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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.

Pulsed electric fields (PEFs) have emerged as an ideal cardiac ablation modality. At present numerous clinical trials in humans are exploring PEF as an ablation strategy for both atrial and ventricular arrhythmias, with early data showing significant promise. As this is a relatively new technology there is limited understanding of its principles and biophysics. Importantly, PEF biophysics and principles are starkly different to current energy modalities (radiofrequency and cryoballoon). Given the relatively novel nature of PEFs, this review aims to provide an understanding of the principles and biophysics of PEF ablation. The goal is to enhance academic research and ultimately enable optimization of ablation parameters to maximize procedure success and minimize risk.

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.

BackgroundAs indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults.MethodsA retrospective, pharmacovigilance study of the FDA’s global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (ResultsWe identified safety reports of 129,795 patients who received non-insulin anti-diabetic drugs (NIAD), including 24,253 who were treated with SGLT2i (median age 60 [IQR: 51–68] years, 2,339 [9.6%] aged ≥ 75 years). Compared to other NIAD, SGLT2i were significantly associated with amputations (adj.ROR = 355.1 [95%CI: 258.8 − 487.3] vs adj.ROR = 250.2 [79.3 − 789.5]), Fournier gangrene (adj.ROR = 45.0 [34.5 − 58.8] vs adj.ROR = 88.0 [27.0 − 286.6]), diabetic ketoacidosis (adj.ROR = 32.3 [30.0 − 34.8] vs adj.ROR = 23.3 [19.2 − 28.3]), genitourinary infections (adj.ROR = 10.3 [9.4 − 11.2] vs adj.ROR = 8.6 [7.2 − 10.3]), nocturia (adj.ROR = 5.5 [3.7 − 8.2] vs adj.ROR = 6.7 [2.8 − 15.7]), dehydration (adj.ROR = 2.5 [2.3 − 2.8] vs adj.ROR = 2.6 [2.1 − 3.3]), and fractures (adj.ROR = 1.7 [1.4 − 2.1] vs adj.ROR = 1.5 [1.02 − 2.1]) in both adults and older adults, respectively. None of these safety signals was significantly greater in older adults (Pinteractionthreshold of 0.05). Acute kidney injury was associated with SGLT2i in adults (adj.ROR = 1.97 [1.85 − 2.09]) but not in older adults (adj.ROR = 0.71 [0.59 − 0.84]). Falls, hypotension, and syncope were not associated with SGLT2i among either adults or older adults.ConclusionIn this global post-marketing study, none of the adverse events was reported more frequently among older adults. Our findings provide reassurance regarding SGLT2i treatment in older adults, although careful monitoring is warranted.

Background: Previous animal studies have shown no significant vascular injury from pulsed electrical field (PEF) ablation. We sought to assess the effect of PEF on swine coronary arteries. Methods: We performed intracoronary and epicardial (near the coronary artery) PEF ablations in swine pretreated with dual antiplatelet and antiarrhythmic therapy. Intracoronary PEF was delivered using MapiT catheters (Biotronik, Berlin), whereas epicardial PEF was delivered using EPT catheters (Boston Scientific, MA). PEF pulse duration was microseconds (Nanoknife 3.0, Angio Dynamics, NY) or nanoseconds (CellFX, Pulse Biosciences, CA). Results: We performed 39 intracoronary ablations in 10 swine and 20 epicardial-pericoronary ablations in 4 separate swine. Intracoronary PEF was delivered at higher energy compared with epicardial PEF (46 [interquartile range, IQR 20–85] J versus 10 [IQR 10–11] J, P < 0.01). Reversible coronary spasm occurred in 49% intracoronary ablations and 45% epicardial ablations ( P =0.80). At the end study, fixed coronary stenosis was demonstrated in 44% intracoronary ablations (80% for microsecond PEF and 18% for nanosecond PEF) and 0% epicardial ablations. Visible hemorrhagic and/or fibrotic myocardial lesions were observed at necropsy with similar frequency between intracoronary and epicardial PEF (45% versus 50%, P =0.70). Nanosecond PEF (49 ablations in 11 swine), when compared with microsecond PEF (10 intracoronary ablations in 3 swine), resulted in lower energy delivery (21 [IQR 10–46] J versus 129 [IQR 24–143] J, P =0.03) and less incidence of fixed coronary stenosis (18% versus 80%, P =0.04). Conclusions: In the swine model, intracoronary PEF resulted both in significant coronary spasm and fixed coronary stenosis. Epicardial PEF, delivered at lower energy, resulted in reversible spasm but no fixed coronary stenosis.

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.

