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Background: Despite advances in transcatheter aortic valve replacement (TAVR), periprocedural acute ischemic stroke remains a concern. Objectives: The aims of this study were to investigate acute ischemic stroke complicating TAVR (AISCT) and to describe the indications and outcomes of interventions to treat AISCT. Methods: An international multicenter registry was established focusing on AISCT within 30 days of TAVR. Stroke severity was assessed using the National Institutes of Health Stroke Scale. Primary outcomes were 1-year all-cause death and neurologic disability status at 90 days according to modified Rankin scale score. Results: Of 16,615 TAVR procedures, 387 patients with AISCT were included (2.3%). Rates of 1-year death were 28.9%, 35.9%, and 77.5% in patients with mild, moderate, and severe stroke, respectively (P < 0.001). Although 348 patients were managed conservatively, 39 patients (10.1%) underwent neurointervention (NI) with either mechanical thrombectomy (n = 26) or thrombolytic therapy (n = 13). In a subanalysis excluding patients with mild stroke, there was no clear 1-year survival benefit for NI compared with conservative management (47.6% vs 41.1%, respectively; P = 0.78). In a logistic regression model controlling for stroke severity, NI was associated with 2.9-fold odds (95% CI: 1.2-7.0; P = 0.016) of independent survival at 90 days. Conclusions: AISCT carries significant morbidity and mortality, which is correlated with stroke severity. The present findings suggest that neurologic disability for patients with moderate or worse stroke could potentially be improved by timely intervention and highlight the importance of collaboration between cardiologists and neurologists to optimize AISCT outcomes.

Acute kidney injury (AKI) is a complication of percutaneous coronary intervention (PCI), known to increase rates of adverse medical events. We aimed to identify the optimal definition of AKI in predicting adverse cardiovascular outcomes and mortality post PCI. From a large registry of patients undergoing PCI between 2006-2018 (n = 25,690) at our medical center, consecutive patients were assessed for the presence of AKI according to four different definitions: a relative elevation of ≥25% or ≥50%; or an absolute elevation of ≥0.3 mg/dL or ≥0.5 mg/dL in serum creatinine at 48 hours post PCI. We assessed the calculated rates of AKI according to the different definitions. The discriminant capacity for 30-day and 1-year mortality and MACE (MACE: all-cause death, myocardial infarction, target-vessel revascularization and coronary artery bypass graft surgery) of each definition was calculated using ROC curves and AUCs. Data of 15,153 patients was available for the final analysis. Rates of AKI were 12.1%, 3.2%, 8.1% and 3.9% according to the four definitions, respectively. The discriminant capacity of adverse outcomes was highest among those defined as AKI according to the third definition - an absolute elevation of ≥0.3 mg/dL in serum creatinine with an AUC of 0.82 (95% CI 0.80-0.84) for 30-day mortality (P value = 0.036) and an AUC of 0.78 (CI 0.76-0.79) for 30-day MACE. In conclusion, an absolute elevation of ≥ 0.3 mg/dL in serum creatinine 48 hours post PCI predicts overall mortality and MACE most accurately.

Coronary artery disease (CAD) is very common in dialysis patients. One third have preexisting CAD and another one third have significant occult disease at the time of starting dialysis. Symptoms are often absent or are atypical, emphasizing the need for vigorous screening, specifically in patients awaiting transplant. The lesions tend to be heavily calcified, diffuse, and involve multiple vessels, consequently, percutaneous coronary interventions are more complicated to perform, and are less successful in achieving and maintaining short- and long-term patency. Dialysis patients have been excluded from the randomized controlled trials on which the current standards for managing CAD have been established. Due to differences in pathobiology and risks and benefits, it is uncertain that the results of these clinical trials extrapolate to patients with advanced chronic kidney disease (CKD). Here we review the data from observational studies and identify special considerations concerning the diagnosis and management of CAD in dialysis patients, including the use of noninvasive functional testing vs anatomical testing, the management of acute coronary syndromes and of stable coronary artery disease, the role for percutaneous revascularization vs coronary artery bypass grafting, and of platelet inhibitor therapy after coronary stenting. We review the preliminary results of the recently published ISCHEMIA-CKD trial, the only trial to date to involve large numbers of dialysis patients. This is the first of, hopefully, many trials in the pipeline that will examine therapies for CAD specifically in patients with advanced CKD, a growing population that is at particularly high risk for poor outcomes.

The choice between mechanical valves (MVs) and bioprosthetic valves (BVs) in patients undergoing aortic valve surgery is complex, requiring a balance between the inferior durability of BV and the indicated long-term anticoagulation therapy with MV. This is especially challenging in the middle age group (70 years), which has seen an increased use of BV over recent years.A meta-analysis of randomised controlled trials (RCTs), observational studies using propensity score matching (PSM) and inverse probability weighting (IPW) was conducted to examine the clinical outcomes of patients70 years of age undergoing aortic valve replacement. The primary outcome was overall long-term mortality. Secondary outcomes included bleeding events, reoperation, systemic thromboembolism, and cerebrovascular accident.Fifteen studies (1 RCT, 12 PSM studies, and 2 IPW studies; aggregated sample size 16,876 patients) were included. Median follow-up was 7.8 years. Mortality was higher with BVs vs MVs (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.00-1.49), as was reoperation (HR 3.05, 95% CI 2.22-4.19). Bleeding risk was lower with BVs (HR 0.58, 95% CI 0.48-0.69), and the risk of stroke was similar in both valve types (HR 0.96, 95% CI 0.83-1.11) CONCLUSIONS: This broadest meta-analysis comparing BV and MV suggests a survival benefit for MVs in patients70 years of age. This should lead to reassessment of current patterns used in the choice of valves for patients70 among the cardiothoracic surgery community.

