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Background Sex‐specific risk management may improve outcomes in congenital long QT syndrome (LQTS). We recently developed a prediction score for cardiac events (CEs) and life‐threatening events (LTEs) in postadolescent women with LQTS. In the present study, we aimed to develop personalized risk estimates for the burden of CEs and LTEs in male adolescents with potassium channel‐mediated LQTS. Methods and Results The prognostic model was derived from the LQTS Registry headquartered in Rochester, NY, comprising 611 LQT1 or LQT2 male adolescents from age 10 through 20 years, using the following variables: genotype/mutation location, QTc‐specific thresholds, history of syncope, and β‐blocker therapy. Anderson‐Gill modeling was performed for the end point of CE burden (total number of syncope, aborted cardiac arrest, and appropriate defibrillator shocks). The applicability of the CE prediction model was tested for the end point of the first LTE (excluding syncope and adding sudden cardiac death) using Cox modeling. A total of 270 CEs occurred during follow‐up. The genotype–phenotype risk prediction model identified low‐, intermediate‐, and high‐risk groups, comprising 74%, 14%, and 12% of the study population, respectively. Compared with the low‐risk group, high‐risk male subjects experienced a pronounced 5.2‐fold increased risk of recurrent CEs (P

Abstract Background Congenital Long QT Syndrome (LQTS) is a hereditary arrhythmic disorder. We aimed to assess the performance of current genetic variant annotation scores among LQTS patients and their predictive impact. Methods We evaluated 2025 patients with unique mutations for LQT1–LQT3. A patient‐specific score was calculated for each of four established genetic variant annotation algorithms: CADD, SIFT, REVEL, and PolyPhen‐2. The scores were tested for the identification of LQTS and their predictive performance for cardiac events (CE) and life‐threatening events (LTE) and then compared with the predictive performance of LQTS categorization based on mutation location/function. Score performance was tested using Harrell's C‐index. Results A total of 917 subjects were classified as LQT1, 838 as LQT2, and 270 as LQT3. The identification of a pathogenic variant occurred in 99% with CADD, 92% with SIFT, 100% with REVEL, and 86% with PolyPhen‐2. However, none of the genetic scores correlated with the risk of CE (Harrell's C‐index: CADD = 0.50, SIFT = 0.51, REVEL = 0.50, and PolyPhen‐2 = 0.52) or LTE (Harrell's C‐index: CADD = 0.50, SIFT = 0.53, REVEL = 0.54, and PolyPhen‐2 = 0.52). In contrast, high‐risk mutation categorization based on location/function was a powerful independent predictor of CE (HR = 1.88; p

IntroductionThe implantable cardioverter defibrillator (ICD) is effective for the prevention of sudden cardiac death (SCD) in patients with heart failure and a reduced ejection fraction (HFrEF). The benefit of the ICD in patients with advanced CKD, remains elusive. Moreover, the benefit of the ICD in patients with advanced chronic kidney disease (CKD) and HFrEF who are cardiac resynchronization therapy (CRT) recipients may be attenuated.HypothesisWe hypothesized that patients with CKD who are CRT recipients may derive less benefit from the ICD due to the competing risk of dying prior to experiencing an arrhythmia.MethodsThe study population included 1,015 patients receiving CRT with defibrillator (CRT-D) device for primary prevention of SCD who were enrolled in either (Multicenter Automated Defibrillator Implantation Trial) MADIT-CRT trial or the Ranolazine in High-Risk Patients with Implanted Cardioverter Defibrillator (RAID) trial. The cohort was divided into two groups based on the stage of CKD: those with Stage 1 to 3a KD, labeled as (S1-S3a)KD. The second group included patients with Stage 3b to stage 5 kidney disease, labeled as (S3b-S5)KD. The primary endpoint was any ventricular tachycardia (VT) or ventricular fibrillation (VF) (Any VT/VF).ResultsThe cumulative incidence of Any VT/VF was 23.5% in patients with (S1-S3a)KD and 12.6% in those with (S3b-S5)KD (p

