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Background: Patients with aortic stenosis may continue to have an increased risk of heart failure, arrhythmias, and death after successful transcatheter aortic valve implantation. Renin-angiotensin system inhibitors may be beneficial in this setting. We aimed to explore whether ramipril improves the outcomes of patients with aortic stenosis after transcatheter aortic valve implantation., Methods and Results: PROBE (Prospective Randomized Open, Blinded Endpoint) was a multicenter trial comparing ramipril with standard care (control) following successful transcatheter aortic valve implantation in patients with left ventricular ejection fraction >40%. The primary end point was the composite of cardiac mortality, heart failure readmission, and stroke at 1-year follow-up. Secondary end points included left ventricular remodeling and fibrosis. A total of 186 patients with median age 83 years (range 79-86), 58.1% women, and EuroSCORE-II 3.75% (range 3.08-4.97) were randomized to receive either ramipril (n=94) or standard treatment (n=92). There were no significant baseline, procedural, or in-hospital differences. The primary end point occurred in 10.6% in the ramipril group versus 12% in the control group ( P =0.776), with no differences in cardiac mortality (ramipril 1.1% versus control group 2.2%, P =0.619) but lower rate of heart failure readmissions in the ramipril group (3.2% versus 10.9%, P =0.040). Cardiac magnetic resonance analysis demonstrated better remodeling in the ramipril compared with the control group, with greater reduction in end-systolic and end-diastolic left ventricular volumes, but nonsignificant differences were found in the percentage of myocardial fibrosis., Conclusions: Ramipril administration after transcatheter aortic valve implantation in patients with preserved left ventricular function did not meet the primary end point but was associated with a reduction in heart failure re-admissions at 1-year follow-up., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03201185.

Background: Morbidly obese (MO) patients are increasingly undergoing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) for severe aortic stenosis (AS). However, the best therapeutic strategy for these patients remains a matter for debate., Aims: Our aim was to compare the periprocedural and mid-term outcomes in MO patients undergoing TAVR versus SAVR., Methods: A multicentre retrospective study including consecutive MO patients (body mass index ≥40 kg/m 2 , or ≥35 kg/m 2 with obesity-related comorbidities) from 18 centres undergoing either TAVR (n=860) or biological SAVR (n=696) for severe AS was performed. Propensity score matching resulted in 362 pairs., Results: After matching, periprocedural complications, including blood transfusion (14.1% versus 48.1%; p<0.001), stage 2-3 acute kidney injury (3.99% versus 10.1%; p=0.002), hospital-acquired pneumonia (1.7% versus 5.8%; p=0.005) and access site infection (1.5% versus 5.5%; p=0.013), were more common in the SAVR group, as was moderate to severe patient-prosthesis mismatch (PPM; 9.9% versus 39.4%; p<0.001). TAVR patients more frequently required permanent pacemaker implantation (14.4% versus 5.6%; p<0.001) and had higher rates of ≥moderate residual aortic regurgitation (3.3% versus 0%; p=0.001). SAVR was an independent predictor of moderate to severe PPM (hazard ratio [HR] 1.80, 95% confidence interval [CI]: 1.25-2.59; p=0.002), while TAVR was not. In-hospital mortality was not different between groups (3.9% for TAVR versus 6.1% for SAVR; p=0.171). Two-year outcomes (including all-cause and cardiovascular mortality, and readmissions) were similar in both groups (log-rank p>0.05 for all comparisons). Predictors of all-cause 2-year mortality differed between the groups; moderate to severe PPM was a predictor following SAVR (HR 1.78, 95% CI: 1.10-2.88; p=0.018) but not following TAVR (p=0.737)., Conclusions: SAVR and TAVR offer similar mid-term outcomes in MO patients with severe AS, however, TAVR offers some advantages in terms of periprocedural morbidity.