Background Right heart catheterization (RHC) and echocardiography are both routinely used for pulmonary hypertension (PH) assessment in LT candidates, although this is not mandatory according to guidelines. We aim to describe the correlation between the pulmonary artery systolic pressure (PASP) measured by echocardiography to that measured by RHC in this population. Methods From a retrospective registry of 461 LT candidates, undergoing RHC between 2015–2019, 393 consecutive patients were assessed for the presence of pulmonary hypertension according to two methods – echocardiography and RHC. The primary outcome was the correlation between the estimated PASP measured by echocardiography to that measured by RHC. Secondary outcome was the accuracy of the echocardiographic assessment of PH. Results Patients were predominantly males (63.6%) with a mean age of 61.46±8.33y. The two most common etiologies for lung failure were interstitial lung disease or pulmonary fibrosis (52.2%) and chronic obstructive pulmonary disease (30.5%). Estimated PASP as measured by echocardiography was available in 89.31% of the patients, with a mean value of 49.5±20.02 mmHg. Mean PASP measured by RHC was 42.47±17.96 mmHg. The correlation between the two measurements was moderate (Pearson's correlation: r=0.609, p10 mmHg differences between the two values in 79.9% of the patients. Conclusions In the pre-surgical evaluation of LT candidates, echocardiographic estimation of PASP has moderate correlation with the PASP measured by RHC and relatively poor accuracy. Funding Acknowledgement Type of funding sources: None.

OBJECTIVES The immunogenicity of two-dose severe acute respiratory syndrome coronavirus 2 vaccine is lower among heart transplant (HTx) recipients, compared with the general population. Our aim was to assess the immunogenicity of a third-dose vaccine in HTx recipients. METHODS This is a prospective cohort study of HTx recipients who received a third dose of the BNT162b2 vaccine. Immunogenicity was assessed by serum levels of anti-spike immunoglobulin G (S-IgG), taken at baseline and 14–28 days after the third dose. Titres above 50 U/ml were interpreted positive. RESULTS We Included 42 HTx recipients at a median age of 65 years [interquartile range (IQR) 58–70]. At baseline, the median of 27 days (IQR 13–42) before the third dose and the median titre of the whole group was 18 U/ml (IQR 4–130). Only 14 patients (33%) were S-IgG seropositive. After the third dose, the proportion of seropositive patients increased significantly to 57% (P = 0.05) and the median titre increased significantly to 633 U/ml (IQR 7–6104, P < 0.0001). Younger age at HTx (OR per 1-year decrease 1.07, P = 0.05), low tacrolimus serum level (OR per 1-unit decrease 2.28, P = 0.02), mammalian target of rapamycin use (OR 13.3, P = 0.003), lack of oral steroids use (OR 4.17, P = 0.04) and lack of calcineurin inhibitor use (71% of responders vs 100% non-responders received calcineurin inhibitors, P = 0.01) were predictors of seropositive result after the third dose. However, no significant association was detected following adjustment for baseline S-IgG titre. CONCLUSIONS Third-dose booster of BNT162b2 vaccine significantly increased immunogenicity among HTx recipients who previously received a two-dose vaccine.

Introduction: We aimed to compare the outcomes of acute coronary syndrome (ACS) patients undergoing in-hospital percutaneous coronary intervention treated with prasugrel versus ticagrelor. Methods: Among 7,233 patients enrolled to the Acute Coronary Syndrome Israeli Survey (ACSIS) between 2010 and 2018, we identified 1,126 eligible patients treated with prasugrel and 817 with ticagrelor. Comparison between the groups was performed separately in ST-elevation myocardial infarction (STEMI) patients, propensity score matched (PSM) STEMI patients, and non-ST-elevation ACS (NSTE-ACS) patients. Results: In-hospital complication rates, including rates of stent thrombosis, were not significantly different between groups. In PSM STEMI patients, 30-day re-hospitalization rate (p < 0.05), 30-day MACE (the composite of death, MI, stroke, and urgent revascularization, p = 0.006), and 1-year mortality rates (p = 0.08) were higher in the ticagrelor group compared to the prasugrel group; in NSTE-ACS patients, outcomes were not associated with drug choice. In Cox regression analysis applied on the entire cohort, prasugrel was associated with lower 1-year mortality in STEMI patients but not in NSTE-ACS patients (p for interaction 0.03). Conclusions: Compared to ticagrelor, prasugrel was associated with superior clinical outcomes in STEMI patients, but not in NSTE-ACS patients.

