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Abstract Background Diabetes mellitus (DM) is associated with premature atherosclerotic disease, coronary artery disease (CAD) and chronic heart failure (HF), leading to increased morbidity and mortality. Sodium-Glucose Co-transporter 2 Inhibitors (SGLT2i) exhibit cardioprotective benefits beyond glucose lowering, reducing the risk of major cardiovascular events (MACE) and HF hospitalizations in patients with DM and CAD. Endothelial progenitor cells (EPCs) are bone marrow-derived cells involved in vascular repair, mobilized in response to vascular injury. The number and function of circulating EPCs (cEPCs) are negatively affected by cardiovascular risk factors, including DM. This study aimed to examine the response of cEPCs to SGLT2i treatment in DM patients with stable CAD. Methods A prospective single-center study included patients with DM and stable CAD who were started on an SGLT2i (empagliflozin). Peripheral blood samples were collected at baseline, 1 month, and 3 months to evaluate cEPC levels and function by flow cytometry, immunohistochemistry and MTT assays. Results Eighteen patients were included in the study (median age 73, (IQR 69, 77) years, 67% male). After 1 month of treatment with empagliflozin, there was no significant change in cEPCs level or function. However, following 3 months of treatment, a significant increase was observed both in cell levels (CD34(+)/VEGFR-2(+): from 0.49% (IQR 0.32, 0.64) to 1.58% (IQR 0.93, 1.82), p = 0.0006; CD133(+)/VEGFR-2(+): from 0.38% (IQR 0.27, 0.6) to 0.82% (IQR 0.7, 1.95), p = 0.0001) and in cell function (from 0.25 CFUs (IQR 0, 0.5) at baseline, to 2 CFUs (IQR 1, 2) at 3 months, p = 0.0012). Conclusions Empagliflozin treatment in patients with DM and stable CAD increases cEPC levels and function, implying a cardioprotective mechanism. These findings highlight the potential of SGLT2i in treating cardiovascular diseases, warranting further research to explore these effects and their long-term implications. Graphical Abstract

Introduction: Transcatheter aortic valve implantation (TAVI) has emerged as a common and effective treatment for patients with severe aortic stenosis. Changes in systemic blood pressure after TAVI have been described, yet their prognostic value is not established. Thus, we aimed to examine the association of the periprocedural changes in systolic blood pressure (SBP) and in pulse pressure on clinical outcomes after the procedure. Methods: A retrospective study of consecutive patients who underwent TAVI procedure in our medical center. We assessed the effect of the periprocedural changes in blood pressure measurements on mortality, acute myocardial infarction, stroke and hospitalizations at 1 year and on the combined outcome of death, myocardial infarction, and stroke 1 year following the procedure. Results: Our cohort included 455 patients (44% males). Of them, 343 patients (75.4%) had raised SBP immediately after the procedure. Patients with raised SBP had a significantly higher rate of the 1-year composite outcome, compared to patients who did not have a raise in SBP following the procedure (43 [13%] vs. 6 [5.4%], respectively, p = 0.033). After adjustment for age and sex, the postprocedural increase in SBP was significantly associated with the composite outcome, with a hazard ratio of 2.42, 95% CI: 1.03–5.7. Conclusion: An immediate increase in SBP after TAVI is associated with worse 1-year clinical cardiovascular outcomes.

Background Cerebrovascular events remain one of the most devastating complications of transcatheter aortic valve implantation (TAVI). Data from real‐world contemporary cohorts on longitudinal trends and outcomes remain limited. The aim of this study was to assess incidence, temporal trends, predictors, and outcomes of cerebrovascular events following transfemoral TAVI. Methods and Results The CENTER2 (Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Implantation With Balloon‐Expandable Valves Versus Self‐Expandable Valves 2) study includes patients undergoing TAVI between 2007 and 2022. The database contains pooled patient‐level data from 10 clinical studies. A total of 24 305 patients underwent transfemoral TAVI (mean age 81.5±6.7 years, 56% women, median Society of Thoracic Surgeon Predicted Risk of Mortality 4.9% [3.1%–8.5%]). Of these patients, 2.2% (n=534) experienced stroke in the first 30 days after TAVI, and 40 (0.4%) had a transient ischemic attack. Stroke rates remained stable during the treatment period (2007–2010: 2.1%, 2011–2014: 2.5%, 2015–2018: 2.1%, 2019–2022: 2.1%; Ptrend=0.28). Moreover, 30‐day cerebrovascular event rates were similar across Society of Thoracic Surgeon Predicted Risk of Mortality risk categories: 2.1% in low‐risk, 2.6% in intermediate‐risk, and 2.5% in high‐risk patients (P=0.21). Mortality was higher in patients with 30‐day stroke than without at 30 days (20.3% versus 4.7%; odds ratio, 5.1 [95% CI, 4.1–6.5]; P

Rationale & Objective: Kidney function can be adversely affected by significant tricuspid regurgitation (TR) owing to effects on cardiac output and systemic venous congestion. However, the impact of significant TR on short- and long-term kidney function following a kidney transplant remains uncertain. Study Design: Retrospective observational cohort. Setting & Participants: Kidney transplant recipients from a single center between 2016 and 2019. Exposure: Significant TR, defined by at least moderate regurgitation, on echocardiogram before kidney transplantation. Outcomes: Primary end points included the estimated glomerular filtration rate (eGFR) at the following 3 time points: 2 weeks, 3 months, and 1 year after transplantation. Secondary end points included major adverse cardiac events including nonfatal myocardial infarction, all-cause mortality, and hospitalization owing to cardiovascular disease. Analytical Approach: Propensity score matching was performed in 1:3 ratio between patients treated with significant TR and controls, within a caliper 0.05 standard deviation of the propensity score, to analyze for the primary end point. Results: Among 557 kidney transplant recipients, 26 (5%) exhibited significant TR pretransplantation. According to propensity score matching analysis, with 1:3 ratio between 24 patients with significant TR and 72 controls, the presence of significant TR was associated with a lower eGFR posttransplantation. Specifically, the mean eGFR was 41.2 mL/min/1.73 m2 compared to 53.3 mL/min/1.73 m2 at 2 weeks (P

Abstract Aims This study aimed to characterize the final diagnosis and prognosis of patients with grade 1 myocardial scintigraphy uptake, which is an unequivocal result for the diagnosis of transthyretin cardiac amyloidosis (ATTR‐CA) requiring further invasive investigation with tissue biopsy. Methods and results We retrospectively compared the clinical and imaging parameters of patients suspected for ATTR‐CA (based on clinical and echocardiographic parameters) with grade 1 vs. grades 2/3 technetium pyrophosphate uptake on cardiac scintigraphy. Prospectively, grade 1 patients underwent re‐evaluation for ATTR‐CA at long term. Of the 132 ATTR‐CA suspected patients, 89 (67%) were diagnosed as grade 1 and 43 (33%) as grades 2/3 uptake. Grade 1 vs. grades 2/3 patients were younger and female predominant with lower biomarker levels and left ventricular mass. Based on available imaging and pathology findings, only 6 out of the 89 patients with grade 1 uptake (7%) were finally diagnosed with light‐chain cardiac amyloidosis, whereas no patient was diagnosed with ATTR‐CA. At 2 [interquartile range (IQR) 0.75, 3.25] years of follow‐up, the survival of patients with grade 1 vs. grades 2/3 uptake was significantly better [hazard ratio 0.271 (95% confidence interval 0.130 to 0.563, P = 0.0005)]. Prospectively, 30 patients with grade 1 uptake were re‐evaluated at a median follow‐up of 3.2 (IQR 2.2, 3.9) years. Their New York Heart Association class, biomarker levels, and echocardiography findings remained stable. No patient (0/25) demonstrated grades 2/3 uptake at repeated long‐term scintigraphy. Conclusions Patients with suspected ATTR‐CA and a grade 1 scintigraphy uptake demonstrate a stable clinical, laboratory, imaging, and scintigraphy phenotype along with a benign survival profile at long‐term follow‐up. Larger studies should define the optimal evaluation strategy in this population.