Background: Renal dysfunction in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) indicates a poor long-term prognosis. However, the prognostic value of the improvement or stabilisation of renal function during follow-up has not yet been assessed. This study aimed to investigate the long-term predictive impact of the improvement or stabilisation of renal function after one year of follow-up in patients with STEMI undergoing pPCI with renal dysfunction at discharge., Methods: This prospective, single-centre cohort study included 2170 consecutive patients with STEMI who underwent pPCI. The glomerular filtration rate (GFR) was determined at hospital discharge and one-year follow-up. The median clinical follow-up was 72 months., Results: Among the 2004 patients, 393 (19.6%) had a GFR <60 ml/min, and 1611 (80.4%) had a GFR ≥ 60 ml/min at discharge. Among patients with GFR <60 ml/min, data at one-year follow-up were available for 342. Of these patients, 127 (32%) showed improvement in renal function (defined as improvement in the Kidney Disease Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) classification), 47 (12%) showed worsening of renal function (defined as worsening of the KDIGO CKD classification), and 168 (43%) showed no category changes. Improvement or stabilisation of GFR at one year of follow-up was associated with a reduction of major adverse cardiovascular events (MACE) [HR 0.51, 95% CI: 0.35-0.75, p = 0.001] and all-cause mortality [HR 0.54, 95% CI: 0.34-0.84, p = 0.007] during follow-up., Conclusions: The improvement or stabilisation of renal function at one-year follow-up in patients with STEMI and renal dysfunction is associated with a better long-term prognosis., Competing Interests: Conflicts of interest None., (Copyright © 2022 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Aim: Whether Takotsubo syndrome (TTS) should be classified within myocardial infarction with non-obstructive coronary arteries (MINOCAs) is still controversial. The aim of this work was to evaluate the main differences between TTS and non-TTS MINOCAs., Methods and Results: A cohort study based on two prospective registries: TTS from the RETAKO registry ( N :1,015) and patients with non-TTS MINOCAs from contemporary records of acute myocardial infarction from five 5 national centers ( N :1,080). Definitions and management recommended by the ESC were used. Survival analysis was based on the Cox regression analysis; propensity score matching (PS) was created to adjust prognostic variables. Takotsubo syndrome were more often women (85.9 vs. 51.9%; p < 0.001) and older (69.4 ± 12.5 vs. 64.5 ± 14.1 years; p < 0.001). Atrial fibrillation (AF) was more frequent in non-TTS MINOCAs (10.4 vs. 14.4%; p = 0.007). Psychiatric disorders were more prevalent in TTS (15.5 vs. 10.2%, p < 0.001). In-hospital mortality and complications were higher in TTS: 3.4 vs. 1.8%, ( p = 0.015), and 25.8 vs. 11.5%, ( p < 0.001). Global mortality before PS matching was 16.1% in non-TTS MINOCAs and 8.1% in TTS. Median follow-up was 32.4 months; after PS matching, TTS had fewer major adverse cardiovascular events (MACEs): hazard ratio (HR) 0.59; 95% CI 0.42-0.83. There were no differences in global mortality (HR 0.87; CI: 0.64-1.19), but TTS had lower cardiovascular mortality (HR 0.58; CI: 0.35-0.98)., Conclusion: Compared to the rest of MINOCAs, TTS presents a different patient profile and a more aggressive acute phase. However, its long-term cardiovascular prognosis is better. These results support that TTS should be considered a separate entity with unique characteristics and prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RS-R declared a shared affiliation with one of the authors, IM to the handling editor at time of review., (Copyright © 2022 Lopez-Pais, Izquierdo Coronel, Raposeiras-Roubín, Álvarez Rodriguez, Vedia, Almendro-Delia, Sionis, Martin-Garcia, Uribarri, Blanco, Martín de Miguel, Abu-Assi, Galán Gil, Sestayo Fernández, Espinosa Pascual, Agra-Bermejo, López Otero, García Acuña, Alonso Martín, Gonzalez-Juanatey, Perez de Juan Romero and Núñez-Gil.)