Aims We aimed to compare the long-term outcomes of patients undergoing percutaneous coronary intervention (PCI) with biodegradable polymer drug-eluting stents (BP-DES) versus durable polymer drug-eluting stents (DP-DES). Methods and results Among 11 517 PCIs with second-generation DES performed in our institution between 2007 and 2019, we identified 8042 procedures performed using DP-DES and 3475 using BP-DES. The primary outcome was target lesion failure, the composite target lesion revascularization (TLR), target vessel myocardial infarction and death. Propensity score matching was used to create a well-balanced cohort. Mean follow-up was 4.8 years. Of the 3413 matched pairs, 21% were females, and the mean age was 66 years. At 1 year, the primary outcome occurred in 8.3% patients versus 7.1% (P = 0.07), and TLR rate was 3% versus 2% (P = 0.006) in patients with DP-DES and BP-DES respectively. Within 5 years, the primary outcome occurred in 23.1% versus 23.4% (P = 0.44), and the rate of TLR was 7.2% versus 6.5% (P = 0.07) in patients with DP-DES and BP-DES, respectively. Conclusion Similar rates of the composite outcome were observed throughout the entire follow-up. target vessel revascularization rates were lower in the DP-DES group at 1 year but equalized within 5 years.

The aim of this study was to evaluate the outcome of transcatheter mitral valve repair (TMVr) in patients with cardiogenic shock and significant mitral regurgitation (MR).Patients in cardiogenic shock with severe MR have a poor prognosis in the setting of conventional medical therapy. Because of its favorable safety profile, TMVr is being increasingly used as an acute therapy in this population, though its efficacy remains unknown.A multicenter, collaborative, patient-level analysis was conducted. Patients with cardiogenic shock and moderate to severe (3+) or severe (4+) MR who were not surgical candidates were treated with TMVr. The primary outcome was in-hospital mortality. Secondary outcomes included 90-day mortality, heart failure (HF) hospitalization, and the combined event rate of 90-day mortality and HF hospitalization following dichotomization by TMVr device success.Between January 2011 and February 2019, 141 patients across 14 institutions met the inclusion criteria. In-hospital mortality occurred in 22 patients (15.6%), at 90 days in 38 patients (29.5%), and at one year in 55 patients (42.6%). Median length of hospital stay following TMVr was 10 days (interquartile range: 6 to 20 days). HF hospitalization occurred in 26 patients (18.4%) at a median of 73 days (interquartile range: 26 to 546 days). When stratified by TMVr procedural results, successful TMVr reduced rates of in-hospital mortality (hazard ratio [HR]: 0.36; 95% confidence interval [CI]: 0.13 to 0.98; p = 0.04), 90-day mortality (HR: 0.36; 95% CI: 0.16 to 0.78; p = 0.01), and the composite of 90-day mortality and HF hospitalization (HR: 0.41; 95% CI: 0.19 to 0.90; p = 0.03).TMVr may improve short- and intermediate-term mortality in high-risk patients with cardiogenic shock and moderate to severe MR. Randomized studies are needed to definitively establish MR as a therapeutic target in patients with cardiogenic shock.

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.

Risk-benefit assessment for transcatheter aortic valve implantation (TAVI) is still evolving. A sizeable group of patients do not fully benefit from intervention despite a technically successful procedure. All patients who underwent TAVI with device success and with no Valve Academic Research Consortium (VARC)-2 defined complications were included. Various demographic data, clinical details, and echocardiographic findings were examined. The outcome was defined as 1-year composite of mortality, stroke, lack of functional-class improvement (by New York Heart Association class), and readmissions (≥1 month after the procedure). Logistic regression was used to fit the prediction model. We used a 10-fold cross-validation to validate our results. Of 543 patients, 435 met the inclusion criteria. The mean age was 82 (±6.5) years, 43% were men, and the mean Society of Thoracic Surgeons score was 6.6 (±4.7). At 1 year, 66 of 435 patients (15%) experienced the study end point. The final logistic regression model included diabetes, baseline New York Heart Association functional class, diastolic dysfunction, need for diuretics, mean gradient, hemoglobin level, and creatinine level. The area under the curve was 0.73 and was reduced to 0.71 after validation, with a 97% specificity using a single cutoff. Dividing to low-, medium-, and high-risk groups for futility produced a corresponding prevalence of 6%, 19%, and 59% futility. A web application for the prediction model was developed and provided. In conclusion, this prediction score may provide an important insight and may facilitate identification of patients who, despite a technically successful and uncomplicated procedure, have risk that may outweigh the benefit of a contemplated TAVI.

BackgroundDecisions on dual antiplatelet therapy (DAPT) duration should balance the opposing risks of ischaemia and bleeding. Our aim was to develop a risk score to identify stable coronary artery disease (SCAD) patients undergoing PCI who would benefit or suffer from extending DAPT beyond 6 months.MethodsRetrospective analysis of a cohort of patients who completed 6 months of DAPT following PCI. Predictors of ischaemic and bleeding events for the 6-12 month period post-PCI were identified and a risk score was developed to estimate the likelihood of benefiting from extending DAPT beyond 6 months. Incidence of mortality, ischaemic and bleeding events for patients treated with DAPT for 6 vs. 6-12 months, was compared, stratified by strata of the risk score.ResultsThe study included 2,699 patients. Over 6 months' follow up, there were 78 (2.9%) ischaemic and 43 (1.6%) bleeding events. Four variables (heart failure, left ventricular ejection fraction ≤30%, left main or three vessel CAD, status post (s/p) PCI and s/p stroke) predicted ischemic events, two variables (age>75, haemoglobin ConclusionIn a population of SCAD patients who completed 6 months of DAPT, a risk score for subsequent ischaemic and bleeding events identified patients likely to benefit from continuing or stopping DAPT.

