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Contemporary data on the independent association of severe tricuspid regurgitation (TR) with excess mortality are needed. The aims of this study were to describe contemporary outcomes of patients with severe TR and to identify outcome modifiers.Consecutive echocardiographic reports linked to clinical data from the largest medical center in Israel (2007-2019) were reviewed. The primary outcome was all-cause mortality. Cox regression and propensity score matching models were applied.The final cohort included 97,096 patients. Mild, moderate, and severe TR was documented in 27,147 (28%), 2,844 (3%) and 1,805 (2%) patients, respectively. During a median follow-up period of 5 years (interquartile range, 2-8 years), 22,170 patients (23%) died. Kaplan-Meier survival analysis demonstrated an increased risk for death with an increasing degree of TR (log-rank P .001). Propensity score matching of 1,265 patients with severe TR and matched control subjects showed that compared with those with nonsevere TR, patients with severe TR were 17% more likely to die (95% CI, 1.05-1.29; P = .003). The association of severe TR with survival was dependent on estimated right ventricular (RV) pressure, with a more pronounced effect among patients with estimated systolic pressure ≤ 40 mm Hg (hazard ratio, 2.12 vs 1.04; P for interaction.001). A landmark subanalysis of 17,967 patients demonstrated that RV function deterioration on follow-up echocardiography modified the association of severe TR with survival. It was more significant among patients with preserved and stable RV function (P for interaction = .035).The outcome of severe TR is modified by RV pressure and function. Once RV function deteriorates, differences in the outcomes of patients with and without severe TR are less pronounced.

OBJECTIVES Type 2 diabetes mellitus (DM) is a frequent comorbidity among patients suffering from advanced heart failure necessitating a left ventricular assist device (LVAD) implant. The goal of this study was to evaluate the impact of type 2 DM on early and long-term outcomes of patients following an LVAD implant. METHODS We performed an observational cohort study in a large tertiary care centre in Israel. All data of patients who underwent a continuous flow LVAD implant between 2006 and 2020 were extracted from our departmental database. Patients were divided into 2 groups: group I (patients without diabetes) and group II (patients with diabetes). We compared short-term (30-day and 3-month) mortality, intermediate-term (1- and 3-year) mortality and long-term (5 year) mortality between the 2 groups. RESULTS The study population included 154 patients. Group I (patients without diabetes) comprised 88 patients and group II (patients with diabetes) comprised 66 patients. The mean follow-up duration was 38.2 ± 30.3 months. Short- and intermediate-term mortality (30 days, 1 year and 3 years) was higher in the group with DM compared with the group without DM but did not reach any statistically significant difference: 16.1% vs 9.8% (P = 0.312), 24.2% vs 17.3% (P = 0.399) and 30.6% vs 21.9% (P = 0.127) respectively. Long-term 5-year mortality was significantly higher in the group with DM compared to the group without: 38.7% vs 24.4% (P = 0.038). Furthermore, predictors of long-term mortality included diabetes (hazard ratio 2.09, confidence interval 1.34–2.84, P = 0.004), as demonstrated by regression analysis. CONCLUSIONS Patients with diabetes and those without diabetes have similar 30-day and short- and intermediate-term mortality rates. The mortality risk of diabetic patients begins to increase 3 years after an LVAD implant. Diabetes is an independent predictor of long-term, 5-year mortality after an LVAD implant. Clinical trial registration Ethical Committee of Sheba Medical Centre, Israel, on 2 December 2014, Protocol 4257.

The Yarmouk River gorge extends along the Israel–Jordan–Syria border junction. It marks the southern bound of the Irbid–Azraq rift and Harrat Ash Shaam volcanic field at their intersection with the younger Dead Sea Transform plate boundary. During the last ∼13 Ma, the gorge has repeatedly accumulated basaltic units, chronologically named the Lower, Cover, Yarmouk and Raqqad Basalt formations. We examined their origin and distribution through aerial photos, and geological and geophysical evidence. Our results define a southern Golan magmatic province, which includes exposed Miocene (∼13 Ma) basalts, gabbro–diabase intrusions below the gorge and the adjacent Dead Sea Transform valley, and numerous Pliocene–Pleistocene volcanic sources along the gorge. Cover Basalt (∼5.0–4.3 Ma) eruptions formed two adjacent 0–100 m thick plateaus on the transform shoulder before flowing downslope to fill the topographically lower Dead Sea Transform valley with ∼700 m thick basalts. Later incision of the Yarmouk River and displacement along its associated fault divided the plateaus and formed the gorge. The younger Yarmouk (0.8–0.6 Ma) and Raqqad (0.2–0.1 Ma) basalts erupted in the upper part of the gorge from volcanos reported here, and flowed downstream toward the Dead Sea Transform valley. Consequently, eruptions from six phreatic volcanic vents altered the Yarmouk River morphology from sinuous to meandering. Our results associate the ∼13 Ma long southern Golan volcanism with the proposed SW-trending extensional Yarmouk Fault, located east of the Dead Sea Transform. Hence, the Yarmouk volcanism is associated with the ongoing Harrat Ash Shaam activity, which is not directly linked to the displacement along the Dead Sea Transform.

