Search

Background: There are limited data on clinical and arrhythmic outcomes after a first ventricular tachyarrhythmia (VTA) in heart failure (HF) patients who receive a primary prevention implantable cardioverter-defibrillator (ICD)., Objective: This study was designed to quantify the burden of and to identify risk factors for recurrent VTA in this population and to evaluate the risk of all-cause mortality associated with recurrent VTA., Methods: The study comprised 789 patients who experienced VTA following primary prevention ICD implantation in 5 ICD trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, RAID). Landmark analysis was used to quantify the burden and to identify predictors of recurrent VTA. Time-dependent analysis was used to evaluate the association of VTA recurrence with subsequent mortality., Results: The mean age of the study patients was 63 years, and 17% were women. The cumulative probability of experiencing at least 1 recurrent VTA episode at 3 years after a first VTA episode was 60%; the recurrent VTA burden after a first event during 3 years was 2.8 episodes per patient. The risk of recurrent VTA remained ≥56% at 3 years regardless of baseline clinical and echocardiographic risk factors. VTA recurrence was associated with a significant 2-fold increased risk of subsequent all-cause mortality., Conclusion: Patients with a primary prevention ICD who experience an episode of VTA are at high risk of recurrent VTA, regardless of baseline risk factors. Recurrent VTA is associated with a pronounced increase in the risk of death. These findings suggest a need for early intervention after a first VTA in patients who receive a primary prevention ICD., Competing Interests: Disclosures Ilan Goldenberg: research grants from Boston Scientific, Zoll, Medtronic, Biosense Webster, and Biotronik; David T. Huang: research grants from Medtronic, Biosense Webster, and Biotronik; Valentina Kutyifa: research grants from Boston Scientific; Wojciech Zareba: research grants from Boston Scientific; Mehmet K. Aktaş: research grants from Abbott, Boston Scientific, and Medtronic., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Women with congenital long QT syndrome (LQTS) experience increased cardiac event risk after the onset of adolescence, perhaps stemming from the known modulating effects of sex hormones on the cardiac potassium channels., Objective: We hypothesized that the effect of sex hormones on cardiac ion channel function may modify electrocardiographic (ECG) parameters associated with the propensity for ventricular tachyarrhythmias during the menstrual cycle in women with LQTS., Methods: We prospectively enrolled 65 women with congenital LQTS (type 1 LQTS [LQT1], n = 24 [36.9%]; type 2 LQTS [LQT2], n = 20 [30.8%]) and unaffected female relatives (n = 21 [32.3%]). Patients underwent three 7-day ECG recordings during their menstrual cycles. Simultaneous saliva testing of sex hormone levels was conducted on the first day of each 7-day ECG recording cycle., Results: The mean age was 35 ± 8 years, without a significant difference among the groups. In women with LQT2, linear mixed effects models showed significant inverse correlations of the corrected QT interval with progesterone levels (P < .001) and with the progesterone to estradiol ratio (P < .001). Inverse relationships of the R-R interval with estradiol levels (P = .003) and of the T-wave duration with testosterone levels (P = .014) were also observed in women with LQT2. In contrast, no significant associations were observed between ECG parameters and sex hormone levels in women with LQT1 or unaffected relatives., Conclusion: This is the first study to prospectively assess correlations between repolarization dynamics and sex hormone levels during the menstrual cycle in women with congenital LQTS. Our findings show genotype-specific unique corrected QT dynamics during the menstrual cycle that may affect the propensity for ventricular tachyarrhythmia in women with LQTS, particularly women with LQT2., (Copyright © 2022. Published by Elsevier Inc.)