Abstract Background Patients with heart failure (HF) represent a large population of patients who are at high risk for complications related to undiagnosed atrial fibrillation (AF). However, currently there are limited modalities available for early AF detection in this high‐risk population. An implantable cardiac monitor (ICM) is inserted subcutaneously and can provide long‐term arrhythmia information via remote monitoring. Methods and Results Confirm‐AF is a prospective randomized, nonblinded, two arm, multicenter clinical trial to be performed in the United States, enrolling 477 patients with a history of HF hospitalization and left ventricular ejection fraction >35% from 30 medical sites. Patients will be randomized in a 2:1 fashion to undergo ICM implant with remote monitoring and symptom‐triggered mobile app transmissions versus (vs.) Non‐ICM management and follow‐up. The primary objective of this trial is to compare the time to first detection of AF lasting > 5 min using an Abbott ICM compared to non‐ICM monitoring in symptomatic HF patients. This article describes the design and analytic plan for the Confirm‐AF trial. Conclusions The Confirm‐AF trial seeks to accurately define the burden of AF in high‐risk HF patients with LVEF > 35% using an Abbott ICM. A finding showing significantly higher incidence of AF along with improved clinical outcomes with ICM monitoring is expected to have substantial clinical implications and may change the method of monitoring high‐risk HF patients.

BackgroundCardioversion (CV) for atrial fibrillation (AF) is common. We aimed to assess changes in QTc over time following electrical CV (ECV) for persistent AF, and to compare the benefit of using continuous Holter monitoring vs. conventional follow-up by ECG.MethodsProspective observational cohort study. We comprised 90 patients admitted to our center for elective ECV due to persistent AF who were prospectively enrolled from July 2017 to August 2018. All patients underwent 7-days Holter started prior to ECV. Baseline QTc was defined as median QTc during 1 h post ECV. The primary endpoint was QTc prolongation defined as QTc ≥500 ms, or ≥10% increase (if baseline QTc was >480 ms). Conventional monitoring was defined as 2-h ECG post ECV.ResultsMean age was 67 ± 11 years and 61% were male. Median baseline QTc was 452 ms (IQ range: 431–479 ms) as compared with a maximal median QTc of 474 ms (IQ range: 433–527 ms; p

Background: Implantable cardioverter-defibrillator (ICD) programming to novel settings can reduce the risk of inappropriate therapies. Objective: The purpose of this study was to evaluate the impact of novel ICD programming after the first occurrence of ventricular tachycardia (VT). Methods: In MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy) patients who experienced a first occurrence of VT, the risk of subsequent inappropriate and appropriate ICD therapies and adverse cardiovascular events by ICD programming to Arm A (conventional: VT ≥170 bpm), Arm B (high rate: VT ≥200 bpm), or Arm C (duration delay: ≥60-second delay before therapy ≥170 bpm) was determined. Results: Among 205 patients, ICD programming changes were made in 30 patients (15%) after they experienced a VT episode; 117 patients (57%) were programmed to Arm A settings and 88 patients (43%) to Arm B/C settings. At 15-month follow-up, the cumulative probability of inappropriate ICD therapy was significantly lower in Arm B/C compared to Arm A (9% vs 20%; log-rank P = .029 for overall difference). The rate of appropriate ICD therapy also was significantly lower in Arm B/C compared to Arm A (32% vs 64%; log-rank P = .001 for overall difference). Multivariate analysis showed that patients programmed to Arm B/C after the occurrence of VT had a 71% reduction (P = .02) in the risk of inappropriate ICD therapies and a 43% reduction (P = .02) in the risk of appropriate ICD therapies compared to Arm A. Conclusion: The benefit of high-rate cutoff or duration delay settings in patients with an ICD is maintained after the first occurrence of VT.