There is a growing interest in transcutaneous aortic valve implantation (TAVI) therapy among patients with bicuspid severe aortic stenosis (BAV). Conduction disturbances remain a frequent complication of TAVI, and new-onset permanent LBBB (NOP-LBBB) post-TAVI may be a marker of worse outcomes. We aimed to evaluate the rate of NOP-LBBB following TAVI among patients with BAV as compared to tricuspid severe aortic stenosis (TAV). Patients enrolled in the multicenter (5 centers) Bicuspid AS TAVI Registry were reviewed and compared with patients with TAV. Patients with previous aortic valve replacement, other valve morphologies and those with preprocedural LBBB or pacemaker were excluded. NOP-LBBB was defined as LBBB first detected and persisting 30-days following TAVI. A total of 387 patients (66 with BAV, 321 with TAV), age 80.3 ± 7.3, 47% females were analyzed. The device success rates were 95% in both groups without any conversions to surgery. The rate of NOP-LBBB was significantly higher among patients with BAV versus TAV (29.2% vs 16.9%, p = 0.02). However, the rate of post procedural pacemaker implantation was similar (14.8% vs 12.5%; respectively, p = 0.62). In BAV and TAV groups, 1-year mortality (6.1% vs 7.2%; respectively, p = 0.75) and stroke rates (6.1% vs 3.5%; respectively, p = 0.30) were not significantly different. Multivariate analysis identified BAV as an independent predictor of NOP-LBBB (AdjOR = 2.7, 95%CI 1.3 to 5.4). Furthermore, BAV subtypes with raphe (type 1) were identified as independent predictors of NOP-LBBB (AdjOR = 3.2, 95%CI: 1.5 to 6.7). In conclusion, patients with BAV undergoing TAVI have greater risk for developing NOP-LBBB compared with patients with TAV and the presence of raphe was associated with increased risk of NOP-LBBB. The prognostic significance for this finding warrants further evaluation in future studies.

The treatment of choice for severe rheumatic mitral stenosis is balloon mitral valvuloplasty (BMV). Numerous predictors of immediate and long-term procedural success have been described. The aims of this study were to describe our experience with BMV over the last decade and to evaluate predictors of long-term event-free survival.Medical records were retrospectively analyzed of patients who underwent BMV between 2009 and 2021. The primary outcome was a composite endpoint of all-cause mortality, mitral valve replacement (MVR), and repeat BMV. Long-term event-free survival was estimated using the Kaplan-Meier curves. Logistic regression was used to create a multivariate model to assess pre-procedural predictors of the primary outcome.A total of 96 patients underwent BMV during the study period. The primary outcome occurred in 36 patients during 12-year follow-up: 1 (1%) patient underwent re-BMV, 28 (29%) had MVR, and 8 (8%) died. Overall event-free survival was 62% at 12 years. On multivariate analysis, pre-procedural left atrial volume index (LAVI)80 mL/m² had a significant independent influence on event-free survival, as did previous mitral valve procedure and systolic pulmonary arterial pressure above 50 mmHg.Despite being a relatively low-volume center, excellent short and long-term results were demonstrated, with event-free survival rates consistent with previous studies from high-volume centers. LAVI independently predicted long-term event-free survival.

Aims This study evaluated the impact of serum uric acid (sUA) on the accuracy of pooled cohort equations (PCE) model, Systematic COronary Risk Evaluation 2 (SCORE2), and SCORE2-older persons. Methods and results We evaluated 19 769 asymptomatic self-referred adults aged 40–79 years free of cardiovascular disease and diabetes who were screened annually in a preventive healthcare setting. sUA levels were expressed as a continuous as well as a dichotomous variable (upper sex-specific tertiles defined as high sUA). The primary endpoint was the composite of death, acute coronary syndrome, or stroke, after excluding subjects diagnosed with metastatic cancer during follow-up. Mean age was 50 ± 8 years and 69% were men. During the median follow-up of 6 years, 1658 (8%) subjects reached the study endpoint. PCE, SCORE2, and high sUA were independently associated with the study endpoint in a multivariable model (P < 0.001 for all). Continuous net reclassification improvement analysis showed a 13% improvement in the accuracy of classification when high sUA was added to either PCE or SCORE2 model (P < 0.001 for both). sUA remained independently associated with the study endpoint among normal-weight subjects in the SCORE2 model (HR 1.3, 95% CI 1.1–1.6) but not among overweight individuals (P for interaction = 0.01). Subgroup analysis resulted in a significant 16–20% improvement in the model performance among normal-weight and low-risk subjects (P < 0.001 for PCE; P = 0.026 and P < 0.001 for SCORE2, respectively). Conclusion sUA significantly improves the classification accuracy of PCE and SCORE2 models. This effect is especially pronounced among normal-weight and low-risk subjects.