Deterioration is sometimes unexpected in SARS-CoV2 infection. The aim of our study is to establish laboratory predictors of mortality in COVID-19 disease which can help to identify high risk patients. All patients admitted to hospital due to Covid-19 disease were included. Laboratory biomarkers that contributed with significant predictive value for predicting mortality to the clinical model were included. Cut-off points were established, and finally a risk score was built. 893 patients were included. Median age was 68.2 ± 15.2 years. 87(9.7%) were admitted to Intensive Care Unit (ICU) and 72(8.1%) needed mechanical ventilation support. 171(19.1%) patients died. A Covid-19 Lab score ranging from 0 to 30 points was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included haemoglobin, erythrocytes, leukocytes, neutrophils, lymphocytes, creatinine, C-reactive protein, interleukin-6, procalcitonin, lactate dehydrogenase (LDH), and D-dimer. Three groups were established. Low mortality risk group under 12 points, 12 to 18 were included as moderate risk, and high risk group were those with 19 or more points. Low risk group as reference, moderate and high patients showed mortality OR 4.75(CI95% 2.60-8.68) and 23.86(CI 95% 13.61-41.84), respectively. C-statistic was 0-85(0.82-0.88) and Hosmer-Lemeshow p-value 0.63. Covid-19 Lab score can very easily predict mortality in patients at any moment during admission secondary to SARS-CoV2 infection. It is a simple and dynamic score, and it can be very easily replicated. It could help physicians to identify high risk patients to foresee clinical deterioration.

Introduction and Objectives: Coronavirus disease (COVID-19) has been designated a global pandemic by the World Health Organization. It is unclear whether previous treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) affects the prognosis of COVID-19 patients. The aim of this study was to evaluate the clinical implications of previous treatment with ACEI/ARB on the prognosis of patients with COVID-19 infection., Methods: Single-center, retrospective, observational cohort study based on all the inhabitants of our health area. Analyses of main outcomes (mortality, heart failure, hospitalization, intensive care unit [ICU] admission, and major acute cardiovascular events [a composite of mortality and heart failure]) were adjusted by multivariate logistic regression and propensity score matching models., Results: Of the total population, 447 979 inhabitants, 965 patients (0.22%) were diagnosed with COVID-19 infection, and 210 (21.8%) were under ACEI or ARB treatment at the time of diagnosis. Treatment with ACEI/ARB (combined and individually) had no effect on mortality (OR, 0.62; 95%CI, 0.17-2.26; P  = .486), heart failure (OR, 1.37; 95%CI, 0.39-4.77; P  = .622), hospitalization rate (OR, 0.85; 95%CI, 0.45-1.64; P  = .638), ICU admission (OR, 0.87; 95%CI, 0.30-2.50; P  = .798), or major acute cardiovascular events (OR, 1.06; 95%CI, 0.39-2.83; P  = .915). This neutral effect remained in a subgroup analysis of patients requiring hospitalization., Conclusions: Previous treatment with ACEI/ARB in patients with COVID-19 had no effect on mortality, heart failure, requirement for hospitalization, or ICU admission. Withdrawal of ACEI/ARB in patients testing positive for COVID-19 would not be justified, in line with current recommendations of scientific societies and government agencies., (© 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Limited data are available regarding change in the nutritional status after transcatheter aortic valve replacement (TAVR). This study evaluated the prognostic impact of the change in the geriatric nutritional risk index following TAVR., Methods: TAVR patients were analyzed in a prospective and observational study. To analyze the change in nutritional status, geriatric nutritional risk index of the patients was calculated on the day of TAVR and at 3-month follow-up. The impact of the change in nutritional risk index after TAVR on all-cause mortality, heart failure hospitalization (HF-h), and the composite of all-cause death and HF hospitalization was analyzed using the Cox Proportional Hazards model., Results: Four hundred thirty-three patients were included. After TAVR, 68.4% (n=182) patients with baseline nutritional risk improved compared with 31.6% (n=84) who remained at nutritional risk. The change from no-nutritional risk to nutritional risk after TAVR occurred in 15.0% (n=25), while 85.0% (n=142) remained without risk of malnutrition. During follow-up, 157 (36.3%) patients died and 172 patients (39.7%) were hospitalized due to HF. Patients who continued to be at nutritional risk had a higher risk of mortality (hazard ratio [HR], 2.10 [95% CI, 1.30-3.39], P =0.002), HF-h (HR, 1.97 [95% CI, 1.26-3.06], P =0.000), and the composite of death and HF-h (HR, 2.0 [95% CI, 1.37-2.91], P <0.001). The change to non-nutritional risk after TAVR significantly impacted mortality (HR, 0.48 [95% CI, 0.30-0.78], P =0.003), HF-h (HR, 0.50 [95% CI, 0.34-0.74], P =0.001), and the composite outcome (HR, 0.44 [95% CI, 0.32-0.62], P <0.001)., Conclusions: Remaining at nutritional risk after TAVR confers a poor prognosis and is associated with an increased risk of mortality and HF-h, while the change from risk of malnutrition to non-nutritional risk after TAVR was associated with a halving of the risk of mortality and HF-h. Further studies are needed to identify whether patients at nutritional risk would benefit from nutritional intervention during processes of care of TAVR programs.