Background: The new high-sensitivity cardiac troponin T (hs-cTnT) is now widely used in the United States., Objectives: We aimed to examine outcomes associated with the introduction of the new 5 th generation hs-cTnT assay among patients presenting to the emergency department (ED) with cardiovascular (CV) disorders., Methods: The study comprised 5377 patients presenting to the ED with CV disorders between January and September 2018. Outcomes included rates of direct ED discharge, cardiac testing/procedures, and mortality. CV indications for troponin testing were categorized as rule-out acute coronary syndrome (RO-ACS) and other-CV (O-CV)., Results: Mean age was 62 ± 17 years, and 47% were female. Demographics and medical history did not differ significantly between the troponin groups. The use of hs-cTnT was associated with increased rates of direct discharge from the ED in the RO-ACS (48% vs. 37%; p < 0.01), but not in the O-CV (25% vs. 25%) cohort. Cardiac tests/procedures were more often performed after hs-cTnT vs. cTnT testing in both cohorts (45% vs. 41% for RO-ACS, and 33% vs. 28% for O-CV; p < 0.05 for both). Multivariate analysis demonstrated that hs-cTnT was not associated with a significant increase in postdischarge mortality in both cohorts (RO-ACS: hazard ratio = 1.47 [p = 0.13], O-CV: hazard ratio = 0.97 [p = 0.87])., Conclusions: Among patients with RO-ACS, hs-cTnT implementation resulted in increased rates of direct home discharge from the ED, without a significant increase in postdischarge mortality. Among patients presenting with O-CV indication, hs-cTnT implementation resulted in increased rates of cardiac testing procedures without an effect of ED discharge rates or long-term mortality., (Copyright © 2022. Published by Elsevier Inc.)

Background: Clinical risk assessment with quantitative formal risk scores may add to intuitive physician risk assessment and are advised by the international guidelines for the management of acute coronary syndrome (ACS) patients. Most previous studies have used the binary regression/classification approach (dead/alive) for long-term mortality post-ACS, without considering the time-to-event as in survival analysis. The use of machine learning (ML)-based survival models has yet to be validated. The primary objective was to compare survival prediction performance of 1-year mortality following ACS of two newly developed ML-based models [random survival forest (RSF) and deep learning (DeepSurv)] with the traditional Cox-proportional hazard (CPH) model. The secondary objective was external validation of the findings., Methods: This was a retrospective, supervised learning data mining study based on the Acute Coronary Syndrome Israeli Survey (ACSIS) and the Myocardial Ischemia National Audit Project (MINAP). The ACSIS data were divided to train/test in a 70/30 fashion. Next, the models were externally validated on the MINAP data. Harrell's C-index, inverse probability of censoring weighting (IPCW), and the Brier-score were used for models' performance comparison., Results: RSF performed best among the three models, with Harrell's C-index on training and testing sets reaching 0.953 and 0.924 respectively, followed by CPH multivariate selected model (0.805/0.849), CPH Univariate selected model (0.828/0.806), DeepSurv model (0.801/0.804), and the traditional CPH model (0.826/0.738). The RSF model also had the highest performance on the validation data set with 0.811 for Harrell's C-index, 0.844 for IPCW, and 0.093 for Brier score. The CPH model performance on the validation set had C-index range between 0.689 to 0.790, 0.713 to 0.826 for IPCW, and 0.094 to 0.103 Brier score., Conclusions: RSF survival predictions for long-term mortality post-ACS show improved model performance compared with the classic statistical method. This may benefit patients by allowing better risk stratification and tailored therapy, however further prospective evaluations are required., Competing Interests: Conflict of interests The authors had no conflict of interests., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Use of oral contraceptives (OCs) may modulate the clinical course of women with congenital long QT syndrome (LQTS). The safety of OC use by sex hormone content has not been assessed in women with LQTS., Objective: We aimed to evaluate the association of OCs with the risk of cardiac events (CEs) in women with LQTS., Methods: Beginning in 2010, information on menarche onset, OC use, pregnancy, and menopause were obtained from women enrolled in the Rochester LQTS Registry. Type of OC was categorized as progestin-only, estrogen-only, or combined (estrogen/progestin). Andersen-Gill multivariate modeling was used to evaluate the association of time-dependent OC use with the burden of CE (total number of syncope, aborted cardiac arrest, and LQTS-related sudden cardiac death) from menarche onset through 40 years. Findings were adjusted for genotype, corrected QT duration, and time-dependent β-blocker therapy., Results: A total of 1659 women with LQTS followed through March 2021, of whom 370 (22%) were treated with an OC. During a cumulative follow-up of 35,797 years, there were a total of 2027 CE. Multivariate analysis showed that progestin-only OC was associated with a pronounced 2.8-fold (P = .01) increased risk of CEs in women who did not receive β-blocker therapy, while β-blockers were highly protective during progestin-only OC treatment (hazard ratio 0.22; P = .01; P = .006 for β-blocker-by-OC interaction). The risk associated with OC use without concomitant β-blocker treatment was pronounced in women with LQTS type 2., Conclusion: Our findings suggest that progestin-only OC should not be administered in women with LQTS without concomitant β-blocker therapy. OCs should be used with caution in women with LQTS type 2., (Copyright © 2021. Published by Elsevier Inc.)