A 17-year-old athlete was initially diagnosed with presumed hypertrophic cardiomyopathy, marked by deep inferolateral T-wave inversions and mild anteroseptal hypertrophy on electrocardiogram and imaging studies. Remarkably, 6 years later, following detraining, all diagnostic signs completely resolved. This case underscores the significance of vigilant athlete follow-up.

Background Patients treated with percutaneous coronary intervention are often considered to be at a high bleeding risk (HBR). Drug‐eluting stents have been shown to be superior to bare‐metal stents in patients with HBR, even when patients were given abbreviated periods of dual antiplatelet therapy (DAPT). Short DAPT has not been evaluated with the EluNIR ridaforolimus‐eluting stent. The aim of this study was to evaluate the safety and efficacy of a shortened period of DAPT following implantation of the ridaforolimus‐eluting stent in patients with HBR. Methods and Results This was a prospective, multicenter, binational, single‐arm, open‐label trial. Patients were defined as HBR according to the LEADERS‐FREE (Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug‐Coated Stent versus the Gazelle Bare‐Metal Stent in Patients at High Bleeding Risk) trial criteria. After percutaneous coronary intervention, DAPT was given for 1 month to patients presenting with stable angina. In patients presenting with an acute coronary syndrome, DAPT was given for 1 to 3 months, at the investigator's discretion. The primary end point was a composite of cardiac death, myocardial infarction, or stent thrombosis up to 1 year (Academic Research Consortium definite and probable). Three hundred fifteen patients undergoing percutaneous coronary intervention were enrolled, and 56.4% presented with acute coronary syndrome; 33.7% were receiving oral anticoagulation. At 1 year, the primary end point occurred in 15 patients (4.9%), meeting the prespecified performance goal of 14.1% (P

BackgroundThis study aims to compare valve durability between transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR).MethodsWe conducted a systematic review and meta-analysis using data from randomized controlled trials (RCTs). The primary outcome was structural valve deterioration (SVD). Secondary outcomes were bioprosthetic valve failure, reintervention, effective orifice area (EOA), mean pressure gradient, and moderate–severe aortic regurgitation (AR, transvalvular and/or paravalvular).ResultsTwenty-five publications from seven RCTs consisting of 7,970 patients were included in the analysis with follow-up ranges of 2–8 years. No significant difference was found between the two groups with regard to SVD [odds ratio (OR) 0.72; 95% CI: 0.25–2.12]. The TAVI group was reported to exhibit a statistically significant higher risk of reintervention (OR 2.03; 95% CI: 1.34–3.05) and a moderate–severe AR (OR 6.54; 95% CI: 3.92–10.91) compared with the SAVR group. A trend toward lower mean pressure gradient in the TAVI group [(mean difference (MD) −1.61; 95% CI: −3.5 to 0.28)] and significant higher EOA (MD 0.20; 95% CI: 0.08–0.31) was noted.ConclusionThe present data indicate that TAVI provides a comparable risk of SVD with favorable hemodynamic profile compared with SAVR. However, the higher risk of significant AR and reintervention was demonstrated.Systematic Review RegistrationPROSPERO (CRD42022363060).

Abstract Background Diabetes Mellitus (DM) affects a third of patients with symptomatic severe aortic valve stenosis undergoing transcatheter aortic valve implantation (TAVI). DM is a well-known risk factor for cardiac surgery, but its prognostic impact in TAVI patients remains controversial. This study aimed to evaluate outcomes in diabetic patients undergoing TAVI. Methods This multicentre registry includes data of > 12,000 patients undergoing transfemoral TAVI. We assessed baseline patient characteristics and clinical outcomes in patients with DM and without DM. Clinical outcomes were defined by the second valve academic research consortium. Propensity score matching was applied to minimize potential confounding. Results Of the 11,440 patients included, 31% (n = 3550) had DM and 69% (n = 7890) did not have DM. Diabetic patients were younger but had an overall worse cardiovascular risk profile than non-diabetic patients. All-cause mortality rates were comparable at 30 days (4.5% vs. 4.9%, RR 0.9, 95%CI 0.8–1.1, p = 0.43) and at one year (17.5% vs. 17.4%, RR 1.0, 95%CI 0.9–1.1, p = 0.86) in the unmatched population. Propensity score matching obtained 3281 patient-pairs. Also in the matched population, mortality rates were comparable at 30 days (4.7% vs. 4.3%, RR 1.1, 95%CI 0.9–1.4, p = 0.38) and one year (17.3% vs. 16.2%, RR 1.1, 95%CI 0.9–1.2, p = 0.37). Other clinical outcomes including stroke, major bleeding, myocardial infarction and permanent pacemaker implantation, were comparable between patients with DM and without DM. Insulin treated diabetics (n = 314) showed a trend to higher mortality compared with non-insulin treated diabetics (n = 701, Hazard Ratio 1.5, 95%CI 0.9–2.3, p = 0.08). EuroSCORE II was the most accurate risk score and underestimated 30-day mortality with an observed-expected ratio of 1.15 in DM patients, STS-PROM overestimated actual mortality with a ratio of 0.77 and Logistic EuroSCORE with 0.35. Conclusion DM was not associated with mortality during the first year after TAVI. DM patients undergoing TAVI had low rates of mortality and other adverse clinical outcomes, comparable to non-DM TAVI patients. Our results underscore the safety of TAVI treatment in DM patients. Trial registration The study is registered at clinicaltrials.gov (NCT03588247).

Background Little is known about the impact of transcatheter mitral valve edge‐to‐edge repair on changes in left ventricular ejection fraction (LVEF) and the effect of an acute reduction in LVEF on prognosis. We aimed to assess changes in LVEF after transcatheter mitral valve edge‐to‐edge repair for both primary and secondary mitral regurgitation (PMR and SMR, respectively), identify rates and predictors of LVEF reduction, and estimate its impact on prognosis. Methods and Results In this international multicenter registry, patients with both PMR and SMR undergoing transcatheter mitral valve edge‐to‐edge repair were included. We assessed rates of acute LVEF reduction (LVEFR), defined as an acute relative decrease of >15% in LVEF, its impact on all‐cause mortality, major adverse cardiac event (composite end point of all‐cause death, mitral valve surgery, and residual mitral regurgitation grade ≥2), and LVEF at 12 months, as well as predictors for LVEFR. Of 2534 patients included (727 with PMR, and 1807 with SMR), 469 (18.5%) developed LVEFR. Patients with PMR were older (79.0±9.2 versus 71.8±8.9 years; P

Background Various hemodynamic changes occur following transcatheter aortic valve implantation (TAVI) that may impact therapeutic decisions. NICaS is a noninvasive bioimpedance monitoring system aimed at hemodynamic assessment. We used the NICaS system in patients with severe aortic stenosis (AS) to evaluate short‐term hemodynamic changes after TAVI. Methods and Results We performed hemodynamic analysis using NICaS on 97 patients with severe AS who underwent TAVI using either self‐expandable (68%) or balloon‐expandable (32%) valves. Patients were more often women (54%) and had multiple comorbidities including hypertension (83%), coronary artery disease (46%), and diabetes (37%). NICaS was performed at several time points—before TAVI, soon after TAVI, at hospital discharge, and during follow‐up. Compared with baseline NICaS measurements, we observed a significant increase in systolic blood pressure and total peripheral resistance (systolic blood pressure 132±21 mm Hg at baseline versus 147±23 mm Hg after TAVI, P