Background The clinical significance of conduction disturbances after transcatheter aortic valve implantation has been described; however, little is known about the influence of baseline ECGs in the prognosis of these patients. Our aim was to study the influence of baseline ECG parameters, including interatrial block (IAB), in the prognosis of patients treated with transcatheter aortic valve implantation. Methods and Results The BIT (Baseline Interatrial Block and Transcatheter Aortic Valve Implantation) registry included 2527 patients with aortic stenosis treated with transcatheter aortic valve implantation. A centralized analysis of baseline ECGs was performed. Patients were divided into 4 groups: normal P wave duration (<120 ms); partial IAB (P wave duration ≥120 ms, positive in the inferior leads); advanced IAB (P wave duration ≥120 ms, biphasic [+/-] morphology in the inferior leads); and nonsinus rhythm (atrial fibrillation/flutter and paced rhythm). The mean age of patients was 82.6±9.8 years and 1397 (55.3%) were women. A total of 960 patients (38.0%) had a normal P wave, 582 (23.0%) had partial IAB, 300 (11.9%) had advanced IAB, and 685 (27.1%) presented with nonsinus rhythm. Mean follow-up duration was 465±171 days. Advanced IAB was the only independent predictor of all-cause mortality (hazard ratio [HR], 1.48; 95% CI, 1.10-1.98 [ P =0.010]) and of the composite end point (death/stroke/new atrial fibrillation) (HR, 1.51; 95% CI, 1.17-1.94 [ P =0.001]). Conclusions Baseline ECG characteristics influence the prognosis of patients with aortic stenosis treated with transcatheter aortic valve implantation. Advanced IAB is present in about an eighth of patients and is associated with all-cause death and the composite end point of death, stroke, and new atrial fibrillation during follow-up.

Background: Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory-syndrome coronavirus-2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2. This interaction has been proposed as a potential risk factor in patients treated with RAAS inhibitors., Objectives: This study analyzed whether RAAS inhibitors modify the risk for COVID-19., Methods: The RASTAVI (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation) trial is an ongoing randomized clinical trial randomly allocating subjects to ramipril or control groups after successful transcatheter aortic valve replacement at 14 centers in Spain. A non-pre-specified interim analysis was performed to evaluate ramipril's impact on COVID-19 risk in this vulnerable population., Results: As of April 1, 2020, 102 patients (50 in the ramipril group and 52 in the control group) were included in the trial. Mean age was 82.3 ± 6.1 years, 56.9% of the participants were male. Median time of ramipril treatment was 6 months (interquartile range: 2.9 to 11.4 months). Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving ramipril; hazard ratio: 1.150; 95% confidence interval: 0.351 to 3.768). The risk of COVID-19 was increased in older patients (p = 0.019) and those with atrial fibrillation (p = 0.066), lower hematocrit (p = 0.084), and more comorbidities according to Society of Thoracic Surgeons score (p = 0.065). Admission and oxygen supply was required in 4.9% of patients (2 in the ramipril group and 3 in the control group), and 4 of them died (2 in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p = 0.039)., Conclusions: In a high-risk population of older patients with cardiovascular disease, randomization to ramipril had no impact on the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS inhibitor treatment during the COVID-19 crisis. (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation [RASTAVI]; NCT03201185)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The platelet-specific collagen receptor glycoprotein VI (GPVI) is critical for the formation of arterial thrombosis in vivo. We analyzed GPVI-activated platelets from ST-elevation myocardial infarction (STEMI) patients and matched stable coronary