Background: Various prognostic models for mortality prediction following ST-segment elevation myocardial infarction (STEMI) have been developed over the past two decades. Our group has previously demonstrated that machine learning (ML)-based models can outperform known risk scores for 30-day mortality post-STEMI. The study aimed to redevelop an ML-based random forest prediction model for 30-day mortality post-STEMI and externally validate it on a large cohort., Methods: This was a retrospective, supervised learning, data mining study developed on the Acute Coronary Syndrome Israeli Survey (ACSIS) registry and the Myocardial Ischemia National Audit Project (MINAP) for external validation. Patients included received reperfusion therapy for STEMI between 2006 and 2016. Discrimination and calibration performances were assessed for two developed models and compared with the Global Registry of Acute Cardiac Events (GRACE) score., Results: The ACSIS cohort (2,782 included /15,212 total) and MINAP cohort (22,693 included/735,000 total) were significantly different in most variables, yet similar in 30-day mortality rate (4.3-4.4%). Random forest models were developed on the ACSIS cohort with a full model including all 32 variables and a simple model including the 10 most important ones. Features' importance was calculated using the varImp function measuring how much each feature contributes to the data's homogeneity. Applying the optimized models on the MINAP validation cohort showed high discrimination of area under the curve (AUC) = 0.804 (0.786-0.822) for the full model, and AUC = 0.787 (0.748-0.780) using the simple model, compared with the GRACE risk score discrimination of AUC = 0.764 (0.748-0.780). All models were not well calibrated for the MINAP data. Following Platt scaling on 20% of the MINAP data, the random forest models calibration improved while the GRACE calibration did not change., Conclusions: The random forest predictive model for 30-day mortality post STEMI, developed on the ACSIS national registry, has been validated in the MINAP large external cohort and can be applied early at admission for risk stratification. The model performed better than the commonly used GRACE score. Furthermore, to the best of our knowledge, this is the first externally validated ML-based model for STEMI., (Copyright © 2021. Published by Elsevier Ltd.)

Background: The role of cardiovascular implantable electronic device (CIED)-derived activity to predict implantable cardioverter-defibrillator (ICD) therapy or death is not known., Objective: We aimed to assess CIED-derived activity to predict clinical outcomes., Methods: In 1500 patients enrolled in MADIT-RIT, CIED-derived patient activity was acquired daily, then averaged for the first 30 days following randomization to predict inappropriate/appropriate therapy or death. Kaplan-Meier analysis and Cox proportional regression models were used to evaluate inappropriate/appropriate therapy, heart failure, or death by 30-day CIED-derived patient activity quintiles., Results: There were 1463 patients with CIED activity data (98%). Patients in the highest quintile (Q5) of activity (more active) had the highest rate of inappropriate therapy, 21% at 2 years, as compared to 7%-11% in the other 4 quintiles (P < .001), a 1.75 times higher risk (95% confidence interval [CI]: 1.23-2.50, P = .002). However, patients in the lowest quintile of activity (Q1, 1 hour/day) had the highest risk of mortality, 15% in 2 years, as compared to Q2-3 (1-2 hours/day, 8%-7% mortality), and Q4-5 (>2 hours/day, 2%-3% mortality) (P < .001). Patients with the lowest level of activity (Q1) had a 2.02 times higher risk of mortality (95% CI: 1.21-3.38, P = .007), and they had an 82% higher risk of heart failure hospitalization (95% CI: 1.28-2.57, P = .001)., Conclusions: High CIED-derived 30-day median patient activity predicted inappropriate therapy, while low patient activity predicted mortality and heart failure in ICD and cardiac resynchronization therapy with defibrillator patients enrolled in MADIT-RIT. Device-derived activity assessment could serve as a useful predictor of outcomes., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Diastolic dysfunction (DD) might help to risk stratify patients with heart failure (HF) with reduced ejection fraction (HFrEF). Nonetheless, HF guidelines/risk scores don't consider DD. We aimed to show the independent prognostic value of DD for nonfatal HF/death in patients with HFrEF on top of natriuretic peptides (NP)., Methods: We analyzed 1155 baseline echocardiograms of the MADIT-CRT study (LVEF≤30%, QRS ≥ 130 ms, NYHA class I/II), classifying DD according to 2016 ASE/EACVI classification., Results: Patients were 64 ± 11 years-old, 24% females, LVEF was 24 ± 5%, 58% had abnormal BNP (≥100 pg/ml). While 45% had impaired relaxation, 33% had pseudonormal filling, 12% restrictive pattern, 6% indeterminate