Patients with rapidly deteriorating clinical status due to severe aortic stenosis are often referred for expedited transcatheter aortic valve replacement (TAVR). Data regarding the outcome of such interventions is limited. We aimed to evaluate the outcome of patients undergoing expedited TAVR.Data were derived from the Israeli Multicenter Registry.Subjects were divided into two groups based on procedure urgency: patients who were electively hospitalized for the procedure (N = 3140) and those who had an expedited TAVR (N = 142). Procedural and periprocedural complication rates were significantly higher among patients with an expedited indication for TAVR compared to those having an elective procedure: valve malposition 4.6% versus 0.6% (p lt; 0.001), procedural cardiopulmonary resuscitation 4.3% versus 1.0% (p = 0.007), postprocedure myocardial infarction 2.0% versus 0.4% (p = 0.002), and stage 3 acute kidney injury 3.0% versus 1.1%, (p lt; 0.001). Patients with expedited indication for TAVR had significantly higher in hospital mortality (5.6% vs. 1.4%, p = 0.003). Kaplan-Meier's survival analysis showed that patients undergoing expedited TAVR had higher 3-year mortality rates compared to patients undergoing an elective TAVR procedure (p lt; 0.001). Multivariate analysis found that patients with expedited indication had fourfolds increased risk of in-hospital mortality (odds ratio: 4.07, p = 0.001), and nearly twofolds increased risk of mortality at 3-year (hazard ratio: 1.69, p = 0.001) compared to those having an elective procedure.Patients with expedited indications for TAVR suffer from poor short- and long-term outcomes. It is important to characterize and identify these patients before the deterioration to perform TAVR in a fast-track pathway to minimize their procedural risk.

Contains fulltext : 283507.pdf (Publisher’s version ) (Open Access) Background: Data to support the routine use of embolic protection devices for stroke prevention during transcatheter aortic valve replacement (TAVR) are controversial. Identifying patients at high risk for peri-procedural cerebrovascular events may facilitate effective patient selection for embolic protection devices during TAVR. Aim: To generate a risk score model for stratifying TAVR patients according to peri-procedural cerebrovascular events risk. Methods and results: A total of 8779 TAVR patients from 12 centers worldwide were included. Peri-procedural cerebrovascular events were defined as an ischemic stroke or a transient ischemic attack occurring ≤24 h from TAVR. The peri-procedural cerebrovascular events rate was 1.4% (n = 127), which was independently associated with 1-year mortality (hazards ratio (HR) 1.78, 95% confidence interval (CI) 1.06-2.98, p < 0.028). The TASK risk score parameters were history of stroke, use of a non-balloon expandable valve, chronic kidney disease, and peripheral vascular disease, and each parameter was assigned one point. Each one-point increment was associated with a significant increase in peri-procedural cerebrovascular events risk (OR 1.96, 95% CI 1.56-2.45, p < 0.001). The TASK score was dichotomized into very-low, low, intermediate, and high (0, 1, 2, 3-4 points, respectively). The high-risk TASK score group (OR 5.4, 95% CI 2.06-14.16, p = 0.001) was associated with a significantly higher risk of peri-procedural cerebrovascular events compared with the low TASK score group. Conclusions: The proposed novel TASK risk score may assist in the pre-procedural risk stratification of TAVR patients for peri-procedural cerebrovascular events.

Aims Most patients with significant (defined as ≥ moderate) tricuspid regurgitation (TR) are treated conservatively. Individual mortality rates are markedly variable. We developed a risk score based on comprehensive clinical and echocardiographic evaluation, predicting mortality on an individual patient level. Methods and results The cohort included 1701 consecutive patients with significant TR, half with isolated TR, admitted to a single hospital, treated conservatively. We derived a scoring system predicting 1-year mortality and validated it using k-fold cross-validation and with external validation on another cohort of 5141 patients. Score utility was compared with matched patients without significant TR. One-year mortality rate was 31.3%. The risk score ranged 0–17 points and included 11 parameters: age (0–3), body mass index ≤ 25 (0–1), history of liver disease (0–2), history of chronic lung disease (0–2), estimated glomerular filtration rate (0–5), haemoglobin (0–2), left-ventricular ejection fraction (0–1), right-ventricular dysfunction (0–1), right atrial pressure (0–2), stroke volume index (SVI) (0–1) and left-ventricular end-diastolic diameter (0–1). One-year mortality rates increased from 0 to 100%, as the score increased up to ≥16. Areas under the receiver operating curves were 0.78, 0.70, and 0.73, for the original, external validation, and external validation with SVI measured cohorts. The score remained valid in subpopulations of patients with quantified RV function, quantified TR and isolated TR. Significant TR compared to no TR, affected 1-year mortality stronger with higher scores, with a significantly positive interaction term. Conclusion We suggest a robust risk score for inpatients with significant TR, assisting risk stratification and decision-making. Our findings underscore the burden of TR providing benchmarks for clinical trial design.