artery disease (SCAD) controls in order to provide novel clues on the degree of involvement of GPVI signaling in the acute event. Firstly, platelets were isolated from systemic venous blood and activated with the GPVI specific agonist CRP (collagen-related peptide). STEMI and SCAD samples were compared by a phosphoproteomics approach. Validations were by immunoblotting in systemic and intracoronary blood from independent cohorts of patients. Twenty-six differentially regulated proteins were identified when comparing CRP-activated systemic platelets from STEMI and SCAD patients, 4 of which were selected for validation studies: PLCɣ2, G6f, SLP-76, and Dok-2. Immunoblot analyses showed these four proteins had higher tyrosine phosphorylation levels in response to CRP in platelets from STEMI patients, being these levels more pronounced at the culprit site of coronary artery occlusion. Moreover, platelet aggregation studies showed a higher response to GPVI agonists in STEMI patients compared to SCAD controls. In conclusion, we show an altered activation state of GPVI signaling in STEMI patients, confirming this receptor as a promising anti-thrombotic target for myocardial infarction.

Background: The mobilisation process of endothelial progenitor cells (EPC) after stent implantation by percutaneous coronary intervention (PCI) is unclear because the circulating EPC levels are influenced by several pathophysiological factors. The objective was to analyse the kinetics of EPC concentration following elective PCI in patients with stable angina, and its relation with other biomarkers or parameters of cardiovascular function., Methods: Pilot study in stable angina patients (n = 30) for elective PCI and implantation of bare-metal stent (BMS), drug-eluting stent (DES) or EPC-capturing stent (ECS). Samples were taken at baseline, 6 h, 24 h and 6 months after PCI for biochemical analysis and EPC quantification by flow cytometry., Results: Baseline EPC levels, quantified in peripheral blood, were related with the extent of the coronary lesion and the percentage of stenosis. EPC concentration increased 6 hours after PCI in relation with plasma C-reactive protein concentration and returned to basal levels after 24 hours post-PCI., Conclusions: Baseline EPC levels are related with the extension of the lesion and stenosis whereas the kinetics of EPC mobilization showed to be related with C-reactive protein concentration. Endothelial activation seems to occur in response to EPC mobilization or vascular damage by PCI.

Objective: To evaluate immediate transcatheter aortic valve implantation (TAVI) results and medium-term follow-up in very elderly patients with severe and symptomatic aortic stenosis (AS)., Methods: This multicenter, observational and prospective study was carried out in three hospitals. We included consecutive very elderly (> 85 years) patients with severe AS treated by TAVI. The primary endpoint was to evaluate death rates from any cause at two years., Results: The study included 160 consecutive patients with a mean age of 87 ± 2.1 years (range from 85 to 94 years) and a mean logistic EuroSCORE of 18.8% ± 11.2% with 57 (35.6%) patients scoring ≥ 20%. Procedural success rate was 97.5%, with 25 (15.6%) patients experiencing acute complications with major bleeding (the most frequent). Global mortality rate during hospitalization was 8.8% (n = 14) and 30-day mortality rate was 10% (n = 16). Median follow up period was 252.24 ± 232.17 days. During the follow-up period, 28 (17.5%) patients died (17 of them due to cardiac causes). The estimated two year overall and cardiac survival rates using the Kaplan-Meier method were 71% and 86.4%, respectively. Cox proportional hazard regression showed that the variable EuroSCORE ≥ 20 was the unique variable associated with overall mortality., Conclusions: TAVI is safe and effective in a selected population of very elderly patients. Our findings support the adoption of this new procedure in this complex group of patients.