Abstract Background Despite increased recognition, frailty remains a significant public health challenge. Objective we aimed to assess the role of education and income, as well as neighborhood socioeconomic status, on physical activity and subsequent frailty in older adults. Methods Using a population-based cohort of older adults, this study examined the relationship between socioeconomic status (SES) factors, physical activity and frailty. The study included 1,799 participants (mean [SD], 74.6 (6.2), 53.3% female) from the "National Health and Nutrition Survey of Older Adults Aged 65 and Over in Israel", conducted in 2005–2006. A follow-up interview was performed 12–14 years later in a subgroup of 601 subjects (mean [SD], age 84[4]; 56% women). Self-reported leisure-time physical activity (LTPA) was measured at both baseline and follow-up. SES measures were assessed at baseline. Frailty was measured at follow-up, using the Fried's Phenotype Model. Results All SES measures were strongly and positively associated with LTPA (all p

Abstract Aims To assess the 6 months immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccine in a population of heart transplanted (HTx) recipients and left ventricular assist device (LVAD)‐supported patients. Methods and results A prospective single‐centre cohort study of HTx recipients and LVAD‐supported patients who received a two‐dose SARSCoV‐2 mRNA vaccine (BNT162b2, Pfizer‐BioNTech). Whole blood for anti‐spike IgG (S‐IgG) antibodies were drawn at 6 months after the first vaccine dose. S‐IgG data at 6 weeks were available for a subgroup of HTx recipients. S‐IgG ≥ 50 AU/mL were interpreted positive. The cohort included 53 HTx recipients and 18 LVAD‐supported patients. The median time from HTx or LVAD implantation to the 1st vaccine dose was 90 (IQR 30, 172) months and 22 (IQR 6, 78) months, respectively. The seropositivity rates of S‐IgG antibodies and their titre levels in HTx recipients and LVAD‐supported patients were 45% and 83% respectively, (P = 0.006), and 35 (IQR 7, 306) AU/mL and 311 (IQR 86, 774) AU/mL, respectively, (P = 0.006). Reduced SARSCoV‐2 vaccine immunogenicity in HTx recipients was associated with older age [odds ratio (OR) 0.917 confidence interval (CI 0.871, 0.966), P = 0.011] and with the use of anti‐metabolites‐based immunosuppressive regimens [OR 0.224 (CI 0.065, 0.777), P = 0.018]. mTOR inhibitors were associated with higher immunogenicity [OR 3.1 (CI 1.01, 9.65), P = 0.048]. Out of 13 HTx recipients who were S‐IgG seropositive at 6 weeks after the first vaccine dose, 85% remained S‐IgG seropositive at 6 month follow‐up. Conclusions At 6 months post‐vaccination, S‐IgG immunogenicity in HTx recipients is low, particularly in older HTx recipients and in those treated with anti‐metabolites drugs.

Abstract Background Right heart catheterization (RHC) and echocardiography are both routinely used for pulmonary artery systolic pressure (PASP) assessment in lung transplantation (LT) candidates, although this is not mandated by current guidelines. We aimed to explore the performance of echocardiographic PASP as an indicator of pulmonary hypertension in LT candidates, in order to assess the necessity of RHC. Methods From a retrospective registry of 393 LT candidates undergoing RHC and echocardiography during 2015–2019, patients were assessed for the presence of pulmonary hypertension (PH), defined as mean pulmonary artery pressure (mPAP) above 20 mmHg, according to two methods—echocardiography and RHC. The primary outcome was the correlation between the PASP estimated by echocardiography to that measured by RHC. Secondary outcomes were the prediction value of the echocardiographic evaluation and its accuracy. Results The mean value of PASP estimated by echocardiography was 49.5 ± 20.0 mmHg, compared to 42.5 ± 18.0 mmHg measured by RHC. The correlation between the two measurements was moderate (Pearson’s correlation: r = 0.609, p

To the best of our knowledge, this is the first published report of anti-immunoglobulin-like transcript 3 (ILT3)-induced myocarditis. A 48-year old female patient with refractory acute myeloid leukemia who was given a single dose of anti-ILT3 monotherapy presented with fever, hypotension, chest pain, and elevated cardiac biomarkers. Systolic bi-ventricular function was in normal limits. The patient was promptly treated with pulse dose steroids with a rapid hemodynamic and clinical improvement and declining levels of cardiac biomarkers. The diagnosis of acute myocarditis was confirmed using cardiac magnetic resonance imaging applying the revised Lake Lewis criteria. While larger-scale data are needed in order to assess the incidence, management and prognosis of anti-ILT-3 induced myocarditis, we believe a high level of suspicion for adverse non-target cardiac effects is required in patients receiving this novel class of drugs.

BackgroundThe link between thyroid dysfunction and cardiovascular disease is well established. Hypothyroidism has been significantly associated with increased risk of dyslipidemia, atherosclerosis and heart failure. However, little is known regarding its effect on patients undergoing percutaneous coronary intervention (PCI).AimThe aim of study was to examine the impact of concomitant hypothyroidism on mortality and major adverse cardiac event (MACE) in patients undergoing PCI.MethodsThe Rabin Medical Center PCI registry includes all consecutive patients who have undergone PCI between 2004 and 2020. We identified patients with prior diagnosis of hypothyroidism, and compared rates of mortality and MACE (comprising death, myocardial infarction, target vessel revascularization and/or coronary bypass surgery).ResultsAmong 28,274 patients, 1,922 (6.8%) were found to have hypothryoidism. These patients were older (70.3 ± 10.4 vs. 66.0 ± 11.8 y.o, P < 0.001) and more likely to be women (34.2% vs. 26.1%, P < 0.001). They had a higher prevalence of atrial fibrillation (10.8% vs. 7.7%, P < 0.001), chronic renal dysfunction (25.1% vs. 18.7%, P = 0.04) and dementia (2.9% vs. 1.8%, P = 0.004). PCI was performed on ACS setting in 52–54% of patients in both groups (p = 0.569). Unadjusted 5-year rates of all-cause mortality (26.9% vs. 20.3%, P < 0.001) and MACE (40.3% vs. 29.4%, P < 0.001) were higher for hypothyroid patients. A propensity match score was able to form 672 matched pairs of HT and control patients, showing similar results. Moreover, following multivariate analysis, TSH as a continuous parameter was associated with a higher risk of mortality and MACE (HR, 1.06 per additional 1 mIU/L; CI, 1.02–1.11; P < 0.001 and HR, 1.07; CI, 1.02–1.12; P < 0.001, respectively) at 5-year follow up.ConclusionIn our study, hypothyroidism confers worse outcomes in patients undergoing PCI. Further research is needed to establish effective ways to mitigate this augmented risk.