Aims To evaluate the effect of an intercurrent non-coronary illness on the management and outcome of patients with non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results Consecutive hospitalized patients with a primary diagnosis of NSTEMI between August 2008 and December 2019 at Sheba Medical Center. All patients’ records were reviewed for the presence of a non-coronary precipitating event (NCPE): a major intercurrent acute non-coronary illness or condition, either cardiac or non-cardiac. The primary outcome was all-cause mortality. Cox regression with interaction analysis was applied. Final study population comprised 6491 patients, of whom 2621 (40%) had NCPEs. Patients with NCPEs were older (77 vs. 69 years) and more likely to have comorbidities. The most prevalent event was infection (35%, n = 922). During a median follow-up of 30 months, 2529 patients died. Patients with NCPEs were 43% more likely to die during follow-up in a multivariable model (95% CI: 1.31–1.55). Invasive strategy was associated with a 55% lower mortality among patients without NCPE and only 44% among patients with NCPE (P for interaction < 0.001). Dual antiplatelet therapy (DAPT) was associated with a 20% lower mortality in patients without NCEP and a non-significant mortality difference among patients with NCPE (P for interaction = 0.014). Sub-analysis by the specific NCPE showed the highest mortality risk among patients with infectious precipitant. The lower mortality associated with invasive strategy was not observed in this subgroup. Conclusion Among NSTEMI patients, the presence of an NCPE is associated with poor survival and modifies the effect of management strategies.

Mesenteric ischemia is a rare but lethal complication of transcatheter aortic valve replacement (TAVR). We present a challenging case of an 80-year-old man who had abdominal pain few hours following TAVR. Repeated abdominal and pelvic imaging showed no vascular obstruction, but exploratory laparoscopy revealed a necrotic bowel. (Level of Difficulty: Intermediate.), Graphical abstract

BackgroundSince the beginning of the coronavirus disease 2019 (COVID-19) pandemic in 2019, several countries have reported a substantial drop in the number of patients admitted with non-ST-segment myocardial infarction (NSTEMI).ObjectiveWe aimed to evaluate the changes in admissions, in-hospital management and outcomes of patients with NSTEMI in the COVID-19 era in a nationwide survey.MethodA prospective, multicenter, observational, nationwide study involving 13 medical centers across Israel aimed to evaluate consecutive patients with NSTEMI admitted to intensive cardiac care units over an 8-week period during the COVID-19 outbreak and to compare them with NSTEMI patients admitted at the same period 2 years earlier (control period).ResultsThere were 624 (43%) NSTEMI patients, of whom 349 (56%) were hospitalized during the COVID-19 era and 275 (44%) during the control period. There were no significant differences in age, gender and other baseline characteristics between the two study periods. During the COVID-19 era, more patients arrived at the hospital via an emergency medical system compared with the control period (P = 0.05). Time from symptom onset to hospital admission was longer in the COVID-19 era as compared with the control period [11.5 h (interquartile range, IQR, 2.5–46.7) vs. 2.9 h (IQR 1.7–6.8), respectively, P ConclusionIn contrast to previous reports, admission rates of NSTEMI were similar in this nationwide survey during the COVID-19 era. With longer time from symptoms to admission, but with the same time from hospital admission to reperfusion therapy and with similar in-hospital and 30-day mortality rates. Even in times of crisis, adherence of medical systems to clinical practice guidelines ensures the preservation of good clinical outcomes.

Background: Conscious sedation (CS) has been used successfully to treat patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) and as such is considered the standard anesthesia method. The local anesthesia (LA) only approach may be feasible and safe thanks to improvements in operators’ experience. Objective: To evaluate differences between LA only versus CS approaches on short- and long-term outcomes among patients undergoing TAVI. Methods: We performed a propensity score analysis on 1096 patients undergoing TAVI for severe AS. Two hundred and seventy-four patients in the LA group were matched in a ratio of 1:3 with 822 patients in the CS group. The primary outcome was a 1-year mortality rate. Secondary outcomes included procedural and peri-procedural complication rates and in-hospital mortality. Results: Patients in the CS group had significantly higher rates of grade 2–3 acute kidney injury and were more likely to have had new left bundle branch block and high-degree atrioventricular block. Patients who underwent TAVI under CS had significantly higher in-hospital and 1-year mortality rates compared to LA (1.6% vs. 0.0% p-value = 0.036 and 8.5% vs. 3.3% p-value = 0.004, respectively). Kaplan–Meier’s survival analysis showed that the cumulative probability of 1-year mortality was significantly higher among subjects undergoing CS compared to patients LA (p-value log-rank = 0.024). Regression analysis indicated that patients undergoing CS were twice more likely to die of at 1-year when compared to patients under LA (HR 2.18, 95%CI 1.09–4.36, p-value = 0.028). Conclusions: As compared to CS, the LA-only approach is associated with lower rates of peri-procedural complications and 1-year mortality rates.

The Medtronic Evolut Pro valve (EPV) is a new-generation self-expanding valve (SEV), particularly designed to reduce paravalvular leak (PVL) rates in transcatheter aortic valve replacement (TAVR). We aimed to compare the safety and efficacy of EPV with older-generation SEVs, in particular, postprocedural PVL and permanent pacemaker (PPM) implantation rates.We performed a retrospective, multicenter, propensity-matched analysis of the Israeli TAVR registry between September 2008 and June 2019. Two independent propensity score-matched comparisons were performed comparing EPV with the first-generation CoreValve (CV), and comparing EPV with the second-generation Evolut R valve (ERV).The registry included 2591 patients who were propensity-matched into 3 cohorts: EPV (n = 222), CV (n = 212), and ERV (n = 213). Moderate and above PVL rates were lower for EPV (angiographic PVL [aPVL], 0.6%; echocardiographic PVL [ePVL], 3.0%) as compared with CV (aPVL, 7.8% [P.001] and ePVL, 11.6% [P.01]), but not as compared with ERV (aPVL, 6.4% [P.01] and ePVL, 4.4% [P=.57]). Lower rates of PPM were noted for EPV (16.3%) as compared with both CV (33.5%; P.001) and ERV (24.4%; hazard ratio, 0.61; 95% confidence interval, 0.37-0.995; P=.046). Other safety and efficacy outcome rates were excellent, with significant improvements as compared with older-generation SEVs.The EPV demonstrates excellent procedural safety and efficacy outcomes. Moderate and above PVL rates were significantly reduced in comparison with CV; however, not significantly reduced as compared with ERV. The need for PPM implantation was lower as compared with both older-generation valves.