Objective: Our aim in this study was to provide novel information on the molecular mechanisms playing a major role in the unwanted platelet activation associated with ST-elevation myocardial infarction (STEMI)., Methods and Results: We compared the platelet proteome of 11 STEMI patients to a matched control group of 15 stable chronic ischemic cardiopathy patients. In addition, we did a prospective study to follow the STEMI patients over time. Proteins were separated by high-resolution 2D gel electrophoresis, identified by mass spectrometry, and validated by Western blotting. Platelets from STEMI patients on admission displayed 56 protein spot differences (corresponding to 42 unique genes) compared with the control group. The number of differences decreased with time during the patients' follow-up. Interestingly, the adapter protein CrkL and the active form of Src (phosphorylated in Tyr418) were found to be upregulated in platelets from STEMI patients. Major signaling pathways related to the proteins identified include integrin, integrin-linked kinase, and glycoprotein VI (GPVI) signaling. Interestingly, a study on an independent cohort of patients showed a higher degree of activation of GPVI signaling in STEMI patients., Conclusions: CrkL, the active form of Src, and GPVI signaling are upregulated in platelets from STEMI patients.

Introduction and Objectives: To validate the axillary approach as a safe and efficient option for the transcatheter aortic valve implantation in patients who have contraindication for femoral approach at three Spanish hospitals., Methods: We included patients with severe symptomatic aortic stenosis at very high or prohibitive surgical risk, selected by a multidisciplinary team, for transcatheter aortic valve implantation, and had contraindication to the femoral approach., Results: We included 19 of 186 (10.5%) patients, who were implanted a percutaneous aortic valve, between November 2008 and March 2010. The mean age was 78.3 (standard deviation [SD]±8.65) years and 73.7% were males. The mean logistic EuroSCORE was 28.7% (SD±16.3%). The procedural success rate was 100%. After the procedure the maximum transvalve gradient decreased from 81.7 mmHg (SD±21.5) to 15.8 mmHg (SD±5.5), and no patient presented residual aortic regurgitation >2. The all-cause mortality, with a mean follow-up time of 9.2 (SD±3.2) months was 10.5%, and the in-hospital and 30-day mortality rates were 0%. The global incidence of major complications due to the procedure was 15.7%. Definitive pacemaker implantation was carried out for atrioventricular block in 8 patients (44.4%)., Conclusions: The axillary approach for transcatheter aortic valve implantation using the CoreValve(®) and contraindication to the femoral approach is safe and efficient for selected patients, with excellent results in terms of success implantation and in hospital and 30-day mortality., (Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Introduction and Objectives: The high level of metabolic activity present in visceral adipose tissue is associated with the development of atherothrombosis. Subcutaneous adipose tissue secretes larger quantities of the adipocytokines leptin and adiponectin than visceral adipose tissue. Epicardial adipose tissue secretes inflammatory mediators, and the resulting proinflammatory activity is greater than that associated with subcutaneous adipose tissue. The aim of this study was to compare adiponectin and leptin expression in human epicardial and subcutaneous adipose tissue., Methods: Samples of both epicardial and subcutaneous adipose tissue were taken from 46 patients who were undergoing heart surgery, coronary artery bypass surgery, or aortic or mitral valve replacement. Levels of protein and gene expression of leptin and adiponectin were assessed immunohistochemically and by RT-PCR, respectively. Levels of mRNA expression in the 2 adipose tissue types were compared by real-time quantitative PCR., Results: Significant differences were found between adiponectin and leptin mRNA expression in epicardial and subcutaneous adipose tissue, with epicardial adipose tissue exhibiting lower levels of adiponectin and leptin expression. Moreover, adiponectin and leptin mRNA expression in epicardial adipose tissue was higher in women than men., Conclusions: Adiponectin and leptin expression is lower in epicardial than in subcutaneous adipose tissue. Moreover, there are differences in adiponectin and leptin expression in epicardial adipose tissue between women and men.