IntroductionVaccination-associated myocarditis was reported following COVID-19 vaccine initially among persons aged 16 or older and recently among adolescents aged 12–15.ObjectivesTo describe the clinical and cardiac magnetic resonance (CMR) characteristics of adolescents aged 12–15 with myocarditis following the administration of the BNT162b2 mRNA COVID-19 vaccine.MethodsCMR of adolescents (age 12–15) with a clinical diagnosis of myocarditis within 42 days following the first COVID-19 vaccine were analyzed.ResultsA total of 182,605 adolescent were vaccinated, out of which 9 were diagnosed with clinically adjudicated myocarditis while CMR was performed in 5/9 patients (56%). Median age was 15 years (range 13–15), 4/5 (80%) males. All the patients we previously healthy. The ECG upon presentation was abnormal in 3/5 (60%) of patients. All cases were classified as clinically mild and no patient required inotropes or mechanical circulatory support treatment. The median follow-up time, for the 5-included patients, was 206 (IQR 192–229, range 179–233) days. During the follow-up, no re-admissions, deaths, or any other cardiac events have occurred.The median time between the diagnosis to the CMR was 104 days (range 27–149). The median left ventricular ejection fraction was within normal range 65% (range 62–69). Native T1 was available in four patients, the local T1 value was increased in three of them. T2 values were available in two patients and were all within normal range. The median late gadolinium enhancement (LGE) was 2% (range 0–6%) with inferolateral wall being the most common location (3/5). The patterns of the LGE were as following: (i) mid-wall in 3 patients; (ii) epicardial in 1-patient. LGE in the pericardium was present in 2/5 patients with pericardial effusion present in 4/5 patients with a median diameter of 4 mm (range 3–5 mm) at end-systole.ConclusionsCMR findings and clinical course of adolescents with COVID-19 vaccination associated myocarditis, are similar to those of older patients, being relatively mild and potentially implying favorable outcomes.

Abstract Aims This study aimed to evaluate the different health‐related quality of life (HR‐QoL) aspects in patients with both short‐term and long‐term duration LVAD support at pre‐specified time intervals. Methods and results We performed a single‐centre HR‐QoL analysis of short‐term and long‐term LVAD‐supported patients using the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ‐12) and the Changes in Sexual Functioning Questionnaire along with a survey to evaluate patients' social and driving routines. Data were collected at baseline and at 6 or 12 month follow‐up. Included were 46 patients with a median time from LVAD implantation of 1.1 [inter‐quartile range (IQR) 0.5, 2.6] years. The median KCCQ‐12 summary score was 56 (IQR 29, 74) with most favourable scores in the symptom frequency domain [75 (IQR 50, 92)] and worse scores in the physical limitation [42 (IQR 25, 75)] and QoL [44 (IQR 25, 75)] domains. No significant changes were apparent during study follow‐up [KCCQ‐12 summary score 56 (IQR 35, 80)], and no significant correlation between the KCCQ‐12 summary score and ventricular assist device‐support duration was detected (r = −0.036, P = 0.812). Sexual dysfunction was noted across all domains with a cumulative score of 31 (IQR 22, 42). Seventy‐six per cent of patients resumed driving after LVAD implantation, and 43% of patients reported they socialize with family and friends more frequently since surgery. Conclusions Short‐term and long‐term LVAD‐supported patients had impaired HR‐QoL and sexual function at baseline and at follow‐up yet reported an improvement in social interactions and independency. A broader spectrum of patient's reported HR‐QoL measures should be integrated into the pre‐LVAD implantation assessment and preparation.

Abstract Whole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.

Objective: This study sought to investigate the effect of body mass index on outcomes in patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation. Methods: A total of 12,381 patients undergoing transfemoral transcatheter aortic valve implantation were divided into body mass index categories: underweight (30 kg/m2). Primary endpoints were differences in 30-day and 1-year all-cause mortality. Secondary endpoints included all other clinical endpoints such as stroke. Univariate and multivariate odds ratios were calculated using logistic and cox regression analyses. Results: Two percent (n = 205) of patients were underweight, 29% (n = 3564) were normal weight, 44% (n = 5460) were overweight, and 25% (n = 3152) were obese. Thirty-day mortality was lower in overweight (5.3%, odds ratio, 0.73; 95% confidence interval, 0.61-0.88; P = .001) and obese patients (5.2%, odds ratio, 0.74; 95% confidence interval, 0.60-0.92; P = .006), but higher in underweight (9.8%, odds ratio, 1.51; 95% confidence interval, 0.92-2.47; P = .010) as compared to normal weight patients (6.9%). After multivariate adjustment, 30-day mortality was not significantly different across body mass index categories. However, 1-year mortality was higher in underweight patients (hazard ratio, 1.52; 95% confidence interval, 1.10-2.09; P = .011). Stroke rates were comparable between body mass index groups. Conclusions: For overweight and obese patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation, there was no 30-day difference in mortality compared with patients with normal weight. However, underweight patients showed higher rates of 1-year mortality after transcatheter aortic valve implantation.

AimsNon-invasive coronary assessment using single-photon emission computerized tomography (SPECT) testing for potential cardiac ischemia is an essential part of the evaluation of kidney transplant candidates. We aimed to examine the prognostic value of preoperative SPECT test results in kidney transplanted patients.Methods and resultsWe retrospectively analyzed the pre-surgical nuclear SPECT test results in a registry of kidney transplanted patients. Follow-up at 1 month and 1 year recorded major adverse cardiac events (MACE) including non-fatal myocardial infarction, all-cause mortality and hospitalization due to cardiovascular disease following the renal transplantation. Of 577 patients available for analysis, 408 (70.9%) patients underwent nuclear SPECT test pre-transplant and 83 (20.3%) had abnormal results with either evidence of ischemia or infarct. A significantly higher incidence of post-operative MACE at 1 month was evident among patients with abnormal SPECT test compared to patients with no evidence of ischemia (10.8 vs. 4.3% respectively; P = 0.019). Differences were mostly derived from significantly increased rates of myocardial infarction events (8.4 vs. 1.8%; P = 0.002). Yet, MACE rate was not statistically different at 1 year (20.5 vs. 13.1%; P = 0.88). Importantly, the prognostic impact of an abnormal SPECT was significantly attenuated for all outcomes following multivariable adjusting for conventional cardiovascular risk factors and coronary revascularization.ConclusionPre-surgical cardiac risk assessment of kidney transplant candidates with nuclear SPECT test was found to be predictive of post-operative MACE, yet apparently, its prognostic value was significantly attenuated when adjusted for cardiac risk factors.

BackgroundAccumulated experience combined with technological advancements in percutaneous coronary interventions (PCI) over the past four decades, has led to a gradual increase in PCI utilization and complexity. We aimed to investigate the temporal trends in PCI complexity and the outcomes of complex PCI (C-PCI) in our institution.MethodsWe analyzed 20,301 consecutive PCI procedures performed over a 12-year period. C-PCI was defined as a procedure involving at least one of the following: Chronic total occlusion (CTO), left main (LM), bifurcation or saphenous vein graft (SVG) PCI. Four periods of 3-year time intervals were defined (2008–10, 2011–2013, 2014–2016, 2017–2019), and temporal trends in the rate and outcomes of C-PCI within these intervals were studied. Endpoints included mortality and major adverse cardiac events [MACE: death, acute myocardial infarction (MI), and target vessel revascularization (TVR)] at 1 year.ResultsA total of 5,647 (27.8%) C-PCI procedures were performed. The rate of C-PCI has risen significantly since 2,017 (31.2%, p < 0.01), driven mainly by bifurcation and LM interventions (p < 0.01). At 1-year, rates of death, acute MI, TVR and MACE, were all significantly higher in the C-PCI group (8.8 vs. 5.1%, 5.6 vs. 4.5%, 5.5 vs. 4.0%, 17.2 vs. 12.2%, p < 0.001 for all, respectively), as compared to the non-complex group. C-PCI preformed in the latter half of the study period (2014–2019) were associated with improved 1-year TVR (4.4% and 4.8% vs. 6.7% and 7.1%, p = 0.01, respectively) and MACE (13.8% and 13.5% vs. 17.3% and 18.2%, p = 0.001, respectively) rates compared to the earlier period (2007–2013). Death rate had not significantly declined with time.ConclusionIn the current cohort, we have detected a temporal increase in PCI complexity coupled with improved 1-year clinical outcomes in C-PCI.