Data de publicació electrónica: 30-09-2022 BACKGROUND: Pulsed field ablation (PFA) is a novel non-thermal cardiac ablation technology based on irreversible electroporation. Unfortunately, the characteristics of the electric field waveforms used in clinical and experimental PFA are not typically reported. This study examines the effect of the frequency of biphasic waveforms and compares biphasic to monophasic waveforms. METHODS: A total of 29 Sprague-Dawley rats were treated with PFA using an epicardial monopolar electrode. Biphasic waveforms with three different frequencies, 90, 260 and 450 kHz (10 bursts of 100 µs duration at 500 V or 800 V) and monophasic waveforms (10 pulses of 100 µs duration at 500 V) were studied. Collateral neuromuscular stimulation and temperature increase in the point of application were directly measured. Lesion formation was assessed 3 weeks after treatment by histopathologic analysis. Computer simulations were used to estimate the electric field lethal threshold for each condition. A previous in vitro study was performed to draw a complete characterization of the studied dependencies. RESULTS: Morphometric analysis demonstrated a significant association between chronic lesion size and waveform characteristics. For the same voltage level, monophasic waveforms yielded the largest lesions compared to any of the biphasic protocols (p

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.

Objective: To investigate the association of voice analysis with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients and Methods: A vocal biomarker, a unitless scalar with a value between 0 and 1, was developed based on 434 voice samples. The biomarker training was followed by a prospective, multicenter, observational study. All subjects were tested for SARS-CoV-2, had their voice recorded to a smartphone application, and gave their informed consent to participate in the study. The association of SARS-CoV-2 infection with the vocal biomarker was evaluated. Results: The final study population included 80 subjects with a median age of 29 [range, 23 to 36] years, of whom 68% were men. Forty patients were positive for SARS-CoV-2. Infected patients were 12 times more likely to report at least one symptom (odds ratio, 11.8; P

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.

Mid-myocardial ventricular arrhythmias are challenging to treat. Cardiac electroporation via pulsed electric fields (PEFs) offers significant promise. We therefore tested PEF delivery using screw-in pacemaker leads as proof-of-concept.In 5 canine models, we applied nanosecond PEF (pulse width 300 ns) across the right ventricular (RV) septum using a single lead bipolar configuration (n = 2) and between two leads (n = 3). We recorded electrograms (EGMs) prior to, immediately post, and 5 min after PEF. Cardiac magnetic resonance imaging (cMRI) and histopathology were performed at 2 weeks and 1 month.Nanosecond PEF induced minimal extracardiac stimulation and frequent ventricular ectopy that terminated post-treatment; no canines died with PEF delivery. With 1 lead, energy delivery ranged from 0.64 to 7.28 J. Transient ST elevations were seen post-PEF. No myocardial delayed enhancement (MDE) was seen on cMRI. No lesions were noted on the RV septum at autopsy. With 2 leads, energy delivery ranged from 56.3 to 144.9 J. Persistent ST elevations and marked EGM amplitude decreases developed post-PEF. MDE was seen along the septum 2 weeks and 1 month post-PEF. There were discrete fibrotic lesions along the septum; pathology revealed dense connective tissue with 5% residual cardiomyocytes.Ventricular electroporation is feasible and safe with an active fixation device. Reversible changes were seen with lower energy PEF delivery, whereas durable lesions were created at higher energies. Central illustration: pulsed electric field delivery into ventricular myocardium with active fixation leads.

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.

Aims The aim of this study was to estimate the burden and risk factors for ischaemic heart disease (IHD) in 195 countries and territories from 1990 to 2017. Methods and results Data from the Global Burden of Disease Study 2017 were used. Prevalence, incidence, deaths, years lived with disability (YLDs), and years of life lost (YLLs) were metrics used to measure IHD burden. Population attributable fraction was used to estimate the proportion of IHD deaths attributable to potentially modifiable risk factors. Globally, in 2017, 126.5 million [95% uncertainty interval (UI) 118.6 to 134.7] people lived with IHD and 10.6 million (95% UI 9.6 to 11.8) new IHD cases occurred, resulting in 8.9 million (95% UI 8.8 to 9.1) deaths, 5.3 million (95% UI 3.7 to 7.2) YLDs, and 165.0 million (95% UI 162.2 to 168.6) YLLs. Between 1990 and 2017, despite the decrease in age-standardized rates, the global numbers of these burden metrics of IHD have significantly increased. The burden of IHD in 2017 and its temporal trends from 1990 to 2017 varied widely by geographic location. Among all potentially modifiable risk factors, age-standardized IHD deaths worldwide were primarily attributable to dietary risks, high systolic blood pressure, high LDL cholesterol, high fasting plasma glucose, tobacco use, and high body mass index in 2017. Conclusion Our results suggested that IHD remains a major public health challenge worldwide. More effective and targeted strategies aimed at implementing cost-effective interventions and addressing modifiable risk factors are urgently needed, particularly in geographies with high or increasing burden.