OBJECTIVES To estimate the prevalence, identify predictors, and assess the prognostic implications of left ventricular ejection fraction (LVEF) changes after an elective percutaneous coronary intervention (PCI). METHODS We included all consecutive patients who underwent elective PCI in our institution and were evaluated with echocardiography before and within 1 year of the procedure. Patients were grouped in terms of baseline LVEF. Hazard ratios (HRs) for all-cause mortality and acute myocardial infarction were calculated for baseline LVEF groups and in terms of LVEF normalization or decline. RESULTS A total of 974 patients were included. Patients with moderately impaired (HR 1.41, P=0.01) and poor LVEF (HR 2.44, P

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.

Transfemoral Transcatheter Aortic Valve Replacement (TAVR) carries a risk of Vascular Complications (VCs) at the access site. The currently used measures for assessing the risk for VCs are not accurate enough, and sometimes fail to predict them. We therefore aimed to examine whether Iliofemoral artery lumen volume (IFV) assessment with 3-dimensional computed tomography (CT) predicts VCs after transfemoral TAVR.We identified 45/560 trans-femoral TAVR patients with VC, then performed nearest neighbor 1:1 matching for patients with no VC, matching for age, sex, TAVR year, valve size and type, closure-device, sheath size and peripheral vascular disease. IFV, minimal diameter, tortuosity, and calcification were measured, and their diagnostic performance assessed.The final analysis included 45 patients with and 45 patients without VCs. The two groups were well balanced. For all patients, median IFV was 8.65 ml (IQR 6.5-11.95). IFV was lower in patients with VC compared to patients without VC: 7.10 ml (IQR 5.4-9.0) vs. 10.10 ml (IQR 8.3-13.3), p 0.001. VC risk had marginal association with iliofemoral artery minimal diameter (p = 0.06) and no association with tortuosity or calcification. Compared with other measurements, IFV had the most favorable receiver operating curve for the prediction of VC, with an area under the curve (AUC) of 0.78.IFV measurement using 3-dimensional CT is significantly associated with VCs in transfemoral TAVR patients and might be superior to currently accepted parameters. IFV should be further studied among extended cohorts of TAVR treated patients as a novel tool for VC risk assessment prior to transfemoral TAVR.

Circulating endothelial progenitor cells have an important role in the process of vascular repair. Impaired recruitment and function of endothelial progenitor cells is related to the pathophysiology of congestive heart failure. Endothelial progenitor cells have been shown to express the mineralocorticoid receptor.To investigate the effect of mineralocorticoid receptor antagonists on endothelial progenitor cells in patients with heart failure.Twenty-four patients with compensated heart failure, who were not under mineralocorticoid receptor antagonist therapy, were recruited. Either eplerenone (n=8) or spironolactone (n=16) therapy was initiated. Circulating endothelial progenitor cell level, identified as the proportion of mononuclear cells expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34, was evaluated by flow cytometry at baseline and after 8 weeks. Following 7 days of culture, colonies were counted by microscopy and MTT assay was performed on randomly selected patients (n=12) to estimate viability.Both median CD34+/VEGFR2+ and median CD133+/VEGFR2+ increased significantly (P = 0.04 and 0.02, respectively). However, the number of colonies and viability of the cells after therapy (as assessed by the MTT assay) was not significantly different compared with the baseline.These preliminary results suggest that mineralocorticoid receptor blockade may enhance endothelial progenitor cells recruitment in patients with compensated heart failure.

Family history of premature cardiovascular disease (FHpCVD) is a well-established risk factor for development of coronary artery disease. However, little is known about the impact of FHpCVD on the outcome of patients presenting with acute coronary syndrome (ACS). We therefore aimed to evaluate the outcomes of ACS patients grouped by the presence and/or absence of FHpCVD. All patients ≤65 at admission who had an ACS event and were enrolled in the national ACS Israel Survey registry from 2000 to 2013 were included. Patients were grouped by the presence or absence of self-reported FHpCVD. Nearest neighbor propensity score matching was applied to create an evenly matched cohort of patients. Outcomes included 30-day MACE (defined as the composite of death, unstable angina pectoris, myocardial infarction, stroke, stent thrombosis, and urgent revascularization) and its individual components. Of 7,173 ACS patients, 33.9% reported FHpCVD. These patients were younger, with lower prevalence of diabetes, previous cerebrovascular and kidney diseases, but had higher prevalence of smoking and hyperlipidemia (p0.001 for each). The propensity score-matching cohort included 1,793 pairs of evenly matched patients. The rate of 30-day MACE did not differ in the groups, as well as 1-year mortality (2.4% vs 2.2%, with vs without FHpCVD, respectively). During long-term follow-up (median 7.6 years), mortality rate was lower in the FHpCVD group (hazard ratio 0.82, 95% confidence intervals 0.69 to 0.99). In conclusion, we observed no differences in short- and intermediate-term outcomes based on the presence and/or absence of FHpCVD. However, patients with FHpCVD had better long-term survival.