Abstract Background Diabetic and obese patients are at higher risk of severe disease and cardiac injury in corona virus 2 (SARS-CoV-2) infections. Cellular entry of SARS-CoV-2 is mainly via the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in normal hearts. There is a disagreement regarding the effect of factors such as obesity and diabetes on ACE2 expression in the human heart and whether treatment with renin–angiotensin system inhibitors or anti-diabetic medications increases ACE2 expression and subsequently the susceptibility to infection. We designed this study to elucidate factors that control ACE2 expression in human serum, human heart biopsies, and mice. Methods Right atrial appendage biopsies were collected from 79 patients that underwent coronary artery bypass graft (CABG) surgery. We investigated the alteration in ACE2 mRNA and protein expression in heart tissue and serum. ACE2 expression was compared with clinical risk factors: diabetes, obesity and different anti-hypertensive or anti-diabetic therapies. WT or db/db mice were infused with Angiotensin II (ATII), treated with different anti-diabetic drugs (Metformin, GLP1A and SGLT2i) were also tested. Results ACE2 gene expression was increased in diabetic hearts compared to non-diabetic hearts and was positively correlated with glycosylated hemoglobin (HbA1c), body mass index (BMI), and activation of the renin angiotensin system (RAS), and negatively correlated with ejection fraction. ACE2 was not differentially expressed in patients who were on angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) prior to the operation. We found no correlation between plasma free ACE2 and cardiac tissue ACE2 expression. Transmembrane serine protease 2 (TMPRSS2), metalloprotease ADAM10 and ADAM17 that facilitate viral-ACE2 complex entry and degradation were increased in diabetic hearts. ACE2 expression in mice was increased with ATII infusion and attenuated following anti-diabetic drugs treatment. Conclusion Patients with uncontrolled diabetes or obesity with RAS activation have higher ACE2 expressions therefore are at higher risk for severe infection. Since ACEi or ARBs show no effect on ACE2 expression in the heart further support their safety.

(1) Background: The use of transcatheter aortic valve implantation (TAVI) for the treatment of severe symptomatic aortic stenosis is expanding significantly. We aimed to perform a meta-analysis comparing the safety and efficacy of TAVI versus surgical aortic valve replacement (SAVR) during the early and mid-term follow-up period. (2) Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) comparing 1- to 2-year outcomes between TAVI and SAVR. The study protocol was preregistered in PROSPERO and the results were reported according to PRISMA guidelines. (3) Results: The pooled analysis included data from eight RCTs totaling 8780 patients. TAVI was associated with a lower risk of all-cause mortality or disabling stroke (OR 0.87, 95%CI 0.77–0.99), significant bleeding (OR 0.38, 95%CI 0.25–0.59), acute kidney injury (AKI; OR 0.53, 95%CI 0.40–0.69) and atrial fibrillation (OR 0.28, 95%CI 0.19–0.43). SAVR was associated with a lower risk of major vascular complication (MVC; OR 1.99, 95%CI 1.29–3.07) as well as permanent pacemaker implantation (PPI; OR 2.28, 95%CI 1.45–3.57). (3) Conclusions: TAVI compared with SAVR during early and mid-term follow-up was associated with a lower risk of all-cause mortality or disabling stroke, significant bleeding, AKI and atrial fibrillation; however, it was associated with a higher risk of MVC and PPI.

Björk conduit failure is a common reason for reintervention after a Björk modification of the Fontan procedure. We describe a first performed in human percutaneous procedure for the treatment of a failing Björk circuit in an adult with congenital heart disease and complex anatomic features. (Level of Difficulty: Advanced.)

Abstract During the coronavirus disease 2019 (COVID‐19) pandemic, many patients refrained from inpatient medical care. For those inflicted with heart failure (HF), the risk of repeat hospitalizations is particularly high in case of infection. This presents an important opportunity for remote monitoring of haemodynamic data for these patients, in order to detect and treat accordingly. The aim of the present case is to report of the first measurements of a novel wireless left atrial pressure (LAP) monitoring system, the V‐LAP™ (Vectorious Medical Technologies, Ltd), during the COVID‐19 pandemic. The V‐LAP™ Left Atrium Monitoring systEm for Patients With Chronic sysTOlic & Diastolic Congestive heart Failure (VECTOR‐HF) is a first‐in‐man clinical study assessing the safety and feasibility of the V‐LAP™ monitoring system. Our first patient, a 59‐year‐old man with severe ischaemic cardiomyopathy (left ventricular ejection fraction −30%) was enrolled prior to the COVID‐19 outbreak. As per protocol, both the patient and the medical team were blinded to the results in the first 3 months after implantation. We were able to witness the LAP during the pandemic, as the patient remained undertreated, demonstrating a gradual increase from a mean pressure of 6.56 to 19.4 mmHg, as well as prominent V waves, before the data became available to the medical team and the patient was treated accordingly. Thereafter, pressures have returned to low values. This case demonstrated the feasibility of remote monitoring of LAP using the V‐LAP™ system, as well as the potential benefit of remote care of HF patients.

The Valve-in-Valve (ViV) technique is an emerging alternative for the treatment of bioprosthetic structural valve deterioration (SVD) in the mitral position. We report on intermediate-term outcomes of patients with symptomatic SVD in the mitral position who were treated by transcatheter mitral valve-in-valve (TM-ViV) implantation during the years 2010–2019 in our center. Three main outcomes were examined during the follow-up period: NYHA functional class, TM-ViV hemodynamic data per echocardiography, and mortality. Our cohort consisted of 49 patients (mean age 77.4 ± 10.5 years, 65.3% female). The indications for TM-ViV were mainly for regurgitant pathology (77.6%). All 49 patients were treated with a balloon-expandable device. The procedure was performed via transapical access in 17 cases (34.7%) and transfemoral vein/trans-atrial septal puncture in 32 cases (65.3%). Mean follow-up was 4.4 ± 2.0 years. 98% and 91% of patients were in NYHA I/II at 1 and 5 years, respectively. Mitral regurgitation was ≥moderate in 86.3% of patients prior to the procedure and this decreased to 0% (p < 0.001) following the procedure and was maintained over 2 years follow-up. The mean trans-mitral valve gradients decreased from pre-procedural values of 10.1 ± 5.1 mmHg to 7.0 ± 2.4 mmHg at 1 month following the procedure (p = 0.03). Mortality at 1 year was 16% (95%, CI 5–26) and 35% (95%, CI 18–49) at 5 years. ViV in the mitral position offers an effective and durable treatment option for patients with SVD at high surgical risk.