Primary graft dysfunction (PGD) is a leading cause of early morbidity and mortality after heart transplantation (HT). Statins are known to have immunomodulatory and antiinflammatory effects, and perioperative statin therapy has been associated with reduced cardiovascular complications and improved outcomes after cardiac and noncardiac surgery. Thus, we investigated the influence on PGD of statin therapy administered to recipients before HT.A retrospective cohort study was conducted on 275 HT recipients assessed from 1997 to 2017; 167 (61%) had received statins during the month prior to and at time of transplantation, whereas 108 (39%) had not. Endpoints included PGD (defined according to the International Society of Heart and Lung Transplantation consensus statement), in-hospital mortality, and 1-year and 5-year survival.PGD incidence was significantly lower for statin-treated patients (21 vs 60%, P.001). Multivariable analysis demonstrated that pre-HT statin therapy was independently associated with a significant 65% reduced risk for PGD and a 73% reduced risk for in-hospital mortality. One- and five-year mortality, adjusted for age, sex, and amiodarone therapy, were significantly lower for recipients treated with statins (hazard ratio 0.33 and 0.39, 95% confidence interval 0.17-0.63 and 0.22-0.68, respectively; P = .001).Pre-HT statin therapy was independently associated with a reduced risk for PGD and mortality. Our results also suggested that statins have a beneficial prognostic impact on heart failure patients awaiting HT.

Norton scoring system is used to assess frailty of hospitalized patients with various medical conditions. We aimed to evaluate whether admission Norton scoring system predicts adverse outcomes among heart failure patients.The study population comprised 4388 acute heart failure patients between the years 2008 and 2017. Patients were allocated to 3 groups according to their admission Norton score [(≤15-low, 16-18-intermediate, and ≥19-high)]. Primary outcome included all-cause mortality at 30, 90 days, and 1 year. Multivariate Cox proportional hazards regression modeling was used to assess the independent association between Norton score and mortality. Net reclassification improvement (NRI) analysis was used to asses Norton's additive predictive ability upon known prognostic factors.Among 4388 study patients, 32% (n=1611) had low Norton score, 28% (n=1384) intermediate score, and 40% (n=1900) high score. Kaplan-Meier analysis demonstrated significantly higher 30-day mortality among patients with a low Norton score as compared with those with intermediate or high score (2.6%, 6.3%, and 16.1%; log rank p0.001). A similar trend was noted at 90 days and 1 year. Multivariate analysis found Norton score to be an independent predictor of mortality with each one-point decrement associated with a significant 15% increased risk for 30-day mortality [HR=1.15 (95%CI, 1.12-1.17) p0.001]. NRI analysis showed an improvement of 21.5% (95%CI 18.3-25.1%) predicting 1-year mortality.Our findings show that the admission Norton score is a powerful marker of short- and long-term mortality. These data suggest that the scale should be added as a risk stratification tool in this high-risk population.

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.

Aims Data on the association of cardiorespiratory fitness with survival of cancer patients are limited. This study aimed to evaluate the association between midlife cardiorespiratory fitness and survival after a subsequent cancer diagnosis. Methods We evaluated 19,134 asymptomatic self-referred adults who were screened in preventive healthcare settings. All subjects were free of cardiovascular disease and cancer at baseline and completed a maximal exercise stress test. Fitness was categorised into age-specific and sex-specific quintiles according to the treadmill time and dichotomised to low (quintiles 1–2) and high fitness groups. Results The mean age was 50 ± 8 years and 72% were men. During a median follow-up of 13 years (interquartile range 7–16) 517 (3%) died. Overall, 1455 (7.6%) subjects developed cancer with a median time to cancer diagnosis of 6.4 years (interquartile range 3–10). Death from the time of cancer diagnosis was significantly lower among the high fitness group (Plog rank = 0.03). Time-dependent analysis showed that subjects who developed cancer during follow-up were more likely to die (P Conclusion Higher midlife cardiorespiratory fitness is associated with better survival among cancer patients. Our findings support fitness assessment in preventive healthcare settings.

Hypomagnesemia is commonly observed in heart transplant (HT) recipients receiving calcineurin inhibitors. Since low serum magnesium (s-Mg) has been implicated in the progression of atherosclerosis, potentially leading to worsening coronary heart disease, arrhythmias and sudden death, we investigated the association between s-Mg and HT outcomes. Between 2002 and 2017, 150 HT patients assessed for s-Mg were divided into high (≥1.7 mg/dL) and low s-Mg groups according to the median value of all s-Mg levels recorded during the first 3 months post-HT. Endpoints included survival, cardiac allograft vasculopathy (CAV), any-treated rejection (ATR) and NF-MACE. Kaplan-Meier analysis showed that at 15 years after HT, both survival (76 vs 33%, log-rank p = 0.007) and freedom from CAV (75 vs 48%, log-rank p = 0.01) were higher in the high versus low s-Mg group. There were no significant differences in freedom from NF-MACE or ATR. Multivariate analyses consistently demonstrated that low s-Mg was independently associated with a significant 2.6-fold increased risk of mortality and 4-fold increased risk of CAV (95%CI 1.06 to 6.4, p = 0.04; 95%CI 1.12 to 14.42, p = 0.01, respectively). In conclusion, low s-Mg is independently associated with increased mortality and CAV in HT patients. Larger multi-center prospective studies are needed to confirm these findings and to examine the effect of Mg supplementation.