Background/Aim Hyperhomocysteinemia and hyperuricemia are both considered risk factors for coronary artery disease. However, the relationship between the 2 has not yet been thoroughly investigated. This study aimed to evaluate this relationship more closely. Material and Methods This study is a retrospective cross-sectional analysis of data from a screening center in Israel assessing 16,477 subjects, within an age range of 20 to 80 years. Results The mean age of the study sample was 46 years, and 68% were males. Hyperuricemia was found in 24.9% and 14.6% of subjects with elevated and normal homocysteine serum levels, respectively ( P < 0.001). A positive association was found between homocysteine serum levels and uric acid serum levels. Compared with subjects with normal homocysteine serum levels, those with hyperhomocysteinemia had an odds ratio (OR) for hyperuricemia of 1.7 (95% confidence interval [CI], 1.5–1.9) and 1.6 (95% CI, 1.1–2.5) for males and females, respectively. After multivariate adjustment for age, hypertension, body mass index, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and thiazide use, the association remained significant in males (OR, 1.5; 95% CI, 1.3–1.7; P < 0.001) but not in females (OR, 0.9; 95% CI, 0.6–1.6; P = 0.82). Conclusions This large cohort showed a significant association between hyperhomocysteinemia and hyperuricemia. Sex differences were observed. This study suggests that accelerated atherosclerosis may be a consequence of the combined effect of these 2 factors.

Risk assessment for transcatheter aortic valve implantation (TAVI) patients remains challenging, especially in elderly and high-risk candidates. Although several risk factors contribute to increased morbidity and mortality after TAVI, simple risk scores for routine use are lacking. Applying the CHA

Advanced chronic kidney disease (CKD) is an independent predictor of mortality in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to identify predictors of 1-year mortality in patients after TAVI stratified by the presence or absence of advanced CKD (defined as estimated glomerular filtration rate

Both cigarette smoking and chronic kidney disease (CKD) are linked to cardiovascular morbidity and development of atherosclerosis. However, the relationship between cigarette smoking and renal function is not clearly understood.To investigate the relationship between cigarette smoking and renal function, and determine whether the intensity of cigarette smoking influences renal function.We conducted a retrospective analysis of subjects attending the screening center at the Rabin Medical Center. Subjects were classified as smokers, non-smokers and past smokers. Renal function was evaluated by means of the CKD-EPI equation for estimating glomerular filtration rate (eGFR). Multivariate and gender-based analyses were performed.The study population comprised 24,081 participants, of whom 3958 (17%) were classified current smokers, and 20,123 non-smokers of whom 4523 were classified as past smokers. Current smokers presented a higher eGFR compared to the non-smoking group (100.8 vs. 98.7, P0.001) as well as higher rates of proteinuria (15.3% vs. 9.3%, P0.001). The difference in eGFR between smokers and non-smokers was more significant in males than in females. Past smokers had the lowest eGFR of all groups, this difference remained significant after age adjustments (P = 0.005).Cigarette smoking is associated with higher eGFR compared to non-smoking. This difference was more pronounced in males than females, implying a gender-based difference. The higher prevalence of proteinuria in smokers suggests a mechanism of hyperfiltration, which might result in future progressive renal damage.

The MGuard™ stent (InspireMD, Tel Aviv, Israel) is a bare metal mesh-covered stent, developed to prevent no-reflow phenomenon during percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) and acute myocardial infarction (MI), both associated with significant atherothrombotic lesions.To report on local experience with patients treated with the MGuard stent until follow-up at 1 year.We followed 163 consecutive patients who underwent MGuard stent deployment during the period 2009 to 2014 in a large tertiary cardiac center in central Israel.The MGuard stent was used in 67% of patients who underwent SVG-PCI while 33% were treated for native coronary artery disease, the majority during ST-elevation MI (STEMI). The mean age was 67 years and 83% were males. The clinical presentation was STEMI in 30% and non-STEMI/unstable angina in 60% of patients. Of the total number of patients, 47% had diabetes and 29% had chronic kidney disease. All patients had follow-up at 1 year. Mortality in the native group was 1.9% vs. 10% in the vein graft cohort. ST was 2% in both groups. The major adverse cardiac event (MACE) rates were 11% in the native artery and 29% in the vein graft group, mainly due to respective target lesion revascularization/target vessel revascularization rates of 6% and 7% in the native vessel group and 11% and 15% in the SVG group.In suitable patients undergoing SVG-PCI or native lesion intervention during acute MI, the MGuard stent is a viable treatment strategy. Its potential merits and limitations warrant further evaluation.