Objective Some patients following acute coronary syndrome (ACS) are at particularly increased risk for recurrent cardiovascular events. We aimed to examine temporal trends in the management and outcomes across the spectrum of these particularly high-risk patients.Design and setting A retrospective study based on the ACS Israeli survey (ACSIS) registry, a multicentre prospective national registry, taking place biennially in 25 cardiology departments in Israel. Temporal trends were examined in the early (2002–2008) and late (2010–2018) time periods.Participants Consecutive patients with ACS enrolled in the ACSIS registry were stratified according to the Thrombolysis in Myocardial Infarction Risk Score for secondary prevention (TRS2°P) to high (TRS2°p=3), very high (TRS2°p=4) or extremely high risk (TRS2°p=5–9). Patients with TRS2°p

BackgroundMyocarditis has been reported following the first two doses of Pfizer-BNT162b2 messenger RNA (mRNA) COVID-19 vaccination. Administration of a third dose (booster) of the vaccine was initiated recently in Israel.ObjectiveThe aim of this study was to describe the characteristics of patients referred for cardiac magnetic resonance (CMR) imaging with myocarditis following the booster.MethodsPatients referred for CMR imaging with a clinical diagnosis of myocarditis within 21 days following the booster, between July 13 and November 11, 2021, were analyzed.ResultsOverall, 4 patients were included, 3/4 (75%) were men, and the mean age was 27 ± 10 years. The time from booster administration to the onset of symptoms was 5.75 ± 4.8 days (range 2–14). Obstructive coronary artery disease was excluded in 3 of the patients (75%). CMR was performed 34 ± 15 days (range 8-47 days) following the 3rd vaccination. The mean left ventricular ejection fraction was 61 ± 7% (range 53–71%), and regional wall motion abnormalities were present in one of the patients. Global T1 was increased in one of the patients, while focal T1 values were increased in 3 of the patients. Global T2 was increased in one of the patients, while focal T2 values were increased in all the patients. Global ECV was increased in 3 of the patients, while focal ECV was increased in all the patients. Median late gadolinium enhancement (LGE) was 4 ± 3% (range 1–9%), with the inferolateral segment as the most common location (3 of the 4 patients). All the patients met the Updated Lake Louise Criteria.ConclusionsPatient characteristics and CMR imaging findings of myocarditis following the administration of the booster vaccine are relatively mild and consistent with those observed with the first two doses. Although larger-scale prospective studies are necessary, these initial findings are somewhat reassuring.

BackgroundTranscatheter heart valve (THV) selection for transcatheter aortic valve implantation (TAVI) is crucial to achieve procedural success. Borderline aortic annulus size (BAAS), which allows a choice between two consecutive valve sizes, is a common challenge during device selection. In the present study, we evaluated TAVI outcomes in patients with BAAS according to THV size selection.MethodsWe performed a retrospective study including patients with severe aortic stenosis (AS) and BAAS, measured by multi-detector computed tomography (MDCT), undergoing TAVI with self-expandable (SE) or balloon-expandable (BE) THV from the Israeli multi-center TAVI registry. The aim was to evaluate outcomes of TAVI, mainly paravalvular leak (PVL) and valve hemodynamics, in patients with BAAS (based on MDCT) according to THV sizing selection in between 2 valve sizes. In addition, to investigate the benefit of shifting between different THV types (BE and SE) to avoid valve size selection in BAAS.ResultsOut of 2,352 patients with MDCT measurements, 598 patients with BAAS as defined for at least one THV type were included in the study. In BAAS patients treated with SE-THV, larger THV selection was associated with lower rate of PVL, compared to smaller THV (45.3 vs. 64.5%; pv = 0.0038). Regarding BE-THV, larger valve selection was associated with lower post-procedural transvalvular gradients compared to smaller THV (mean gradient: 9.9 ± 3.7 vs. 12.5 ± 7.2 mmHg; p = 0.019). Of note, rates of mortality, left bundle branch block, permanent pacemaker implantation, stroke, annular rupture, and/or coronary occlusion did not differ between groups.ConclusionBAAS is common among patients undergoing TAVI. Selection of a larger THV in these patients is associated with lower rates of PVL and optimized THV hemodynamics with no effect on procedural complications. Additionally, shift from borderline THV to non-borderline THV modified both THV hemodynamics and post-dilatation rates.

Background: Ischemic mitral regurgitation (IMR) is a common complication of acute ST-elevation myocardial infarction (STEMI). Little is known regarding the impact of IMR over a long period of follow up.Methods: Of 3,208 consecutive STEMI patients from a prospective registry, full echocardiographic information was available for 2,985 patients between the years 2000 and 2020. We compared the two decades- 2001 to 2010 and 2011 to 2020, and assessed for the presence of IMR at baseline, 3 (range 2–6) months and 12 (range 10–14) months after the index event.Results: One thousand six hundred and sixty six patients were included in the first decade, 1,319 in the second. Mean patient age was 61.3 ± 12.3 years, 21.1% female patients in the first decade vs. 60.9 ± 12.0 years and 22.2% female in the second (p = 0.40 and p = 0.212, respectively). Rates of moderate IMR or above during the index admission were 17.2% in the first period and 9.3% in the second one (p < 0.001). After 3 months, the rate of IMR was 48.5% for those who suffered from IMR at baseline, vs. 9.5% for those without IMR at baseline (HR- 4.2, p < 0.001). Death rates for those with moderate IMR or above were 14.7% and 17.8% after 1 and 2 years, respectively, vs. 7.3 and 9.6% for those without (p < 0.001 for both). IMR was associated with 1 year mortality in multivariate analysis (HR-1.37; 1.09–2.20, p = 0.009), as well as in propensity score matched analysis (HR 1.29; CI: 1.07–1.91; p < 0.001).Conclusions: IMR is a common complication following acute STEMI, impacting prognosis. Rates of IMR have declined significantly over the years.

Background: The prognostic significance of pulmonary venous (PV) flow reversal in degenerative mitral regurgitation (dMR) is not well-established. Objective: We aimed to assess whether reversed PV flow is associated with adverse outcomes in patients with significant dMR. Methods: We retrospectively analyzed consecutive patients referred to a tertiary center for evaluation of dMR of greater than moderate degree, who had normal sinus rhythm, had a left ventricular ejection fraction of above 60%, and did not suffer from any other major valvular disorders. The primary outcome was the combined rate of all-cause mortality, mitral intervention, or new-onset atrial fibrillation (AF) at 5 years following index echocardiogram. Secondary outcomes included individual components of the primary outcome. Results: Overall, 135 patients (median age 68 (IQR, 58–74) years; 93 (68.9%) males; 89 (65.9%) with severe MR) met the inclusion criteria and were followed for 115.2 (IQR, 60.0–155.0) months. Patients with a reversed PV flow pattern (PVFP) (n = 34) more often presented with severe MR compared to those with a normal (n = 49) and non-reversed PVFP (n = 101) (RR = 2.03 and 1.59, respectively, all p < 0.001). At 5 years, they experienced the highest cumulative incidence of the primary outcome (80.2% vs. 59.2% and 67.3%, p = 0.008 and 0.018, respectively). Furthermore, a reversed PVFP was independently associated with a higher risk of the primary outcome compared to normal PVFP (HR 2.53, 95% CI 1.21–5.31, p = 0.011) and non-reversed PVFP (HR 2.14, 95% CI 1.12–4.10, p = 0.022). Conclusion: PV flow reversal is associated with a worse 5-year composite of mortality, mitral intervention, or AF in patients with significant dMR.