Background: Reducing door-to-balloon time may not reduce mortality, but reducing the time from symptom onset to first medical contact (FMC) may alone improve patient outcomes. The purpose of this s...

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.

BackgroundLeft ventricular assist devices (LVADs) may reverse elevated pulmonary vascular resistance (PVR) which is associated with worse prognosis in heart failure (HF) patients. We aim to describe the temporal changes in hemodynamic parameters before and after LVAD implantation among patients with or without elevated PVR.MethodsHF patients who received continuous-flow LVAD (HeartMate 2&3) at a tertiary medical center and underwent right heart catheterization with PVR reversibility study before and after LVAD surgery. Patients were divided into 3 groups: normal PVR (ResultsOverall, 85 LVAD patients with a mean age of 58 years (IQR 49–64), 65 patients (76%) were male; 60 patients had normal PVR, 20 patients with reversible and 5 patients with non-reversible PVR pre-LVAD. All patients with elevated PVR (≥4WU) had higher pulmonary pressures (PP) and increased trans-pulmonary gradient (TPG) compared to patients with normal PVR (p < 0.05). Patients with non-reversible PVR were more likely to have a significantly lower baseline cardiac output (CO) compared to all other groups (p ≤ 0.02). Hemodynamic parameters and PVR post LVAD were similar in all study groups. Patients with baseline elevated PVR (reversible and non-reversible) demonstrated a significant improvement in PP and TPG compared to patients with normal baseline PVR (p ≤ 0.05). The improvement in CO and PVR post-LVAD in the non-reversible PVR group was significantly greater compared to all other groups (p < 0.01). There were no significant differences between study groups in post LVAD and post heart transplantation course.ConclusionHemodynamic parameters improved after LVAD implantation, regardless of baseline PVR and reversibility, and enabled heart transplantation in patients who were ineligible due to non-reversible elevated PVR. Our findings suggest that mitigation of elevated non-reversible PVR is related to reduction in PP and increase in CO.

Background Despite optimized medical management and techniques of primary percutaneous coronary intervention, a substantial proportion of patients with ST‐segment–elevation myocardial infarction (STEMI) display significant microvascular damage. Thrombotic microvascular obstruction (MVO) has been implicated in the pathogenesis of microvascular and subsequent myocardial damage attributed to distal embolization and microvascular platelet plugging. However, there are only scarce data regarding the effect of platelet reactivity on MVO. Methods and Results We prospectively evaluated 105 patients in 2 distinct periods (2012–2013 and 2016–2018) who presented with first ST‐segment–elevation myocardial infarction and underwent primary percutaneous coronary intervention. All patients were treated with dual antiplatelet therapy (DAPT). Blood samples were analyzed for platelet reactivity, and cardiac magnetic resonance imaging scans were evaluated for late gadolinium enhancement and MVO. DAPT suboptimal response was defined as hyporesponsiveness to either aspirin or P2Y12 receptor inhibitor agents and demonstrated in 31 patients (29.5%) of the current cohort. Suboptimal platelet response to DAPT was associated with a significantly greater extent of MVO when expressed as a percentage of the left ventricular mass, left ventricular scar, and the number of myocardial left ventricular segments showing MVO ( P P P =0.01). Patients with a greater extent of MVO were more likely to sustain major adverse cardiovascular events at a 1‐year follow‐up (37% versus 11%; P Conclusions In patients undergoing primary percutaneous coronary intervention for ST‐segment–elevation myocardial infarction, platelet reactivity in response to DAPT is a key predictor of the extent of both myocardial and microvascular damage.

Pulsed electric field (PEF) ablation is an emerging modality for the treatment of cardiac arrhythmias. Data regarding effects on the interventricular septum are limited, and the optimal delivery protocol and electrode configuration remain undefined.This study sought to evaluate the electrophysiological, imaging, and histological characteristics of bipolar direct-current PEF delivered across the interventricular septum.PEF was applied between identical solid-tip ablation catheters positioned on either side of the septum in a chronic canine model. Intracardiac and surface electrophysiological data were recorded following delivery. In 4 animals, cardiac magnetic resonance (CMR) was performed early (6 ± 2 days) and late (30 ± 2 days) postablation. After 4 weeks of survival, cardiac specimens were sectioned for histopathological analysis.In 8 canines, PEF was delivered in 27 separate septal sites (45 ± 17 J/site) with either microsecond or nanosecond PEF. Acute complications included transient complete atrioventricular block in 5 animals (63%) after delivery at the anterobasal septum, with right bundle branch block persisting in 3 (38%). Ventricular fibrillation occurred in 1 animal during microsecond but not nanosecond PEF. Postprocedural CMR showed prominent edema and significant left ventricular systolic dysfunction, which recovered with late imaging. At 4 weeks, 36 individual well-demarcated lesions were demonstrated by CMR and histopathology. Lesion depth measured by histology was 2.6 ± 2.1 mm (maximum 10.9 mm and near transmural).Bipolar PEF ablation of the interventricular septum is feasible and can produce near transmural lesions. Myocardial stunning, edema, and conduction system injury may occur transiently. Further studies are required to optimize safe delivery and efficacious lesions.