The Evolut-R (Medtronic, Inc) is a transcatheter aortic valve implantation (TAVI) system that was built on the well-established foundation of Medtronic's CoreValve device platform. Although already in extensive clinical utilization, it is unknown if the Evolut-R improves TAVI outcomes. Herein, we compared TAVI outcomes of the Evolut-R and CoreValve devices.A propensity score 1:1 matching was conducted on 358 Evolut-R patients (n = 75) and CoreValve patients (n = 283). Thirty-day outcomes were compared using Valve Academic Research Consortium (VARC)-2 criteria. A combined 30-day endpoint including all-cause death, stroke, major vascular complication, major bleeding, implantation failure, paravalvular leak (PVL) ≥ moderate, and new pacemaker implantation was also tested.The final study group included 146 patients (73 Evolut-R; 73 CoreValve). Post matching, baseline characteristics were similar between the two groups. Mean patient age was 82 ± 6 years, mean STS score was 5.2 ± 3.8, 72% were female, and 17% were deemed frail. Implantation success reached 99% with Evolut-R and 94% with CoreValve (P=.10). Both groups had low periprocedural stroke/myocardial infarction/mortality rates and there was also no difference in 30-day vascular complications (P=.18), bleeding (P=.37), PVL (P=.24), and new pacemaker (P=.14). The combined outcome rate was 24% with Evolut-R and 37% with CoreValve (P=.10).This study indicates that the efficacy and safety of the self-expandable second-generation Evolut-R transcatheter valve is at least comparable with the first-generation CoreValve. The observed improved performance in correct positioning of a single valve and the numerically lower chance to suffer a combined TAVI endpoint needs further investigation.

Transcatheter aortic valve implantation (TAVI) is an established treatment for severe aortic stenosis in patients at high or prohibitive surgical risk. Nevertheless, long-term clinical and echocardiographic data are still lacking. We carried out an analysis of 560 consecutive patients who underwent TAVI at our institution from 2008 to 2016 to evaluate temporal changes in TAVI characteristics, predictors of 1-year and long-term outcomes, and to compare the performance of the early- and new-generation valve systems. With time, we have adopted lower risk threshold for patient selection and have been using conscious sedation and transfemoral access preferentially (p0.001 for all). The incidence of greater than mild PVL decreased from 16% to 7.6%, p = 0.029. Within 5 years, 47% of the patients died, the majority (78%) due to noncardiac causes. Independent predictors of 1-year death included periprocedural aspects (i.e., vascular complications, stroke, and PVL), whereas death occurring later than 1 year was solely related to baseline co-morbidities. Transvalvular gradients and residual regurgitation remained nonclinically significant for up to 5 years of follow-up. New-generation valves were associated with less PVL compared with propensity score-matched early-generation valves (p0.001). In conclusion, TAVI utilization at our institution has progressed to include lower risk patients with transfemoral access becoming applicable in the great majority. Poor long-term survival is attributable to population factors rather than to procedural factors. Intermediate- and long-term hemodynamics are excellent. PVL has diminished significantly with the new-generation valves. Efforts to improve long- and short-term outcomes remain a therapeutic challenge.

Background Endothelial progenitor cells (EPCs) are a population of bone marrow-derived cells, which have an important role in the process of endothelialization and vascular repair following injury. Impairment of EPCs, which occurs in patients with diabetes, was shown to be related to endothelial dysfunction, coronary artery disease (CAD) and adverse clinical outcomes. Recent evidence has shown that calcitriol, the active hormone of vitamin D, has a favorable impact on the endothelium and cardiovascular system. There is limited data on the effect of vitamin D on EPCs function. Aim To examine the in vitro effects of Calcitriol on EPCs from healthy subjects and patients with diabetes. Methods Fifty-one patients with type 2 diabetes (60±11 years, 40% women, HbA1C: 9.1±0.8%) and 23 healthy volunteers were recruited. EPCs were isolated and cultured with and without calcitriol. The capacity of the cells to form colony-forming units (CFUs), their viability (measured by MTT assay), KLF-10 levels and angiogenic markers were evaluated after 1 week of culture. Results In diabetic patients, EPC CFUs and cell viability were higher in EPCs exposed to calcitriol vs. EPCs not exposed to calcitriol [EPC CFUs: 1.25 (IQR 1.0–2.0) vs. 0.5 (IQR 0.5–1.9), p < 0.001; MTT:0.62 (IQR 0.44–0.93) vs. 0.52 (IQR 0.31–0.62), p = 0.001]. KLF-10 levels tended to be higher in EPCs exposed to vitamin D, with no differences in angiopoietic markers. In healthy subjects, calcitriol supplementation also resulted in higher cell viability [MTT: 0.23 (IQR 0.11–0.46) vs. 0.19 (0.09–0.39), p = 0.04], but without differences in CFU count or angiopoietic markers. Conclusion In patients with diabetes mellitus, in vitro vitamin D supplementation improved EPCs capacity to form colonies and viability. Further studies regarding the mechanisms by which vitamin D exerts its effect are required.