diastolic function, 4% were not classifiable due to missing data. During a follow-up of 2.1 ± 1.0 years, there were 233 HF/death. Compared to patients without pseudonormal/restrictive filling and with normal NP (23%), patients with pseudonormal/restrictive filling, alone (15%) or combined to elevated NP (30%), were at higher risk of events (respectively p adj = 0.025 and p adj < 0.001), as opposed to those with abnormal NP alone (22%; p adj = 0.55). Adding DD to conventional markers of risk and NP improved prediction (C-statistic 0.733 versus 0.708, p = 0.024). DD was the first parameter to be considered to risk stratify MADIT-CRT population, according to Classification-And-Regression-Tree analysis., Conclusions: Among HFrEF patients with mild symptoms, pseudonormal/restrictive filling, either alone or combined with elevated NP, was associated with high risk of events, as opposed to isolated elevation of NP. DD provided incremental risk prediction for death/HF beyond commonly used markers. These data might suggest to integrate DD into HF guidelines/risk scores., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cardiac resynchronization therapy-defibrillator (CRT-D) may reduce the incidence of first ventricular tachyarrhythmia (VTA) in patients with heart failure (HF) and left bundle branch block (LBBB)., Objective: The purpose of this study was to assess the effect of CRT-D on VTA burden in LBBB patients., Methods: We included 1281 patients with LBBB from MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy). VTA was defined as any treated or monitored sustained ventricular tachycardia (VT ≥180 bpm) or ventricular fibrillation (VF). Life-threatening VTA was defined as VT ≥200 bpm or VF. VTA recurrence was assessed using the Andersen-Gill model., Results: During a mean follow-up of 2.5 years, 964 VTA episodes occurred in 264 patients (21%). The VTA rate per 100 person-years was significantly lower in the CRT-D group compared with the implantable cardioverter-defibrillator (ICD) group (20 vs 34; P <.01). Multivariate analysis demonstrated that CRT-D treatment was associated with a 32% risk reduction for VTA recurrence (hazard ratio 0.68; 95% confidence interval 0.57-0.82; P <.001), 57% risk reduction for recurrent life-threatening VTA, 54% risk reduction for recurrent appropriate ICD shocks, and 25% risk reduction for the combined endpoint of VTA and death. The effect of CRT-D on VTA burden was consistent among all tested subgroups but was more pronounced among patients in New York Heart Association functional class I. Landmark analysis showed that at 2 years, the cumulative probability of death subsequent to year one was highest (16%) among patients who had ≥2 VTA events during their first year., Conclusion: In patients with LBBB and HF, early intervention with CRT-D reduces mortality, VTA burden, and frequency of multiple appropriate ICD shocks. VTA burden is a powerful predictor of subsequent mortality., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM) can lead to heart rhythm disturbances including complete heart block (CHB) and atrial and ventricular arrhythmias., Objective: We aimed to evaluate the utility of long-term arrhythmia monitoring with an implantable cardiac monitor (ICM) after ASA., Methods: Between February 2014 and March 2019, 56 patients with HCM undergoing ASA were enrolled in a prospective study and underwent ICM implantation. Kaplan-Meier survival analysis was used to assess the rate of ICM-detected arrhythmic events., Results: The mean age was 59 ± 11 years, and 20 (36%) were women. The median (25th, 75th percentile) resting left ventricular outflow tract gradient obtained by echocardiography was 43 (22, 81) mm Hg. Greater than 1 septal perforating artery was injected in 48 patients (86%). The Kaplan-Meier cumulative rate of ICM-detected arrhythmic events at 18 months of follow-up was 71%, with an event rate of 43% occurring within 3 months of ASA. The cumulative rate of the ICM-detected first atrial fibrillation event at 18 months was 37%, and the corresponding rate of CHB was 19%. All atrial fibrillation and CHB events were actionable, leading to the initiation of anticoagulation and pacemaker implantation, respectively. No baseline demographic or procedural variables were identified as independent predictors of an increased risk of developing ICM-detected arrhythmic events., Conclusion: After ASA, ICM is effective in capturing clinically actionable arrhythmic events in patients with HCM regardless of patient's baseline risk factors., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Life expectancy has increased in Israel during recent decades. However, compared to the majority, mostly Jewish population, life expectancy remains low among Israeli Arabs minority, and cardiovascular diseases are the leading cause of death. We compared baseline characteristics and outcomes between Israeli Arab and non-Arab patients