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

BackgroundDiastolic plateau is an invasive hemodynamic marker of impaired right ventricular (RV) diastolic filling. The purpose of the current analysis was to evaluate the prognostic importance of this sign in left ventricular assist device (LVAD) patients.MethodsThe analysis included all LVAD patients who received continuous-flow LVAD (HeartMate 3) at the Sheba medical center and underwent right heart catheterization (RHC) during follow up post-LVAD surgery. Patients were dichotomized into 2 mutually exclusive groups based on a plateau duration cutoff of 55% of diastole. The primary end point of the current analysis was the composite of death, heart transplantation, or increase in diuretic dosage in a 12-month follow-up period post-RHC.ResultsStudy cohort included 59 LVAD patients with a mean age of 57 (IQR 54–66) of whom 48 (81%) were males. RHC was performed at 303 ± 36 days after LVAD surgery. Patients with and without diastolic plateau had similar clinical, echocardiographic, and hemodynamic parameters. Kaplan–Meier survival analysis showed that the cumulative probability of event at 1 year was 65 ± 49% vs. 21 ± 42% for primary outcomes among patients with and without diastolic plateau (p Log rank < 0.05 for both). A multivariate model with adjustment for age, INTERMACS score and ischemic cardiomyopathy consistently showed that patients with diastolic plateau were 4 times more likely to meet the study composite end point (HR = 4.35, 95% CI 1.75–10.83, p = 0.002).ConclusionDiastolic plateau during RHC is a marker of adverse outcome among LVAD patients.

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.

Aims While genetic and biological studies indicated a potential association between proprotein-convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and hyperglycaemia, real-world data are limited. Therefore, we sought to investigate this association using the FDA adverse event reporting system (FAERS). Methods and results The FAERS database (2015–2020) was retrospectively queried to characterize reporting of hyperglycaemic adverse events (AEs) with PCSK9i. Disproportionality analyses were performed using the adjusted reporting odds ratio (adj.ROR), and the lower bound of the information component (IC) 95% credibility interval (IC025 > 0 is deemed significant). Among 7 295 624 eligible patients, 71 748 reports of evolocumab and 15 976 of alirocumab were identified. Compared to the full database, PCSK9i treatment was associated with increased reporting of hyperglycaemic AEs [n = 1841, adj.ROR = 1.14 (1.07–1.22), IC025 = 0.13]. Hyperglycaemic AEs were primarily mild hyperglycaemia [n = 1469, adj. ROR = 1.48 (1.36–1.62), IC025 = 0.51] rather than diabetes [n = 372, adj. ROR = 0.67 (0.60–0.74), IC025 = −0.90]. Among PCSK9i agents, evolocumab, but not alirocumab, was associated with hyperglycaemic AEs [n = 1587, adj. ROR = 1.24 (1.15–1.32), IC025 = 0.20; n = 254, adj. ROR = 0.73 (0.60–0.88), IC025 = −0.38, respectively]. Hyperglycaemic AEs were reported more often with PCSK9i compared to ezetimibe [adj.ROR = 1.99 (1.35–2.94)], and less often compared to statins [adj.ROR = 0.26 (0.25–0.28)]. Notably, hyperglycaemic AEs were reported more frequently by diabetic than by non-diabetic patients (P < 0.001), mostly occurred within 6 months of treatment and were reversible upon drug discontinuation. Conclusion In a real-world setting, PCSK9i treatment was associated with increased reporting of mild hyperglycaemia, but not diabetes. While initial monitoring is warranted, the favourable glycaemic safety profile compared to statins supports their essential role in the management of lipid disorders.

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.

Background Current guidelines recommend an early invasive strategy for patients with non-ST segment elevation myocardial infarction (NSTEMI). Purpose To evaluate whether early invasive strategy is associated with better outcome among patients with chronic kidney disease (CKD). Methods Retrospective cohort analysis of consecutive patients with NSTEMI between 2008 and 2021. Glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation. Invasively treated patients were dichotomized into early ( Results Final study population comprised 7,107 NSTEMI patients, of whom 3,172 (45%) had eGFR Conclusion Among invasively treated NSTEMI patients, the benefit of early invasive strategy is modified by CKD, and limited to those with eGFR ≥45 ml/min/1.73m2. Funding Acknowledgement Type of funding sources: None.