C reactive protein (CRP) is an acute phase reactant that primarily produced by hepatocytes yet may be locally expressed in renal tubular cells. We assessed the association of CRP and the risk for chronic kidney disease (CKD) development. Historical prospective cohort study was conducted on subjects attending a screening center in Israel since the year 2000. Subjects with an estimated GFR (eGFR) above 60 ml/min/1.73 m2 at baseline were included, and high sensitive (hs) CRP levels as well as eGFR were recorded for each visit. Follow up continued for at least 5 years for each subject until 2013. Risk for CKD at end of follow up was assessed in relation to mean hs-CRP levels of each subject. The confounding effects of other predictors of CKD were examined. A logistic regression model treating CRP as a continuous variable was further applied. Out of 4,345 patients, 42 (1 %) developed CKD in a mean follow up of 7.6 ± 2 years. Elevated levels of CRP were associated with greater risk for CKD (crude OR 4.17, 95 % CI 1.46–11.89). The OR for the association of CRP with CKD when controlling for age and gender was 5.2 (95 % CI 1.7–16.2). When controlling for established renal risk factors, elevated CRP levels remained significantly associated with greater risk for CKD (OR 5.42, 95 % CI 1.76–16.68). When applying logistic regression models treating CRP as a continuous variable, for patients with diabetes mellitus (DM), hypertension (HTN) or eGFR between 60–90 ml\min\1.73 m2, the predictive role of CRP for CKD was highly significant. Elevated CRP level is an independent risk factor for CKD development. In patients with DM, HTN or baseline eGFR between 60–90 ml\min\1.73 m2 its predictive role is enhanced.

BACKGROUND Limited contemporary data exist regarding the incidence, predictors, and outcomes of failure of primary percutaneous coronary intervention (PCI) in the treatment of ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS In this registry-based retrospective cohort study, all consecutive unselected patients (n=1725) who were hospitalized for STEMI and underwent primary PCI from January 2001 to December 2010 were included. PCI failure was defined as a final diameter stenosis greater than 30% or postdilatation Thrombolysis in Myocardial Infarction (TIMI) flow grade of 2 or less. We examined the predictors and survival among patients who failed primary PCI. RESULTS The overall PCI failure rate was 5.4% (94 of 1725 procedures). After adjusting for prespecified baseline characteristics, independent predictors of PCI failure included age greater than 65 years (P=0.02), procedure date between 2001 and 2005 (P=0.05), night-time PCI (P=0.008), calcific lesion (P=0.008), and lower preprocedural TIMI flow grade (P=0.006). Failed PCI was associated with a 1-year mortality rate of 22% as compared with 4.2% in the successful PCI group (P

This study was conducted to examine the relationship between the degree of asymptomatic hyperuricemia and the development of gout, in men and women. The database of a screening center was searched for all subjects with asymptomatic hyperuricemia (>7.0 mg/dl men, >5.6 mg/dl women) during 2000–2012. We included men and women without previous diagnosis of gout, and a follow-up of at least 5 years. The risk of gout was analyzed in relation to the degree of hyperuricemia at the first visit. Of the 5,234 subjects who matched the inclusion criteria, 4,241 were normouricemic at their first visit and 993 were hyperuricemic. The mean follow up period was 7.5 years. Gout was diagnosed at the last visit in 34 subjects; four in the normouricemia group and 30 in the hyperuricemia group (0.1 % vs. 3.0 %, p

Myonecrosis following PCI is a frequent impediment that may impact cardiac prognosis. The frequency of periprocedural myocardial infarction (PMI) in CTO-PCI is dependent on MI definition (biomarker and threshold), lesions characteristics, and PCI course. This study identified predictors of PMI during CTO-PCI and it showed that PMI and peak CK-MB level were associated with worse clinical outcomes.

The relationship between homocysteine levels and glaucoma has been questioned in previous studies without conclusive results. In the current study, we assessed the relationship between homocysteine levels and intraocular pressure which is one of the main factors in the development of glaucoma in men and women. A retrospective cross-sectional analysis of a database from a screening center in Israel which assessed 11,850 subjects, within an age range 20 to 80 years. The relationship between homocysteine and intraocular pressure has been investigated by comparing intraocular pressure in subjects with elevated and normal homocysteine and by comparing homocysteine levels in subjects with elevated and normal intraocular pressure. In addition, we compared the levels of homocysteine in subjects with and without a confirmed diagnosis of glaucoma. The mean IOP (±SD) in subjects with normal homocysteine levels(≤15 μmol/L) was 13.2 ± 2.3 mm Hg and 13.4 ± 2.4 mm Hg in those with high homocysteine levels (>15 μmol/L) (P

Background Transcatheter aortic valve implantation (TAVI) is recommended for patients with severe symptomatic aortic stenosis (AS) who are at prohibitive/high risk for surgical aortic valve replacement (SAVR). Patients with severe AS may experience acute decompensated heart failure (HF) that is resistant to medical therapy. We report our TAVI experience in treating patients with unstable AS who require urgent intervention for their aortic valve disease. Methods Patients were restrictively included in the urgent TAVI registry if they were admitted with acute refractory and persistent HF despite medical therapy and had TAVI performed during the same hospital stay. All others were included in the elective TAVI group. Results Between November 2008 and April 2015, 410 consecutive patients underwent TAVI at our centre—27 (6.6%) urgently. Patients operated on urgently were more likely to be frail and carry higher SAVR mortality risk based on The Society of Thoracic Surgeons Predicted Risk of Mortality/logistic EuroSCORE (LES) measures. Pulmonary edema was the most common clinical presentation. Preprocedural assessment used fewer imaging modalities, yet implantation success remained high and reached 96.3% using an additional valve (valve-within-valve) required in 3 patients, with no difference in periprocedural complications according to the Valve Academic Research Consortium-2 definitions. Although 30-day functional capacity was reduced, patients had similar 30-day mortality and major adverse cardiovascular event rates compared with patients who underwent elective TAVI. Conclusions Short-term outcome after urgent TAVI appears to be reasonable. For patients with severe AS who experience acute decompensated HF that is recalcitrant to optimal medical therapy and who are at high risk with SAVR, urgent TAVI may be a viable treatment strategy. Larger prospective studies and data on long-term outcomes are needed.

