protesis autoexpandible CoreValve® en pacientes con estenosis aortica y aorta de porcelana rechazados para cirugia de recambio valvular, es factible y seguro.

Implante percutáneo de la válvula autoexpandible CoreValve ® en pacientes con estenosis aórtica grave y aorta de porcelana: seguimiento a medio plazo

Purpose:The aim of this study was to assess the prevalence of variants and anomalies of the coronary arteries in patients with bicuspid aortic valve (BAV) and compare it with patients with tricuspid aortic valve (TAV).Materials and Methods:A total of 428 patients (193 with BAV, 235 with TAV) who und

Coronary Artery Variants and Anomalies in Patients With Bicuspid Aortic Valve.

INTRODUCTION Anaemia is defined by the Word Health Organisation as a haemoglobin level < 130 g/L for men and < 120 g/L for women [1]. It has been shown that lower haemoglobin levels are associated with increased mortality and morbidity among the elderly, and in patients with chronic heart failure or myocardial infarction [2–4]. The role of haemoglobin or haematocrit as independent predictors of mortality and morbidity in patients undergoing cardiac surgery has been described primarily in patients with coronary artery disease undergoing coronary artery bypass grafting [5, 6], as well as in patients undergoing heart valve surgery or congenital heart defects surgery [7–9]. In contrast, the predictive role of the red blood cell count (RBC) in patients undergoing valvular cardiac surgery has not been described. Given this gap in knowledge, we decided to assess a predictive value of the individual parameters of blood cell counts in patients undergoing heart valve surgery.

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Number of erythrocytes as a prognostic marker in patients undergoing heart valve surgery.

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.

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Association of the common genetic polymorphisms and haplotypes of the chymase gene with left ventricular mass in male patients with symptomatic aortic stenosis.

Introduction: Transcatheter aortic valve implantation (TAVI) is a treatment alternative for the elderly population with severe symptomatic aortic stenosis (AS) at high risk for surgical aortic valve replacement (SAVR). Aim: To assess the impact of TAVI on echocardiographic parameters of left ventricular (LV) performance and wall thickness in patients subjected to the procedure in a single-centre between 2009 and 2013. Material and methods: The initial group consisted of 170 consecutive patients with severe AS unsuitable for SAVR. Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) was 21.73 ±12.42% and mean age was 79.9 ±7.5 years. Results: The TAVI was performed in 167 (98.2%) patients. Mean aortic gradient decreased significantly more rapidly after the procedure (from 58.6 ±16.7 mm Hg to 11.9 ±4.9 mm Hg, p < 0.001). The LV ejection fraction (LVEF) significantly increased in both short-term and long-term follow-up (57 ±14% vs. 59 ±13%, p < 0.001 and 56 ±14% vs. 60 ±12%, p < 0.001, respectively). Significant regression of interventricular septum diameter at end-diastole (IVSDD) and end-diastolic posterior wall thickness (EDPWth) was noted in early (15.0 ±2.4 mm vs. 14.5 ±2.3 mm, p < 0.001 and 12.7 ±2.1 mm vs. 12.4 ±1.9 mm, p < 0.028, respectively) and late post-TAVI period (15.1 ±2.5 mm to 14.3 ±2.5 mm, p < 0.001 and 12.8 ±2.0 mm to 12.4 ±1.9 mm, p < 0.007, respectively). Significant paravalvular leak (PL) was noted in 21 (13.1%) patients immediately after TAVI and in 13 (9.6%) patients in follow-up (p < 0.001). Moderate or severe mitral regurgitation (msMR) was seen in 24 (14.9%) patients from the initial group and in 19 (11.8%) patients after TAVI (p < 0.001). Conclusions: The TAVI had an immediate beneficial effect on LVEF, LV walls thickness, and the incidence of msMR. The results of the procedure are comparable with those described in other centres.

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The impact of transcatheter aortic valve implantation on left ventricular performance and wall thickness - single-centre experience.

Background Numerous studies have shown that elevated red cell distribution width (RDW) is associated with poor outcomes in patients with cardiovascular diseases such as acute myocardial infarction, stroke, and chronic heart failure. The prognostic utility of RDW in patients with valvular disease undergoing heart valve surgery is unknown. Methods A prospective study was conducted on a group of consecutive patients with hemodynamically significant valvular heart disease that underwent elective valvular surgery. The preoperative complete blood count, data on risk factors, course of operations and the postoperative period were assessed. The primary and secondary endpoints were 30-day mortality and any major adverse event within 30 days. The data were analyzed with Kaplan-Meier survival curves, regression analyses, and receiver operator characteristic (ROC) curves. Results The study group included 500 consecutive patients who underwent replacement or repair of the valve/valves. Sixteen patients died during the follow up period. On multivariate analysis, creatinine (p = 0.04), red blood cell (RBC) count (p = 0.005) and RDW (p = 0.02) were each associated with an increased risk of death. The composite endpoint occurred in 208 patients. On multivariate analysis, chronic kidney disease (p = 0.003), raised pulmonary blood pressure (p = 0.02) and RDW (p = 0.001) remained independent predictors of the secondary endpoint. The preoperative RDW in patients with valvular disease undergoing valve surgery, combined with EuroSCORE II, predicted 30-day mortality significantly better than did EuroSCORE II alone. Conclusions An elevated RDW is associated with a worse outcome following valve surgery. The predictive ability of the RDW, when assessed by the area under the ROC curve, improved the predictive ability of the EuroSCORE II calculator.

Patrycjusz Stokłosa

Papers

Coronary Artery Variants and Anomalies in Patients With Bicuspid Aortic Valve.

Number of erythrocytes as a prognostic marker in patients undergoing heart valve surgery.

Association of the common genetic polymorphisms and haplotypes of the chymase gene with left ventricular mass in male patients with symptomatic aortic stenosis.

The impact of transcatheter aortic valve implantation on left ventricular performance and wall thickness - single-centre experience.

Red Cell Distribution Width as a Prognostic Marker in Patients Undergoing Valve Surgery.