Background Cardiac electroporation is a promising novel non-thermal ablation method, gaining significant interest with recent first-in-man data suggesting effective cardiac lesion generation with no collateral damage. Nevertheless, significant knowledge gaps exist regarding its electrophysiological consequences in cardiomyocytes, including; cell specificity, protocol optimization, irreversibility threshold, recovery time-constants, and the mechanistic nature of its cytolytic and anti-arrhythmic properties. Purpose Establishing an innovative in-vitro model for the study of cardiac electroporation-ablation, utilizing human induced pluripotent stem cells (hiPSCs). Methods and results Healthy-control hiPSC-derived cardiomyocytes were enzymatically dissociated and seeded as circular cell sheets (hiPSC-CCSs). Electroporation-ablation experiments were performed using a custom designed high-frequency electroporation (HF-EP) generator. Two needle-shaped electrodes were used for HF-EP delivery (Figure 1). Subsequently, detailed voltage- and Ca2+-mapping studies of the hiPSC-CCSs were conducted (Figure 2). HF-EP application resulted in the generation of electrically isolated lesions within the hiPSC-CCSs (Figure 3). Further characterization of the temporal changes and electrophysiological properties following electroporation revealed that; (1) lesions persisted over prolonged periods of time (days), indicating irreversible electroporation, (2) a temporal decrease in lesion dimensions was noted, consistent with a significant reversible electroporation component (Figures 3–5), (3) most tissue recovery had occurred within the first 15 minutes following electroporation, with little recovery beyond that time-frame, (4) increasing pulse-number augmented lesion area as well as the proportion of irreversible damage, and (5) electroporation sensitization was achieved by increasing extracellular Ca2+, indicating its crucial role in electroporation cytolysis, potentially via direct cellular toxicity and apoptosis facilitation (Figures 5–6). Finally, evaluating for HF-EP anti-arrhythmic properties, we targeted multiple rotors or focal triggered-activity generated in the hiPSC-CCSs. HF-EP application generated sustained line-blocks, isolating arrhythmogenic substrates within the hiPSC-CCSs while blocking the propagation of arrhythmic wavefronts (Figure 7). Conclusion Our results demonstrate the ability to study cardiac electroporation utilizing hiPSC-derived cardiomyocytes, provide novel insights into its temporal and electrophysiological characteristics, facilitate electroporation protocol optimization, screen for potential electroporation sensitizers, and to study its mechanistic nature and anti-arrhythmic properties. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Division of Cardiology, and Tamman Cardiovascular Research Institute, Leviev Heart Center, Sheba Medical Center - Tel Hashomer, Ramat-Gan, Israel Figures 1–4Figures 5–7

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

Introduction Contemporary guidelines recommend a universal cutoff of 14 for the ratio between early mitral flow wave and early diastolic mitral annulus velocity measured by tissue doppler (E/e' ratio). While age-dependent normal E/e' values have been suggested, outcome data is lacking. Purpose We sought to evaluate the modification effect of age and gender on the prognostic value of the E/e' ratio. Methods Consecutive patients who underwent echocardiographic evaluation between 2009 and 2021 (N=104,315) in a single tertiary cardiovascular center. Patients with left or right ventricular dysfunction, any significant valvular disease, structural heart disease or evidence of pulmonary hypertension were excluded. Cancer and mortality data were available for all subjects from national registries. Patients with a metastatic malignancy at baseline or during follow up were excluded. Cox regression models were applied. Results Overall, 44,541 patients were included in the final analysis. Mean age was 55±17, 59% were male and 63% of the exams were performed in an outpatient setting. An elevated E/e' ratio above 14 was documented in 2,598 (7%) patients. During a median follow-up of 5.7 (IQR 2.8–9.1) years, 5,015 (11.3%) patients died. Kaplan Meier survival analysis demonstrated that the cumulative probability of death at 6 years was 23.4% (21.6–25.3) among patients with elevated E/e' ratio compared with 9.7% (9.3–10.0) among patients with E/e'80, respectively. In a sensitivity analysis, similar findings were seen in when excluding patients with mild hypertrophy (maximal wall thickness >12mm) and without any mitral annulus calcification. Conclusion In apparently normal hearts, an elevated E/e' ratio is independently associated with increased mortality. This association is more pronounced among men and is attenuated with increased age. This study supports the need for gender-specific and age-specified outcome data with respect to measures of diastolic dysfunction. Funding Acknowledgement Type of funding sources: None. Survival by age and gender groupsE/e' >14 and mortality by age and gender