To investigate the in-hospital and long-term outcomes of patients at extreme age with severe symptomatic aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI).A total of 276 consecutive patients with a mean age of 82.2 ± 5.0 years with severe symptomatic AS underwent TAVI at our institute. We evaluated periprocedural, in-hospital, and long-term outcomes in all patients aged ≥87 years (the highest 20th percentile of age distribution) and compared them with the less elderly patients.The extremely aged group included 58 patients (21%) ≥87 years (mean age, 89.0 ± 1.9 years; 67.2% women). Baseline EuroSCOREs and STS scores were 19.6 ± 11.2% and 9.4 ± 5.0%, respectively. Nineteen patients (34.5%) were considered frail. Following TAVI, all patients regained New York Heart Association class 1-2 functional capacity. The main periprocedural and in-hospital complications were minor vascular complications, bleeding requiring blood transfusions, and the need for permanent pacemaker. None of the patients suffered from clinical stroke. In comparison to the less elderly patients, there were no significant differences in the rates of periprocedural, in-hospital complications or long-term survival (log rank, 0.87).Meticulously selected patients at extreme age benefit from TAVI with a reasonable overall risk, which does not impact the overall survival or functional status.

Background Timing of central venous catheter (CVC) insertion among patients with acute leukemia is debatable. Early insertion increases convenience, but might increase infection rates. Methods We assessed retrospectively the rate of central line-associated bloodstream infections (CLABSI) according to CVC time of insertion in patients with acute leukemia admitted for induction or salvage therapy. The study was conducted in the Hematology Department of a Tertiary hospital in Israel between 2007 and 2011. Early CVC placement was defined as CVC inserted during the first week of induction therapy. CLABSI rate was documented between the seventh day of induction therapy to 30 days after its completion. Results A total of 127 patients were included. Acute myeloid leukemia was the most common diagnosis (103 patients, 80.5%). Late CVC placement was associated with CLABSI after adjustment to the Charlson comorbidity index (OR 3.4, 95% CI 1.1–10.45), p = 0.03. Conclusion Delaying CVC placement in adult patients with acute leukemia may be associated with higher rate of CLABSI in the early period after induction therapy.

To estimate the effect of elevated serum homocysteine level on renal function decline and on the incidence of chronic kidney disease (CKD) in the general population.A historical prospective study on 3602 subjects attending a screening center in Israel between the years 2000 and 2012. Only subjects with normal estimated glomerular filtration rate (eGFR) and without proteinuria were included. Subjects were divided to two groups according to mean total serum homocysteine level (≤ 15,15μmol/l). Linear mixed effect model was used to estimate the annual eGRF decline in respect to homocysteine group. Cox proportional hazards models were used to estimate hazard ratios for CKD in the normal compared to the elevated homocysteine group.Annual eGFR decline was 25% higher in subjects with elevated versus normal mean homocysteine level (0.90 ± 0.16 ml/min/1.37 m(2) vs. 0.72 ± 0.14 ml/min/1.37 m(2), p0.001). In a median follow up of 7.75 years, 38 subjects developed CKD (1.05%). Elevated mean homocysteine level was highly associated with developing CKD (HR 4.85, 95% CI 2.48-9.49, p0.001). In a multivariate analysis which adjusted for age, baseline kidney function, HDL cholesterol, BMI, vitamin B12 and folic acid levels, these relationships remained substantially unchanged.Elevated mean serum homocysteine level is associated with an accelerated decline in renal function in both men and women, and is an independent risk factor for the development of CKD in the general population. Further prospective randomized clinical trials are needed to clarify whether the reduction in serum homocysteine concentrations will result in an improved renal prognosis.

Objectives: This study sought to explore the frequency and prognostic implications of infectious and noninfectious fever following transcatheter aortic valve implantation (TAVI). Methods: We performed a retrospective cohort study including 194 consecutive patients who underwent TAVI at our institution. We identified and characterized all patients who developed fever within the first 72 h following the procedure. We determined the etiology of the fevers (infectious vs. noninfectious) and assessed their impact on in-hospital complications and 1-year mortality. Results: Following TAVI, 65 (33.5%) patients had fever (mean age 83.7 ± 3.8 years, 70.2% female). An infectious etiology was evident in only 17 of the 65 patients (26.1%) with fever, mainly due to pneumonia (52.9%) and a urinary tract infection (41.2%). No significant difference was observed in baseline characteristics, the mean fever temperature/duration, or signs of inflammatory response between infectious and noninfectious fevers. The mean hospital duration was longer (7 ± 4.8 days vs. 4.7 ± 2.4 days, p = 0.01) among patients with an infectious fever; however, fever had no impact on the 1-year mortality rate (5.9 and 4.5%, respectively, p = 0.71). Conclusions: Our study demonstrates that, although fever was a common phenomenon after TAVI, it represented an infectious complication only in a minority of cases. Nevertheless, fever, infectious or not, had no impact on the 1-year mortality rate following TAVI.