Cardiological disorders contribute to a significant portion of the global burden of disease. Cardiology can benefit from Big Data, which are generated and released by different sources and channels, like epidemiological surveys, national registries, electronic clinical records, claims-based databases (epidemiological Big Data), wet-lab, and next-generation sequencing (molecular Big Data), smartphones, smartwatches, and other mobile devices, sensors and wearable technologies, imaging techniques (computational Big Data), non-conventional data streams such as social networks, and web queries (digital Big Data), among others. Big Data is increasingly having a more and more relevant role, being highly ubiquitous and pervasive in contemporary society and paving the way for new, unprecedented perspectives in biomedicine, including cardiology. Big Data can be a real paradigm shift that revolutionizes cardiological practice and clinical research. However, some methodological issues should be properly addressed (like recording and association biases) and some ethical issues should be considered (such as privacy). Therefore, further research in the field is warranted.

Introduction The objective of this study is to examine the temporal trends and patterns of regional and socioeconomic disparities in cardiovascular disease (CVD) in Canada during 2005–2016.Methods A total of 670 000 adults aged ≥20 years who participated in the Canadian Community Health Surveys between 2005 and 2016 were enrolled for this study. CVD referred to heart disease and stroke in this study. Equivalised household income was used as a proxy of socioeconomic status. Absolute and relative socioeconomic inequalities were measured by slope index of inequality (SII) and relative index of inequality (RII), respectively.Results In 2015/2016, the overall age-adjusted and sex-adjusted prevalence of heart disease and stroke was 4.80% (95% CI 4.61% to 4.98%) and 1.25% (95% CI 1.13% to 1.36%), respectively. Trend analyses suggested a significant decline in the age-adjusted and sex-adjusted prevalence of heart disease (P for trend

Abstract Introduction Cardiac resynchronization therapy (CRT) may be pro‐arrhythmic in patients with non‐left bundle branch block (non‐LBBB). We hypothesized that combined assessment of risk factors (RF) for ventricular tachyarrhythmias (VTAs) can be used to stratify non‐LBBB patients for CRT implantation. Methods The study comprised 412 non‐LBBB patients from MADIT‐CRT randomized to CRT‐D (n = 215) versus ICD only (n = 197). Best‐subset regression analysis was performed to identify RF associated with increased VTA risk in CRT‐D patients without LBBB. The primary end point was first occurrence of sustained VTA during follow‐up. Secondary end points included VTA/death and appropriate shock. Results Four RFs were associated with increased VTA risk: blood urea nitrogen >25mg/dl, ejection fraction

Background: Long-term morbidity and mortality data among ischemic heart disease (IHD) patients of different ethnicities are conflicting. We sought to determine the independent association of ethnicity and all-cause mortality over two decades of follow-up of Israeli patients.Methods: Our study comprised 15,524 patients including 958 (6%) Arab patients who had been previously enrolled in the Bezafibrate Infarction Prevention (BIP) registry between February 1, 1990, and October 31, 1992, and subsequently followed-up for long-term mortality. We compared clinical characteristics and outcomes of Israeli Arabs and Jews. Propensity score matching (PSM) (1:2 ratios) was used for validation.Results: Arab patients were significantly younger (56 ± 7 years vs. 60 ± 7 years; p < 0.001; respectively), and had more cardiovascular disease (CVD) risk factors. Kaplan-Meier survival analysis showed that all-cause mortality was significantly higher among Arab patients (67 vs. 61%; log-rank p < 0.001). Multivariate adjusted analysis showed that mortality risk was 49% greater (HR 1.49; 95% CI: 1.37–1.62; p < 0.001) among Arabs.Conclusions: Arab ethnicity is independently associated with an increased 20-year all-cause mortality among patients with established IHD.