Aims To estimate the prevalence, incidence, mortality, and risk factors for atrial fibrillation (AF) in 195 countries and territories from 1990 to 2017. Methods and results Following the methodologies used in the Global Burden of Disease Study 2017, the prevalence, incidence, and mortality of AF were analysed by age, sex, year, socio-demographic index (SDI), and location. The percentage contributions of major risk factors to age-standardized AF deaths were measured by population attributable fractions. In 2017, there were 37.57 million [95% uncertainty interval (UI) 32.55–42.59] prevalent cases and 3.05 million (95% UI 2.61–3.51) incident cases of AF globally, contributing to 287 241 (95% UI 276 355–304 759) deaths. The age-standardized rates of prevalent cases, incident cases, and deaths of AF in 2017 and their temporal trends from 1990 to 2017 varied significantly by SDI quintile and location. High systolic blood pressure was the leading risk factor for AF age-standardized deaths [34.3% (95% UI 27.4–41.5)] in 2017, followed by high body mass index [20.7% (95% UI 11.5–32.2)] and alcohol use [9.4% (95% UI 7.0–12.2)]. Conclusion Our study has systematically and globally assessed the temporal trends of AF, which remains a major public heath challenge. Although AF mainly occurred in developed countries, the unfavourable trend in countries with lower SDI also deserves particular attention. More effective prevention and treatment strategies aimed at counteracting the increase in AF burden should be established in some countries.

We aimed to validate a new scoring system based on extent of cardiac damage for risk stratification in patients undergoing transcatheter aortic valve replacement (TAVR) in a real-world cohort and to examine the addition of baseline albumin in risk assessment.We investigated 2608 patients undergoing TAVR. Subjects were divided into five groups based on their echocardiography findings. Patients were further assessed by incorporating baseline albumin. Multivariable analysis demonstrated that each increase in stage was associated with significant increased risk of 1-year mortality (HR 1.37, 95%CI 1.23-1.54, p .001). Among patients at increased stage (3-4), incorporation of baseline of albumin identified the highest risk group, such that each 1 decrement in albumin levels was associated with more than triple increase in mortality among patients at stage 3 and 4 (HR 2.77, 95% CI 1.48-5.18, p-value = .001).Cardiac damage classification is validated in a real-world cohort of patients undergoing TAVR. Incorporation of low baseline albumin may further identify patients at the highest risk group.We evaluated 2608 patients undergoing transcatheter aortic valve replacement (TAVR) in order to validate a new scoring system dividing patients in to 5 stages (0-4) based on extent of cardiac damage. Patients were further assessed by incorporating baseline albumin. Multivariable analysis demonstrated that each increase in stage was associated with significant increased risk of 1-year mortality. Furthermore, among patients at increased stage (3-4), incorporation of baseline of albumin identified the highest risk group, such that each 1 decrement in albumin levels was associated with more than triple increase in mortality among patients at stage 3 and 4.

Background In contrast to surgical aortic valve replacement, left ventricle (LV) hypertrophy (LVH) had not been clearly associated with mortality following transcatheter aortic valve replacement (TAVR). Methods We performed a retrospective analysis of patients enrolled in the Israeli multicenter TAVR registry for whom preprocedural LV mass index (LVMI) data were available. Patients were divided into categories according to LVMI: normal LVMI and mild, moderate, and severe LVH. Mild LVH was regarded as the reference group. Additionally, LV geometry patterns were examined (concentric and eccentric LVH, and concentric remodeling). Results The cohort consisted of 1,559 patients, 46.5% male, with a mean age of 82.2 (±6.8) years and mean LVMI of 121 (±29) g/m2. Rates of normal LVMI and mild, moderate, and severe LVH were 31% (n = 485), 21% (n = 322), 18% (n = 279), and 30% (n = 475), respectively. Three-year mortality rates for normal LVMI and mild, moderate, and severe LVH were 19.8%, 18.3%, 23.7%, and 24.4%, respectively. Compared to mild LVH, moderate LVH and severe LVH were independently associated with an increased risk for all-cause mortality (hazard ratio [HR] 1.58, 95% CI 1.15-2.18, P = .005; HR 1.46, 95% CI 1.1-1.95, P = .009; respectively). Concentric LVH was independently associated with a decreased risk for mortality compared to normal LV geometry (HR 0.75, 95% CI 0.63-0.89, P = .001). Compared to concentric LVH, eccentric LVH was independently associated with a 33% increased risk for mortality (HR 1.33, 95% CI 1.11-1.60, P = .002). Conclusions Mild concentric LVH confers a protective effect among patients with severe aortic stenosis undergoing TAVR. However, hypertrophy becomes maladaptive, and an increased baseline LVMI, eccentric pattern particularly, may be associated with all-cause mortality in this population.