Background One of the major barriers to an improved mechanistic understanding of atrial fibrillation (AF), and thus in the pipeline of drug development, has been a lack of appropriate tissue models, especially in small animals. Aim We propose an advanced anatomical ex-vivo model based on rat atria for acute assessment of AF susceptibility. This novel model could yield a better understanding of arrhythmia mechanisms as well as the development of potential therapeutic strategies for the prevention or termination of atrial arrhythmias. Methods Wistar rats atria (N=25) were isolated, flattened and pinned to a custom-made silicon plate. Atria were superfused with an oxygenized Tyrode's solution. Tissues were then loaded with a voltage-sensitive dye and mapped using a high-resolution optical mapping system. AF was induced with 1uM carbamylcholine (N=23) coupled with pacing maneuvers and treated with 30uM Vernakalant (N=10) or 10uM Flecainide (N=10). Finally, the feasibility of a new ablation technique (electroporation) was evaluated. Results Optical mapping results suggested that the superfusion procedure led to a fast atrial recovery. Sinus activity was conserved for all atria for a long period. All the anatomical landmarks were clearly visualized. The acquired optical signals were analyzed during sinus rhythm and pacing, which allowed the creation of detailed activation maps and measurements of action potential duration (APD) and conduction velocity (CV) at different pacing rates. The resulting APD restitution curves revealed electrical excitation at high pacing rates (cycle length between 50ms and 300ms) with a relatively flattened curve. AF was successfully induced and optically mapping confirmed the presence of reentrant activity. AF was successfully treated using Vernacalant and Flecainide. Finally, we demonstrated the feasibility of a new ablation approach (electroporation) for creation of a continuous linear lesion serving as a functional block. Conclusion The isolated superfused atria model, coupled with voltage-sensitive dyes, can be utilized for long-term high-resolution functional imaging of the atria during sinus rhythm, pacing and arrhythmogenic activity. This allows the study of the atrial electrophysiological properties, the mechanisms involved in AF initiation, perpetuation, and termination as well as the study of drug and new ablation modalities. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council (ERC) Spontaneous activation of isolated atria

Introduction While Cardiovascular disease (CVD) and cancer share common risk factors, data on the temporal association between the occurrence of CVD and cancer is limited. Purpose This study investigated the association between incident CVD events future cancer among apparently healthy subjects. Methods We evaluated asymptomatic self-referred adults who participated in a screening program. All subjects were free of CVD and cancer at baseline. CVD was defined as the composite of acute coronary syndrome, percutaneous coronary intervention, or stroke. Study endpoint was the development of cancer during follow up. Cancer and mortality data were available for all subjects from national registries. Cox regression models were applied with CVD as a time-dependent covariate and death as a competing risk event. Results Final study population included 26,574 subjects. Median age was 46 years (Interquartile range [IQR] 40–53) and 69% were men. During median follow up time of 10 years (IQR 3–16) 2,463 (9%) subjects developed CVD, 2,040 (8%) developed cancer and 869 (3%) died. Most common cancer types were prostate among men (N=406, 2.2%) and breast among women (N=283, 3.4%). Compared with patients who were free of CVD and cancer during follow up, risk of death was 5, 34 and 54 times higher for patients who developed CVD event, cancer, or both during follow up, respectively (p Conclusion Incident CVD is independently associated with increased risk of subsequent cancer diagnosis among young adults. Active cancer surveillance should be considered among young patients recovering from a CVD event. Funding Acknowledgement Type of funding sources: None.

Objectives This study aimed to compare permanent pacemaker implantation (PPMI) rates among patients undergoing Trans-catheter Aortic Valve Implantation (TAVI) with first generation (G1) versus second generation (G2) valves and the impact of PPMI on long-term mortality. Background PPMI is a known adverse event after TAVI. Recently, two novel iterations of valve designs of both the balloon expandable valves (BEV) and self-expanding valves (SEV) were introduced as a second generation valves. Methods All patients included in the Israeli multicenter TAVI registry were grouped according to valve type (BEV vs. SEV) and generation (G1 vs. G2). A comparison was made for clinical and outcome indices of patients undergoing TAVI with G1 and G2 in each of the valve systems. Results A total of 1377 patients were included. The incidence of PPMI did not differ between G1-BEV versus G2-BEV (15.3% vs. 17.4%; p = 0.598) nor between G1-SEV versus G2-SEV (23.4% vs. 20.3%; p = 0.302). Depth of implantation and complete right bundle branch block were independently associated with PPMI post-TAVI in both valve systems. PPMI was not associated with an increased risk for 2-year mortality. Conclusions The incidence of PPMI remains a relevant adverse event post-TAVI even when the newer generation valves are used. Since the predictors for PPMI are well established, a standardized approach for the management of conduction disorders is much needed.

To evaluate the association of invasive management (coronary angiogram) with all-cause mortality among older adult (≥80 years of age) patients presenting with non-ST elevation myocardial infarction (NSTEMI) by frailty status.This study used a retrospective cohort of consecutive older adult patients who were hospitalized with NSTEMI as their primary clinical diagnosis between August 1, 2008, and December 31, 2019. Cox regression models were applied with stratification by frailty status (low, medium, and high). Extensive sensitivity analyses were conducted including propensity score matching and inverse probability treatment weighting models.The study population included 2317 patients with median age of 86 years (IQR, 83-90 years) of whom 1243 (53.6%) were men. Patients who were managed invasively (n=581 [25%]) were less likely to be frail (7% vs 44%, P.001). During the follow-up (median, 19 months, IQR, 4-41 months), 1599 (69%) patients died. In a multivariable Cox model, invasive approach was associated with adjusted hazard ratio (HR) of 0.61 (95% CI, 0.53 to 0.71) for the risk of death. The benefit of invasive approach was consistent among low, medium, and high frailty subgroups with adjusted HRs of 0.74 (95% CI, 0.58 to 0.93), 0.65 (95% CI, 0.50 to 0.85), and 0.52 (95% CI, 0.34 to 0.78), respectively (P for interaction = 0.48). Results were consistent with propensity score matching and inverse probability treatment weighting analyses (HR, 0.6; 95% CI, 0.50 to 0.71 and HR, 0.67; 95% CI, 0.55 to 0.82, respectively). Sensitivity analysis addressing potential immortal time bias and residual confounding yielded similar results.Invasive approach is associated with improved survival among older adults with NSTEMI irrespective of frailty status.