Objective: To estimate the burden of myocarditis (MC), alcoholic cardiomyopathy (AC), and other cardiomyopathy (OC) for 195 countries and territories from 1990 to 2017.Methods: We collected detailed information on MC, AC, and OC between 1990 and 2017 from the Global Burden of Disease study 2017, which was designed to provide a systematic assessment of health loss due to diseases and injuries in 21 regions, covering 195 countries and territories. Estimates of MC, AC, and OC burden were produced using a standard Cause of Death Ensemble model and a Bayesian mixed-effects meta-regression tool, and included prevalence, deaths, years lived with disability (YLDs), and years of life lost (YLLs). All estimates were presented as counts, age-standardized rates per 100,000 people and percentage change, with 95% uncertainty intervals (UIs).Results: Worldwide, there were 1.80 million (95% UI 1.64–1.98) cases of MC, 1.62 million (95% UI 1.37–1.90) cases of AC and 4.21 million (95% UI 3.63–4.87) cases of OC, contributing to 46,486 (95% UI 39,709–51,824), 88,890 (95% UI 80,935–96,290), and 233,159 (95% UI 213,677–248,289) deaths in 2017, respectively. Furthermore, globally, there were 131,376 (95% UI 90,113–183,001) YLDs and 1.26 million (95% UI 1.10–1.42) YLLs attributable to MC, 139,087 (95% UI 95,134–196,130) YLDs and 2.84 million (95% UI 2.60–3.07) YLLs attributable to AC, and 353,325 (95% UI 237,907–493,908) YLDs and 5.51 million (95% UI 4.95–5.99) YLLs attributable to OC in 2017. At the national level, the age-standardized prevalence rates varied by 10.4 times for MC, 252.6 times for AC and 38.1 times for OC; the age-standardized death rates varied by 43.9 times for MC, 531.0 times for AC and 43.3 times for OC; the age-standardized YLD rates varied by 12.4 times for MC, 223.7 times for AC, and 34.1 times for OC; and the age-standardized YLL rates varied by 38.4 times for MC, 684.8 times for AC, and 36.2 times for OC. Between 1990 and 2017, despite the decreases in age-standardized rates, the global numbers of prevalent cases, deaths, YLDs, and YLLs have increased for all the diseases.Conclusion: Accurate assessment of the burden of MC, AC, and OC is essential for formulating effective preventative prevention and treatment programs and optimizing health system resource allocation. Our results suggest that MC, AC, and OC remain important global public health problems with increasing numbers of prevalent cases, deaths, YLDs, and YLLs over the past decades, and there are significant geographic variations in the burden of these diseases. Further research is warranted to expand our knowledge of potential risk factors and to improve the prevention, early detection and treatment of these diseases.

Background Sex differences in outcome have been reported in patients with congenital long QT syndrome. We aimed to report on the incidence of time‐dependent life‐threatening events in male and female patients with long QT syndrome with an implantable cardioverter defibrillator (ICD). Methods and Results A total of 60 patients with long QT syndrome received an ICD for primary or secondary prevention indications. Life‐threatening events were evaluated from the date of ICD implant and included ICD shocks for ventricular tachycardia, ventricular fibrillation, or death. ICDs were implanted in 219 women (mean age 38±13 years), 46 girls (12±5 years), 55 men (43±17 years), and 40 boys (11±4 years). Mean follow‐up post‐ICD implantation was 14±6 years for females and 12±6 years for males. At 15 years of follow‐up, the cumulative probability of life‐threatening events was 27% in females and 34% in males (log‐rank P=0.26 for the overall difference). In the multivariable Cox model, sex was not associated with significant differences in risk first appropriate ICD shock (hazard ratio, 0.83 female versus male; 95% CI, 0.52–1.34; P=0.47). Results were similar when stratified by age and by genotype: long QT syndrome type 1 (LQT1), long QT syndrome type 2 (LQT2), and long QT syndrome type 3 (LQT3). Incidence of inappropriate ICD shocks was higher in males versus females (4.2 versus 2.7 episodes per 100 patient‐years; P=0.018), predominantly attributed to atrial fibrillation. The first shock did not terminate ventricular tachycardia/ventricular fibrillation in 48% of females and 62% of males (P=0.25). Conclusions In patients with long QT syndrome with an ICD, the risk and rate of life‐threatening events did not significantly differ between males and females regardless of ICD indications or genotype. In a substantial proportion of patients with long QT syndrome, first shock did not terminate ventricular tachycardia/ventricular fibrillation.