Background Vascular complications during transcatheter aortic valve replacement (TAVR) still pose a significant concern regarding procedural safety. Designated closure devices for large-bore vascular access are needed. Methods Patients undergoing TAVR were prospectively enrolled into the study. The InSeal vascular closure device (VCD) achieves hemostasis by utilizing a crescent-shaped nitinol scaffold covered by a biodegradable membrane, which is delivered at the arterial puncture site. The coprimary endpoints were predefined as hemostasis within 15 min following vessel access site closure and after activated clotting time falls below 200 s and the rate of related major vascular adverse events in first month. Results A total of 50 patients were prospectively enrolled into the study, with an average age of 80.8 ± 7.4 years and 62% males. Hemostasis with the Inseal VCD was achieved in 94% of the patients with average time-to-hemostasis of 51 ± 97 s. The rates of in-hospital vascular complications were 12% mostly driven by minor vascular complications (10%). Femoral artery stents were used in three patients due to failed hemostasis. Conclusions Initial clinical experience indicates that a novel, nitinol-based, large-bore vascular closure device is safe and effective in achieving hemostasis after TAVR.

Current guidelines suggest that an early invasive strategy should be considered for the treatment of non-ST-segment elevation myocardial infarction (NSTEMI). Although chronic kidney disease (CKD) is common among NSTEMI patients, these patients are under-represented in clinical trials, and data regarding their management are limited.The authors sought to evaluate the association between early invasive strategy and long-term survival among patients with NSTEMI and CKD.This was a retrospective analysis of 7,107 consecutive NSTEMI patients between 2008 and 2021. Patients were dichotomized into early (≤24 hours) and delayed invasive groups and stratified by kidney function. Inverse probability treatment weighting was used to adjust for differences in baseline characteristics. The primary outcome was all-cause mortality.The final study population comprised 3,529 invasively treated patients with a median age of 66 years (IQR: 58-74 years), 1,837 (52%) of whom were treated early. There were 483 (14%) patients with at least moderate CKD (estimated glomerular filtration rate [eGFR] 45 mL/min/1.73 mAmong NSTEMI patients, the association of early invasive strategy with long-term survival is modified by CKD and was not observed in patients with eGFR 45 mL/min/1.73 m

The durability of the immune response following the 3-dose BNT162b2 vaccination is unknown. The complexity of the situation is enhanced by the threat that highly transmissible variants may further accelerate the decline in the protection afforded by mRNA vaccines.One hundred and three 3-dose-vaccinated heart transplant recipients were longitudinally assessed for the kinetics of variant-specific neutralization (Cohort 1, n = 60) and SARS-CoV-2-specific-T-cell response (Cohort 2, n = 54) over 6 months. Neutralization and T-cell responses were compared between paired samples at 2 time points, using the Kruskal-Wallis test followed by Dunn's multiple comparison test for continuous variables and McNemar's test for dichotomous variables. The Bonferroni method of p values adjustment for multiple comparison was applied.The third dose induced high neutralization of the wild-type virus and delta variant (geometric mean titer [GMT], 137.2 [95% CI, 84.8-221.9] and 80.6, [95% CI, 49.3-132.0], respectively), and to a lesser degree of the omicron variant (GMT, 10.3 [95% CI, 5.9-17.9]). At 6 months, serum neutralizing activity declined but was still high for the wild-type virus and for the delta variant (GMTs 38.1 [95% CI, 21.2-69.4], p = 0.011; and 28.9 [95% CI, 16.6-52.3], p = 0.022, respectively), but not for the omicron variant (GMT 5.9 [95% CI, 3.4-9.8], p = 0.463). The percentages of neutralizing sera against the wild-type virus, delta and omicron variants increased from 70%, 65%, and 38%, before the third dose, to 93% (p0.001), 88% (p0.001), and 48% (p = 0.021) at 3 weeks after, respectively; and remained high through the 6 months for the wild-type (80%, p = 0.06) and delta (77%, p = 0.102). The third dose induced the development of a sustained SARS-CoV-2-specific-T-cell population, which persisted through 6 months.The third BNT162b2 dose elicited a durable SARS-CoV-2-specific T-cell response and induced effective and durable neutralization of the wild-type virus and the delta variant, and to a lesser degree of the omicron variant.