Background: Pre-procedural TIMI coronary flow grade in patients with ST segment elevation myocardial infarction (STEMI) is associated with adverse clinical outcomes. There have been great advances in pharmacologic and invasive treatment of STEMI patients in the current era. We aimed to assess the temporal trends in clinical outcomes according to the TIMI flow grade amongst these patients. Methods: Data of patients with STEMI from the acute coronary syndrome Israeli Survey (ACSIS) registry. A time-dependent analysis stratifying patient by TIMI flow grade 0 and TIMI flow grade 1–3 was performed. Survey years were divided to early (2008–2010) and late period (2013–2018). Clinical outcomes included in-hospital complications, 30d MACE (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1-year mortality.Results and Conclusions: Included were 2453 patients. The majority of patients had pre-procedural TIMI flow 0 (58.9% in the early period and 58.7% in the late period, P = 0.97). In-hospital complications of patients with TIMI flow 0 has significantly decreased over time (36.1% vs 26.8%, P

The Valve-in-Valve (ViV) technique is an established alternative for the treatment of structural bioprosthetic valve deterioration (SVD). Data describing the intermediate term follow up of patients treated with this approach is scarce. We report on our intermediate-term outcomes of patients with SVD in the Aortic position treated with ViV. Included were patients with symptomatic SVD in the aortic position valve who were treated by Valve in valve transcatheter aortic valve implantation (ViV-TAVI) during the years 2010-2019 in our center. Three main outcomes were examined during the follow up period: NYHA functional class, ViV-TAVI hemodynamic per echocardiography, and mortality. Our cohort consisted of 85 patients (mean age 78.8 ± 8.9 years). The indications for aortic ViV were: SVD isolated aortic stenosis in 37.6%, SVD isolated aortic regurgitation in 42.2% and combined valve pathology in 20.0%. Self-expandable and balloon-expandable devices were used in 73 (85.9%) and 12 (14.1%), respectively. Average follow up was 3.7 ± 2.4 years. 95 and 91% of patients were in NYHA functional class I/II at 1 and 5 year follow up respectively. At one year, the mean trans-aortic valve pressure was 15 ± 9 mmHg and rates of ≥ moderate aortic regurgitation were 3.7%. Mortality at one year was 8.6% (95% CI 2.3–14.4) and 31% (95% CI 16.5–42.5) at 5 years. ViV in the aortic position offers an effective and durable treatment option for patient with SVD, with low rates of all-cause mortality, excellent hemodynamic and improved functional capacity at intermediate follow up.

Objective: NOV/CCN3 is an adipocytokine recently linked to obesity, insulin resistance, and cardiometabolic dysfunction. NOV is manufactured and secreted from adipose tissue, with blood levels highly correlated with BMI. NOV levels are increased in obesity and a myriad of inflammatory diseases. Elevated NOV levels cause oxidative stress by increasing free radicals, decreasing antioxidants, and decreasing heme oxygenase (HO-1) levels, resulting in decreased vascular function. Silencing NOV in NOV knockout mice improved insulin sensitivity. We wanted to study how suppressing NOV expression in an obese animal model affected pathways and processes related to obesity, inflammation, and cardiometabolic function. This is the first study to investigate the interaction of adipose tissue-specific NOV/CCN3 and cardiometabolic function. Methods: We constructed a lentivirus containing the adiponectin-promoter-driven shNOV to examine the effect of NOV inhibition (shNOV) in adipose tissue on the heart of mice fed a high-fat diet. Mice were randomly divided into three groups (five per group): (1) lean (normal diet), (2) high-fat diet (HFD)+ sham virus, and (3) HFD + shNOV lentivirus. Blood pressure, tissue inflammation, and oxygen consumption were measured. Metabolic and mitochondrial markers were studied in fat and heart tissues. Results: Mice fed an HFD developed adipocyte hypertrophy, fibrosis, inflammation, and decreased mitochondrial respiration. Inhibiting NOV expression in the adipose tissue of obese mice by shNOV increased mitochondrial markers for biogenesis (PGC-1α, the nuclear co-activator of HO-1) and functional integrity (FIS1) and insulin signaling (AKT). The upregulation of metabolic and mitochondrial markers was also evident in the hearts of the shNOV mice with the activation of mitophagy. Using RNA arrays, we identified a subgroup of genes that highly correlated with increased adipocyte mitochondrial autophagy in shNOV-treated mice. A heat map analysis in obese mice confirmed that the suppression of NOV overrides the genetic susceptibility of adiposity and the associated detrimental metabolic changes and correlates with the restoration of anti-inflammatory, thermogenic, and mitochondrial genes. Conclusion: Our novel findings demonstrate that inhibiting NOV expression improves adipose tissue function in a positive way in cardiometabolic function by inducing mitophagy and improving mitochondrial function by the upregulation of PGC-1α, the insulin sensitivity signaling protein. Inhibiting NOV expression increases PGC-1, a key component of cardiac bioenergetics, as well as key signaling components of metabolic change, resulting in improved glucose tolerance, improved mitochondrial function, and decreased inflammation. These metabolic changes resulted in increased oxygen consumption, decreased adipocyte size, and improved cardiac metabolism and vascular function at the structural level. The crosstalk of the adipose tissue-specific deletion of NOV/CCN3 improved cardiovascular function, representing a novel therapeutic strategy for obesity-related cardiometabolic dysfunction.

Background In ST‐segment–elevation myocardial infarction, angiography‐based complete revascularization is superior to culprit‐lesion‐only percutaneous coronary intervention. Quantitative flow ratio (QFR) is a novel, noninvasive, vasodilator‐free method used to assess the hemodynamic significance of coronary stenoses. We aimed to investigate the incremental value of QFR over angiography in nonculprit lesions in patients with ST‐segment–elevation myocardial infarction undergoing angiography‐guided complete revascularization. Methods and Results This was a retrospective post hoc QFR analysis of untreated nontarget vessels (any degree of diameter stenosis [DS]) from the randomized multicenter COMFORTABLE AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST‐Elevation Myocardial Infarction) trial by assessors blinded for clinical outcomes. The primary end point was cardiac death, spontaneous nontarget vessel myocardial infarction, and clinically indicated nontarget vessel revascularization (ie, ≥70% DS by 2‐dimensional quantitative coronary angiography or ≥50% DS and ischemia) at 5 years. Of 1161 patients with ST‐segment–elevation myocardial infarction, 946 vessels in 617 patients were analyzable by QFR. At 5 years, the rate of the primary end point was significantly higher in patients with QFR ≤0.80 (n=35 patients, n=36 vessels) versus QFR >0.80 (n=582 patients, n=910 vessels) (62.9% versus 12.5%, respectively; hazard ratio [HR], 7.33 [95% CI, 4.54–11.83], P30% DS by 3‐dimensional quantitative coronary angiography. Conclusions Our study suggests incremental value of QFR over angiography‐guided percutaneous coronary intervention for nonculprit lesions among patients with ST‐segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Objective: This article describes the women population and work at a unique Women’s Health Cardiology Clinic in order to raise cardiovascular disease awareness with an emphasis on women-specific risk factors, and thus to improve women’s clinical outcomes. This expectantly will aid in opening similar centers allowing more women to get superior care. Methods: Electronic medical records of women referred to the Women’s Health Cardiology Clinic were analyzed. The statistical analysis is descriptive in nature. Women’s Health Cardiology Clinic personnel work as a multidisciplinary team, and patients receive specialized diagnostic tests and treatments. Referrals are by physicians according to traditional and women’s specific risk factors for cardiovascular disease. Results: 985 women visited the Women’s Health Cardiology Clinic, accumulating 2062 visits. Median age was 57.5 years. The majority of the women were menopausal (575 women, 58%), 62 pregnant with complications and 25 oncology patients. At least, 30% of women had diabetes/hypertension/or dyslipidemia. 72 women had a history of either cerebrovascular event or acute coronary syndrome, and 139 women had evidence of atherosclerosis. Overall, 388 women underwent endothelial function test, 40% of these women had a score indicating endothelial dysfunction. 277 women underwent a psychological intervention. Conclusion: Described here are the experiences from a multidisciplinary Women’s Health Cardiology Clinic using a gender-specific cardiovascular care approach for women geared toward improved health and wellbeing. It is of utmost importance that this report will raise women-specific cardiovascular disease risk factors awareness in order to promote women’s cardiovascular and overall health.