Background Following cryptogenic stroke, guidelines recommend cardiac monitoring for occult atrial fibrillation (AF). We aimed to evaluate predictors of AF during long‐term implantable cardiac monitoring. Methods and Results We studied 293 consecutive patients who underwent implantable cardiac monitor implant (Medtronic LINQ) following hospitalization for cryptogenic stroke at the University of Rochester Medical Center from January 2013 to September 2018. Multivariable Cox proportional hazards regression modeling was used to identify predictors of AF during long‐term monitoring. At 36 months of follow‐up, the cumulative rate of implantable cardiac monitor–detected AF events was 32% in the total study population. Multivariable analysis identified age ≥70 years as the most powerful predictor of the development of AF events during follow‐up (hazard ratio, 2.28 [95% CI, 1.39–3.76]; P=0.001). Replacing age with the CHA2DS2‐VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex category) score resulted in a weaker association, for which each 1‐point increment in the CHA2DS2‐VASC score was associated with an 18% increased risk of developing AF (95% CI, 1.00–1.38; P=0.047). Consistent results were shown using Kaplan–Meier analysis by age and by the CHA2DS2VASc score. Conclusions Cryptogenic stroke patients continue to develop AF episodes during 36 months of implantable cardiac monitoring following the index event. Age is the most powerful predictor of occult AF in this population.

Abstract Background Ethnicity may affect graft longevity and recipient mortality after heart transplantation (HTx). We hypothesized that differences in ethnic origin between Arabs and Jews undergoing HTx in Israel may contribute to differences in long-term outcomes. Methods The study population comprised all 254 patients who underwent HTx between 1991 and 2017 in a tertiary medical center located in the center of Israel. Patients were categorized as either Jews (226 patients, 89%) or Arabs (28 patients, 11%). The primary end point was cardiac allograft vasculopathy (CAV), secondary end points were cardiovascular (CV) mortality and the combined end point of CAV/CV mortality. Results In comparison with Jews, Arab patients were significantly younger (ave. age 42 vs. 50) and had shorter in-hospital stay (45 vs. 80 days). However, Kaplan-Meier survival analysis showed that at 10 years of follow-up CAV rates were significantly higher among Arabs (58%) compared with Jews (23%; log-rank P = 0.01) for the overall difference during follow-up. Similar results were shown for the separate end point of CV mortality and the combined end point of CAV/CV mortality. Multivariate analysis, which controlled for age, gender, statin treatment, and other potential confounders, showed that Arab recipient ethnic origin was associated with a significant > 2.5-fold (p = 0.01) increase in the risk for CAV; a > 4-fold increase in the risk for CV mortality (p = 0.001); and approximately 4-fold increase in the risk for the combined end point (p = 0.001). These findings were validated by propensity score analysis. Conclusions Our data suggest that Arab ethnic origin is associated with a significantly increased risk for CAV and mortality following HTx. Suggested explanations contributing to ethnic disparities in Israel include socioeconomic, environmental and genetic factors. Further studies are required to evaluate whether more aggressive risk factor management in the Israeli Arab population following HTx would reduce CAV and CV mortality in this high-risk population. Increased awareness and early intervention of the Israeli healthcare system and cooperation with the Arab community is of paramount importance.