Background: As transcatheter aortic valve (TAV) replacement is increasingly used in patients with longer life expectancy, a sizable proportion will require redo TAV replacement (TAVR). The unique configuration of balloon-expandable TAV (bTAV) vs a self-expanding TAV (sTAV) potentially affects TAV-in-TAV outcome. Objectives: The purpose of this study was to better inform prosthesis selection, TAV-in-TAV outcomes were assessed according to the type of initial and subsequent TAV. Methods: Patients from the Redo-TAVR registry were analyzed using propensity weighting according to their initial valve type (bTAV [n = 115] vs sTAV [n = 106]) and subsequent valve type (bTAV [n = 130] vs sTAV [n = 91]). Results: Patients with failed bTAVs presented later (vs sTAV) (4.9 ± 2.1 years vs 3.7 ± 2.3 years; P < 0.001), with smaller effective orifice area (1.0 ± 0.7 cm2 vs 1.3 ± 0.8 cm2; P = 0.018) and less frequent dominant regurgitation (16.2% vs 47.3%; P < 0.001). Mortality at 30 days was 2.3% (TAV-in-bTAV) vs 0% (TAV-in-sTAV) (P = 0.499) and 1.7% (bTAV-in-TAV) vs 1.0% (sTAV-in-TAV) (P = 0.612); procedural safety was 72.6% (TAV-in-bTAV) vs 71.2% (TAV-in-sTAV) (P = 0.817) and 73.2% (bTAV-in-TAV) vs 76.5% (sTAV-in-TAV) (P = 0.590). Device success was similar according to initial valve type but higher with subsequent sTAV vs bTAV (77.2% vs 64.3%; P = 0.045), primarily because of lower residual gradients (10.3 mm Hg [8.9-11.7 mm Hg] vs 15.2 mm Hg [13.2-17.1 mm Hg]; P < 0.001). Residual regurgitation (moderate or greater) was similar after bTAV-in-TAV and sTAV-in-TAV (5.7%) and nominally higher after TAV-in-bTAV (9.1%) vs TAV-in-sTAV (4.4%) (P = 0.176). Conclusions: In selected patients, no association was observed between TAV type and redo TAVR safety or mortality, yet subsequent sTAV was associated with higher device success because of lower redo gradients. These findings are preliminary, and more data are needed to guide valve choice for redo TAVR.

Conflicting data exist on the prognostic significance of permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR).The purpose of this study was to evaluate whether PPM implantation after TAVR is associated with adverse outcomes.A retrospective analysis of a cohort comprised patients enrolled in a prospective registry between 2008 and 2019. Participants were allocated into 3 groups: patients without a prior pacemaker (n = 930 [75%]), those with previous pacemaker implantation (n = 118 [10%]), and those with pacemaker implantation after TAVR (n = 191 [15%]). The primary outcome included death and heart failure hospitalizations at 1 year. Secondary outcomes included death and heart failure hospitalizations stratified by pacing burden.A total of 1239 patients underwent TAVR with a median follow-up period of 2.3 years (interquartile range 1-4 years). Patients with previous and new pacemaker implantation were older (84 [80-88], 84 [80-88], and 82 [78-86] years; P = .009) and had lower baseline left ventricular ejection fraction (50% ± 15%, 55% ± 12%, and 56% ± 12%; P.001). Patients who underwent new pacemaker implantation had higher combined outcome of death and heart failure hospitalizations (21%,12%, and 14%; P = .01). New pacemaker implantation was associated with almost twice the risk of 1-year mortality (odds ratio 1.85; 95% confidence interval 1.13-3.02; P = .014). Pacing burden, however, was not associated with the primary outcome. Furthermore, no significant difference was observed at long-term follow-up (cumulative probability to develop the primary end point at 3 years was 57% ± 2% [without PPM], 57% ± 6% [prior PPM], 54% ± 4% [new PPM]; P = .52).Pacemaker implantation after TAVR is associated with higher 1-year adverse outcome, but this attenuates over time, suggesting that competing factors may play a role. Interestingly, pacing burden is not associated with adverse clinical course.

Introduction Cardiorespiratory fitness (CRF) is associated with cardiovascular co-morbidities and is a strong predictor of adverse cardiovascular outcomes. However, data on the natural history of cardiorespiratory fitness among healthy subjects is limited. Purpose This study investigated what are the predictors of deterioration in CRF over time. Methods We investigated 36,239 men and women who were annually screened in a tertiary medical center and completed an exercise stress test in all visits, with a total of 175,596 annual visits. Subjects who failed to complete maximal exercise stress test according to the Bruce protocol at their first baseline visit were excluded. In addition, subjects with less than five visits to the center or those who developed ischemic heart disease during follow-up were excluded. Fitness was categorized into age- and sex-specific quintiles (Q) according to Bruce protocol treadmill time. Change in CRF between the first baseline visit and the fifth visit was used to calculate fitness deterioration. The primary study endpoint was defined as the lower sex-specific quintile of change in metabolic equivalents (METS) between visits 1 and 5. Logistic regression models were applied. Results Final study population included 10,841 subjects. The mean age of the study population was 49±10 years, the mean BMI was 26±4, and 8107 (75%) were men. Median METS at baseline were 10.8 (IQR 9–12.6) and 11.1 (IQR 9.4–13) at the first and fifth visit, respectively (p Conclusion Obesity is an independent predictor of future CRF deterioration. The effect of obesity on future CRF deterioration is more pronounced among women as compared to men. Funding Acknowledgement Type of funding sources: None.