Data on the independent association of moderate aortic stenosis (AS) with excess mortality, even when it does not progress to severe AS, are limited. The aims of this study were to evaluate the association of moderate AS with poor survival and to identify clinically important modifiers of that association.Consecutive patients who underwent echocardiographic evaluation between 2007 and 2019 were included. All-cause mortality and cancer data were available for all patients from national registries. Cox regression survival models were applied, with censoring of patients who developed metastatic cancer, developed more than moderate AS, or underwent aortic valve intervention during follow-up.The study population included 92,622 patients. There were 2,202 patients (2%) with moderate AS, with a median age of 79 years (interquartile range, 70-85 years), of whom 1,254 (57%) were men. During median follow-up of 5 years (interquartile range, 3-8 years), 19,712 patients (21%) died. The cumulative probability of death at 5 years was higher for patients with moderate AS (46% vs 18%, respectively, log-rank P .001). Propensity score matching analysis (n = 2,896) that included clinical, laboratory, and echocardiographic predictors of poor survival demonstrated that compared with patients with mild or less AS, those with moderate AS were 17% more likely to die (95% CI, 1.04-1.30; P = .007). Moreover, the model showed that the moderate AS-associated risk was ejection fraction and age dependent, with a more pronounced association among nonoctogenarian patients (P for interaction = .001) and those with reduced ejection fractions (P for interaction = .016).Moderate AS is independently associated with excess mortality, even when it does not progress to severe AS. The associated risk is more pronounced among patients with reduced ejection fractions and those80 years of age.

Clinical and experimental data support a critical role for inflammation in cardiovascular disease. The purpose of the current study was to examine the relation between an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR), and incident atrial fibrillation (AF) in asymptomatic adults. We investigated 21,118 self-referred men and women who were annually screened in a tertiary medical center. All subjects were free of AF at baseline and had their serum NLR calculated at the first annual visit. Subjects were divided into 2 groups based on their baseline NLR: Low (2.83; n = 17,524) and high (≥2.83; n = 3,594; Upper Sextile). The primary endpoint was new onset AF during follow-up. Mean age of study population was 48 ± 10 years and 72% were men. A total of 563 (2.7%) incident events occurred during an average follow-up of 7.5 ± 5 years. Unadjusted Cox regression analysis demonstrated that each 1 unit increase in NLR was associated with a significant 14% increase in risk of occurrence of a first AF event (95% confidence interval 1.06 to 1.23, p0.001) and 20% increased risk of death. Kaplan-Meier's survival analysis showed that the cumulative probability of incident AF was significantly higher among subjects with high NLR compared with low NLR group (p = 0.006). Interaction analysis with adjustment to clinical parameters showed that NLR-related risk was age-dependent, such that in the younger age-group (=50 years) high NLR group had two folds increased risk for AF event compared with low NLR group (95% confidence interval 1.08 to 3.51; p = 0.027) whereas among older subjects the rate of events was similar between both NLR groups (p = NS; p for interaction = 0.024). In conclusion, our findings suggest that high NLR is associated with increased risk of new onset AF. This finding is more pronounced among young adults.

Referral of low surgical risk (LSR) patients for transcatheter aortic valve implantation (TAVI) becomes common in multiple tertiary centers, and clinical trial data for this population are not available to date. We performed a retrospective analysis on an Israeli multicenter registry. LSR and intermediate-high surgical risk (I-HSR) were defined by a Society of Thoracic Surgery score of4% and ≥4%, respectively. The cohort included 2336 patients (LSR n = 1198, I-HLR n = 1138). As compared with LSR, patients with I-HSR were older and had significantly higher rates of baseline comorbidities. Although devices success rates (94% vs 96%), paravalvular leak (3.5% vs 5.2%), and permanent pacemaker implantation (17.2 vs 18%) were comparable (p0.05 for all comparisons), the safety outcome at 1 month (12.7% vs 9.8%), procedural mortality (1.9% vs 0.6%), and mortality at 3 years (30.1% vs 16.1%) were higher in patients with I-HSR (p0.05 for all comparisons). In a subanalysis of patients with very LSR, comparable rates of device success and safety outcomes were observed, whereas mortality at 1 to 3 years was lower. In conclusion, although procedural outcomes were comparable between LSR and I-HSR TAVI patients, the rates of short- and long-term mortality, as well as the safety outcome, were lower in LSR patients.