hospitalized with acute coronary syndrome (ACS)., Methods and Results: A national survey accessed data of 7055 patients (1251, 18% Arabs) hospitalized with ACS. Compared to non-Arab, Arab patients were younger at ACS presentation (59 ± 11 vs. 65 ± 12 years, p < 0.01), more likely male (81% vs. 77%, p = 0.01), and with higher prevalence of diabetes mellitus (47% vs. 34%, p < 0.01) and smoking history (57% vs. 34%, p < 0.001). Among patients with ST-elevation myocardial infarction (STEMI) ACS, the mean time from first medical contact to the hospital was similar for Arab and non-Arab patients (133 and 137 min, respectively). After adjustment for age, gender, time from first medical contact to hospital arrival, diabetes, hypertension and renal failure, 1-year survival was lower among Arab patients (93.4% vs. 95.1%, p = 0.027), and 5-year survival was not statistically different (84.0% vs. 86.8%, p = 0.059). The survival differences were mostly derived from reduced survival at 1 and 5 years of STEMI Arab patients., Conclusions: Israeli Arabs present with ACS at a younger age than non-Arabs and have higher prevalence of smoking and diabetes at presentation. Adjusted 1-year survival was lower among Arab patients. Access to medical care and in-hospital practices during ACS were similar for Arabs and non-Arabs. The findings highlight the impact of risk factors on the early presentation of ACS and the need for a robust risk reduction program for Israeli Arabs., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/purpose: Patients with acute coronary syndrome (ACS) are at high-risk for recurrent coronary syndromes, heart failure and death. Early coronary intervention combined with medications reduces these risks. The ACS Israeli Survey (ACSIS) is conducted over a 2-month period, every 2-3 years. ACSIS includes all patients discharged with a diagnosis of ACS from the 24 coronary care units and cardiology departments in Israel. We compared clinical profiles and 1-year survival between ACS patients who did and did not undergo coronary angiography., Methods/materials: We reviewed ACSIS for the period 2002-2013., Results: The prognosis of patients who did not undergo coronary angiography during hospitalization (N = 2078) was significantly worse than for patients who underwent angiography (N = 9550). Avoidance of angiography was less common in ST-elevation myocardial infarction (STEMI) patients than in non-STEMI/unstable angina (NSTEMI/UAP) patients (13% vs. 22%, p < 0.001). Among NSTEMI/UAP patients, those who did not undergo angiography were older (mean: 71 vs. 64 years, p < 0.001), had higher incidences of diabetes (47% vs. 38%, p < 0.001), and renal (55% vs. 27%, p < 0.001) and heart failure (35% vs. 13%, p < 0.01) on admission, compared to those who underwent angiography. Even patients that underwent only diagnostic angiography had had a better prognosis than patients who did not undergo angiography. After propensity score matching for the major differences mentioned above, survival was still significantly better for patients who underwent angiography., Conclusion: ACS patients who did not undergo coronary angiography had higher-risk clinical profiles and worse 1-year survival than ACS patients who underwent angiography. After propensity score matching, the absence of angiography was independently associated with higher mortality., Summary: Data over 10 years were reviewed from a national registry of acute coronary syndrome. Patients who did not undergo coronary angiography during hospitalization were older and with more comorbidities than patients who underwent angiography. After propensity score matching, the absence of angiography remained independently associated with 1-year mortality., Competing Interests: Declaration of competing interest None declared., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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 p<0.001). 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) p<0.001]. NRI analysis showed an improvement of 21.5% (95%CI 18.3-25.1%) predicting 1-year mortality., Conclusion: 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., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The impact of sex on mortality in patients with acute heart failure (AHF) is unresolved. We aimed to investigate the impact of sex on both short- and long-term mortality outcomes after hospitalization for AHF., Methods: We analyzed data of 2,328 patients with AHF who were enrolled in the multicenter national survey in Israel between March and April 2003 and followed up until December 2014., Results: Women comprised 45% of the study population. In comparison with men, women were older, had higher rates of heart failure with preserved ejection fraction as well as hypertensive heart disease and had a lower rate of coronary artery disease (all P < 0.001). Survival analysis showed that at 1 year the rate of all-cause mortality was 