Introduction The relationship between ischemic heart disease (IHD) and advanced chronic kidney disease is well established. However, there is a paucity of data regarding the long-term association in between renal function and incidence of IHD. Purpose To study the remote association between point renal function and future incidence of ischemic heart disease among healthy adults. Methods We evaluated asymptomatic self-referred adults who participated in a medical screening program. All subjects were free of IHD at baseline. Glomerular Filtration Rate (GFR) was calculated by CKD-EPI and divided into quartiles (Q1 represents the lowest quartile). Study endpoint was the development of IHD which was externally adjudicated by a physician. Mortality data were available for all subjects from national registry. Cox regression models were applied while adjusting for confounders. Results The final study population included 27,647 subjects (68% men) with a mean age of 47 years. At baseline (first screening visit), median GFR by CKD-EPI was 84 [IQR 74; 95] and 86 [IQR 74.; 101] mL/min per 1.73m2 for men women, respectively. During median follow up of 6 years [IQR 2; 12], 2,286 (8%) of subjects developed IHD, of whom 1,912 (10%) were men and 374 (4%) were women. Incident IHD was in 964 (13.98%), 705 (10.22%), 437 (6.34%) and 171 (2.48%) subjects from GFR Q1-Q4, respectively. Kaplan Meier survival analysis demonstrated a graded increased risk of IHD with decreasing eGFR quartiles (p Log rank Conclusion Mild renal dysfunction even within the normal range is independently associated with remote risk of IHD among young apparently healthy adults. Cardiovascular screening should be considered among young patients with reduced renal function, even within normal reference range. Funding Acknowledgement Type of funding sources: None. Figure 1

Background: A small proportion of patients in need of transcatheter aortic valve replacement (TAVR) are not suitable for the transfemoral approach due to peripheral artery disease. Alternative TAVR approaches are associated with short- and long-term hazards. A novel technique of caval-aortic (transcaval) access for TAVR has been utilized as an alternative access technique.Aim: To compare safety and efficacy of transcaval access as compared to other alternative access (axillary or apical) for TAVR.Methods: A single-center, retrospective analysis of consecutive patients undergoing alternative access for TAVR. Events were adjudicated according to VARC-2 criteria.Results: A total of 185 patients were included in the present analysis. Mean age was 81 years with a small majority for male gender (54%). Of the entire cohort, 20 patients (12%) underwent transcaval TAVR, and 165 patients (82%) underwent TAVR using alternative access. Overall, baseline characteristics were comparable between the two groups. General anesthesia was not utilized in transcaval patients; however, it was routinely used in nearly all alternative access patients. TAVR device success was comparable between the two groups (95%). Acute kidney injury occurred significantly less frequently among transcaval patients as compared to alternative access patients (5 vs. 12%, p = 0.05). Hospital stay was shorter for transcaval patients (6.3 days vs. 14.4; p < 0.001). No difference in early or 30-day mortality (10 vs. 7.9%, p = 0.74) was noted between groups.Conclusions: In patients who cannot undergo TAVR via the trans-femoral approach due to peripheral vascular disease, transcaval access is a safe approach as compared to other alternative access techniques, with lower risk of kidney injury and shorter hospital stay.

Transcatheter 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. We performed a retrospective study including patients with severe aortic stenosis (AS) and BAAS, measured by multidetector computed tomography (MDCT), undergoing TAVI with self-expandable (SE) or balloon-expandable (BE) THV from the Israeli multicenter TAVI registry. TAVI outcomes were assessed according to the Valve Academic Research Consortium-2 (VARC-2). Out 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 paravalvular leak (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 ± 3.7mmHg vs. 12.5 ± 7.2mmHg; 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. BAAS is common among patients undergoing TAVI. Selection of a larger THV in these patients is associated with lower rates of PVL and better hemodynamic profile in patients implanted with SE and BE-THV, respectively, with no effect on procedural complications.

BACKGROUND The repeated waves of the COVID-19 pandemic have highlighted the necessity to optimize vaccine responses in immunocompromised populations. We investigated the safety and immunogenicity of a third, booster, dose of the Pfizer BNT162b2 vaccine in heart transplant (HT) patients. METHODS The cohort comprised 96 adult HT patients who received a third homologous dose of the BNT162b2 vaccine 168 days after the second dose. The vaccine-induced antibody responses of both receptor-binding domain (RBD) IgG and neutralizing antibodies were assessed in all patients, with a positive antibody response being defined as the presence of either IgG anti-RBD or neutralizing antibodies. For a subset of patients, T cell response was also studied. RESULTS The third dose was associated with a low rate of adverse events, mostly mild pain at the injection site. No serious adverse events were recorded, and there were no episodes of rejection. At 18 days following the third dose of the vaccine, the positive antibody response increased from 23% to 67%, with a corresponding increase in neutralizing capacity. The third dose elicited SARS-CoV-2 neutralization titers >9-fold and IgG anti-RBD antibodies >3-fold of the range achieved after the two primary doses. Mycophenolate use, lower eGFR and higher C-reactive protein were independently associated with a reduced likelihood of generating an immune response. Importantly, a specific T-cell response following the third dose was evident in the majority of transplant recipients. CONCLUSIONS An homologous third booster dose of the BNT162b2 vaccine gave overall consistent tolerability and a good safety profile, while eliciting humoral and cellular immune responses.