Background: Infections of cardiac implantable devices (CIEDI) have poor outcomes despite improvement in lead extraction (TLE) procedures. Methods: To explore the influence of CIEDI on the outcomes of TLE and the differences between patients with systemic (Sy) vs. local (Lo) CIEDI, we performed a sub-analysis of the EORP ELECTRa (European Lead Extraction ConTRolled) Registry. Results: Among 3555 patients enrolled by 73 centers in 19 Countries, the indication for TLE was CIEDI in 1850: 1170 with Lo-CIEDI and 680 with Sy-CIEDI. Patients with CIEDI had a worse in-hospital prognosis in terms of major complications (3.57% vs. 1.71%; p = 0.0007) and mortality (2.27% vs. 0.49%; p < 0.0001). Sy-CIEDI was an independent predictor of in-hospital death (H.R. 2.14; 95%CI 1.06–4.33. p = 0.0345). Patients with Sy-CIEDI more frequently had an initial CIED implant and a higher prevalence of comorbidities, while subjects with Lo-CIEDI had a higher prevalence of previous CIED procedures. Time from signs of CIEDI and TLE was longer for Lo-CIEDI despite a shorter pre-TLE antibiotic treatment. Conclusions: Patients with CIEDI have a worse in-hospital prognosis after TLE, especially for patients with Sy-CIEDI. These results raise the suspicion that in a relevant group of patients CIEDI can be systemic from the beginning without progression from Lo-CIEDI. Future research is needed to characterize this subgroup of patients.

Abstract Background Patients with type 2 diabetes present with an accelerated atherosclerotic process. Animal evidence indicates that dipeptidyl peptidase-4 inhibitors (gliptins) have anti-inflammatory and anti-atherosclerotic effects, yet clinical data are scarcely available. Design and methods A prospective, randomized, open-label study was performed in 60 patients with coronary artery disease (CAD) and type 2 diabetes, who participated in a cardiac rehabilitation program. After a washout period of 3 weeks, patients were randomized in a 2:1 ratio to receive combined vildagliptin/metformin therapy (intervention group: n = 40) vs. metformin alone (control group: n = 20) for a total of 12 weeks. Blinded assessment of interleukin-1ß (IL-1ß, the primary endpoint), hemoglobin A1c (HbA1c), and high sensitivity C reactive protein (hsCRP), were performed at baseline and after 12 weeks. Results Mean age of study patients was 67 ± 9 years, 75% were males, and baseline HbA1c and inflammatory markers levels were similar between the two groups. At 12 weeks of follow up, levels of IL-1ß, hsCRP, and HbA1c were significantly lower in the intervention group as compared with the control group. There was a continuous elevation of IL-1ß among the control group, which was not observed in the intervention group (49 vs. 4%, respectively; p

IntroductionCardiac implantable electronic device (CIED) trans venous lead extraction (TLE) is technically challenging. Whether the use of a laser sheath reduces complications and improves outcomes is still in debate. We therefore aimed at comparing our experience with and without laser in a large referral center.MethodsInformation of all patients undergoing TLE was collected prospectively. We retrospectively compared procedural outcomes prior to the introduction of the laser sheath lead extraction technique to use of laser sheath.ResultsDuring the years 2007-2017, there were 850 attempted lead removals in 407 pts. Of them, 339 (83%) were extracted due to infection, device upgrade/lead malfunction in 42 (10%) cases, and other (7%). Complete removal (radiological success) of all leads was achieved in (88%). Partial removal was achieved in another 6% of the patients. Comparison of cases prior to and after laser technique introduction, showed that with laser, a significantly smaller proportion of cases required conversion to femoral approach [31/275 (6%) laser vs. 40/132 (15%) non-laser; pConclusionIntroduction of laser lead removal resulted in decreased need to convert to femoral approach, albeit without improving success rates or preventing major complications.

BackgroundWe wanted to explore the association of metabolic syndrome (MetS) versus its individual components with 20‐year all‐cause mortality among patients with stable coronary artery disease. Methods and ResultsThe cohort comprised 12 403 nondiabetic patients with stable coronary artery disease who were enrolled in the Bezafibrate Infarction Prevention Registry between February 1990 and October 1992 and followed up through December 2014. The study cohort was divided into 4 groups: patients without MetS or impaired fasting glucose (IFG), patients with IFG but without MetS, patients with MetS but without IFG, and patients with both MetS and IFG. Kaplan‐Meier survival analysis showed that at 20 years of follow‐up, the rates of all‐cause mortality were the highest among patients with both MetS and IFG (66%). Patients with IFG without MetS experienced a significantly higher mortality rate compared with those with MetS without IFG (61% versus 56%; log‐rank P