Aims To compare the baseline cardiovascular characteristics of immunoglobulin light-chain (AL) and amyloid transthyretin (ATTR) cardiac amyloidosis (CA) and to investigate patients’ contemporary cardiac outcomes. Methods Single-center analysis of clinical, laboratory, echocardiographic and cardiac magnetic resonance imaging (CMRi) characteristics of AL and ATTR-CA patients’ cohort (years 2013–2020). Results Included were 67 CA patients of whom 31 (46%) had AL-CA and 36 (54%) had ATTR-CA. Patients with ATTR-CA versus AL-CA were older (80 (IQR 70, 85) years versus 65 (IQR 60, 71) years, respectively, pConclusion Despite the various similarities of AL-CA and ATTR-CA, these diseases have distinct baseline cardiovascular profiles and different heart failure course, thus merit tailored-cardiac management.

BackgroundThe extent of myocardial fibrosis in patients with severe aortic stenosis might have an important prognostic value. Non-invasive imaging to quantify myocardial fibrosis by measuring extracellular volume fraction might have an important clinical utility prior to aortic valve intervention.MethodsSeventy-five consecutive patients with severe aortic stenosis, and 19 normal subjects were prospectively recruited and underwent pre- and post-contrast computed tomography for estimating myocardial extracellular volume fraction. Serum level of galectin-3 was measured and 2-dimensional echocardiography was performed to characterize the extent of cardiac damage using a recently published aortic stenosis staging classification.ResultsExtracellular volume fraction was higher in patients with aortic stenosis compared to normal subjects (40.0±11% vs. 21.6±5.6%; respectively, pConclusionIn patients with severe aortic stenosis undergoing computed tomography before aortic valve intervention, quantification of extracellular volume fraction correlated with functional status and markers of left ventricular decompensation, and predicted the 12-months composite adverse clinical outcomes. Implementation of this novel technique might aid in the risk stratification process before aortic valve interventions.

Background and Aims. Plasma levels of soluble triggering receptor expressed on myeloid cells (sTREM-1) reflect innate immune cell activation. We sought to evaluate sTREM-1 levels in patients with acute coronary syndrome (ACS) and their predictive value for disease severity and outcome. Methods. Plasma sTREM-1 levels were prospectively measured by ELISA in 121 consecutive patients with new-onset (≤24 h) chest pain at arrival to the emergency department (ED) and 73 healthy controls. Secondary endpoints were the association of plasma levels of sTREM-1 with day 30 and month 6 major adverse cardiovascular events (MACE) defined as death, ACS, stroke, and need for coronary revascularization, as well as with CAD severity. The primary endpoint of the study was the association of plasma sTREM-1 level at the time of admission to the ED with a diagnosis of ACS at day 30. Results. Fifty-nine patients (48.7%) were diagnosed with ACS and 62 (51.3%) with nonspecific chest pain (NSCP). Median plasma sTREM-1 level at admission was significantly higher in the ACS group than the NSCP group and the control group (539.4±330.3 pg/ml vs. 432.5±196.4 pg/ml vs. 230.1±85.5 pg/ml, respectively; P

Background Peripheral artery disease (PAD) is a known risk factor for adverse outcomes in patients undergoing percutaneous coronary intervention. However, in some studies PAD is not an independent risk factor. We sought to examine the independent impact of PAD on a large prospective percutaneous coronary intervention registry. Methods and Results From our single‐center prospective percutaneous coronary intervention registry, we have retrospectively analyzed 25 690 patients (years 2004–2018). We examined the influence of PAD on short‐ and long‐term outcomes using both regression and propensity‐matched analyses. Patients with documented PAD (n=1610, 6.3% of total) were older (66.7±10.8 versus 65.4±12.1, P

An accurate functional assessment of coronary artery stenosis is pivotal in the management and clinical outcomes of patients. The hemodynamic relevance of coronary artery stenoses can be assessed using coronary flow surrogates, namely fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). This review provides an overview of these indexes, their clinical relevance, as well as a review of the literature supporting their use. It also reviews novel image-based FFR (e.g. FFRangio), the evidence showing the accuracy of this technique when compared to conventional wire-based techniques, as well as the clinical implications of non-invasive coronary artery stenosis functional assessments.

BackgroundGestational diabetes mellitus (GDM) is associated with future cardiovascular morbidity and recognized as a women-specific risk factor for cardiovascular disease. The mechanisms for this association are not well established. Therefore, we aimed to evaluate the cardiovascular-related biomarkers, galectin-3 (Gal-3) and protein convertase subtilisin/kexin (PCSK) type 9, in women with GDM.MethodsBlood samples were drawn in the third trimester from 31 women diagnosed with GDM and from 35 women with normal pregnancies. Blood levels of Gal-3 and PCSK-9 were measured using a quantitative sandwich enzyme immunoassay. In addition, we measured Gal-3 levels in 24 pregnant women in the first trimester who later developed GDM and in 36 healthy controls. Continuous variables were compared using student's t-test and categorical variables by chi-square/fisher's exact tests.ResultsWe found increased levels of Gal-3 in women diagnosed with GDM compared to women without GDM (124.6±32% versus control; pv = 0.001). Furthermore, we demonstrated elevated levels of Gal-3 during the first trimester among women who later developed GDM compared with women who did not develop any gestational morbidity (125.7±32% versus control; pv = 0.004). Third-trimester levels of PCSK-9 did not differ between women with and without GDM (560±45ng/mL versus 553±33ng/mL; pv = 0.4).ConclusionsThe results suggest a possible mechanism that may link GDM to the future increased cardiovascular risk in these patients. Additionally, increased Gal-3 levels during the first trimester may suggest a new early predictor for GDM.

Background Cardiovascular disease remains a leading cause of death among women. Despite improvements in the management of patients with acute coronary syndrome (ACS), women with an ACS remain at higher risk. Methods and Results We performed a time‐dependent analysis of the management and outcomes of women admitted with ACS who enrolled in the prospective biennial ACS Israeli Surveys between 2000 and 2016. Surveys were divided into 3 time periods (2000‐2004, 2006‐2010, and 2013‐2016). Outcomes included 30‐day major adverse cardiac events (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1‐year mortality. Overall, 3518 women were admitted with an ACS. Their mean age (70±12 years) was similar among the time periods. Over the time course of the study, more women were admitted with non–ST‐elevation ACS (51.9%, 59.6%, and 66.1%, respectively; P

Abstract Background High admission blood glucose (ABG) level has been associated with a poor short-term outcome among non-diabetic patients with heart failure (HF). We aimed to investigate the association between ABG levels and long-term (10 years) mortality in patients with or without pre-existing diabetes mellitus (DM) admitted with HF. Methods We analyzed data on 1811 patients with DM and 2182 patients without pre-existing DM who were hospitalized with HF during a prospective national survey. The relationship between ABG and 10-year mortality was assessed using the Cox proportional hazard model adjusting for multiple variables. ABG was analyzed both as a categorical (200 mg/dL) and as a continuous variable. Results At 10 years of follow-up the cumulative probability of mortality was 85 and 78% among patients with DM and patients with no pre-existing DM (p 200 mg/dL had an increased mortality risk (>200 mg/dL versus 200 mg/dL is associated with increased mortality risk.