31% among women compared to 28% among men (P = 0.19). At 10-year follow-up mortality rates were significantly higher among women compared to men (87% vs. 83%, P = 0.048). However, this sex association disappeared once multivariable analysis was carried out, (hazard ratio [HR] = 0.93; CI = 0.79-1.09, P = 0.36). Renal dysfunction, older age and severe heart failure were consistent independent predictors of mortality among men and women. Hyponatremia was a prognostic predictor only among men, whereas digoxin use predicted mortality only among women., Conclusions: There are important differences in the clinical characteristics between women and men hospitalized with AHF. There were no significant differences in both short- and long-term mortality following multivariable analysis. Although, most independent predictors of mortality were consistent among both sexes, few sex-based differences in prognostic predictors were identified., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Aims: Our aim was to investigate trends in prognosis among survivors of acute coronary syndrome according to left ventricular ejection fraction during a 16-year period., Methods: Data were derived from the Acute Coronary Syndrome Israeli Survey during the years 2000-2016. Patients aged 18 years and older were included in the analysis (N=11,725). Patients were classified into two groups based on their left ventricular ejection fraction: preserved (≥50%) and reduced (<50%) and also according to their acute coronary syndrome onset (2000-2006 early period vs. 2008-2016 late period). Endpoints were all-cause mortality rates at one and three years after the index event., Results: Preserved left ventricular ejection fraction was present in 5047/11,725 (43%) of patients. As expected, patients with preserved left ventricular ejection fraction had lower 1 and 3-year mortality rates as compared with reduced left ventricular ejection fraction regardless of the acute coronary syndrome period onset (6% vs. 19%, p<0.001). Nevertheless, in the late period the prevalence of reduced left ventricular ejection fraction decreased significantly, becoming equal to preserved left ventricular ejection fraction [2761 (50.5%) vs. 2713 (49.5%) respectively, p=0.3]. Moreover, prognosis during the late period as compared with the early period was improved only in patients with reduced left ventricular ejection fraction (HR 0.79; 95% CI 0.70-0.89, p=0.0001)., Conclusion: The prevalence of reduced left ventricular ejection fraction has decreased and prognosis has improved during the past several years but is still much worse than the prognosis of preserved left ventricular ejection fraction., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Studies of long-term inotrope use in advanced HF have previously provided limited and conflicting results. This study aimed to evaluate the safety and efficacy of long-term milrinone use and identify predictors of failure to bridge to orthotropic heart transplant (OHT) in a cohort of end-stage heart failure (HF) patients listed for heart transplantation and receiving inotrope therapy., Methods: The study included 150 adults listed for OHT at a single center from 2001 to 2017 who received milrinone therapy for ≥30 days. Multivariate Cox proportional hazards models were used to identify factors associated with "failure" (left ventricular assist device, intra-aortic balloon pump, status downgrade due to instability, death) vs. "success" (OHT, recovery) during bridging to OHT., Results: "Failure" occurred in 33 (22%) patients. Factors independently associated with failure included male sex (HR = 7.6; p = 0.004), no implantable cardioverter-defibrillator (HR = 3.8; p = 0.009), and lack of guideline-directed medical therapy (GDMT) with a beta-blocker (HR = 7.8; p = 0.002) or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (HR = 6.3; p < 0.001). Patients who received fewer guideline-directed medications had a higher cumulative probability of failure. Adverse events included central line-associated bloodstream infection (2.55 per 1000 line-days) and arrhythmia (1.59 per 1000 treatment-days)., Conclusions: Our findings suggest that long-term milrinone therapy in selected patients is associated with a high rate of successful bridging to OHT and a low rate of adverse events. Patients intolerant of GDMT are more likely to fail to bridge to OHT without mechanical support. Sex differences in outcomes associated with milrinone therapy should be explored., Competing Interests: Declaration of competing interest JTB receives research support from University of Rochester CTSA award number UL1 TR002001 from the National Center for Advancing Translational Sciences of the National Institutes of Health, and serves in an advisory role for AvantGarde Health. There is nothing to disclose for the other authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Atrial tachyarrhythmias (ATAs) are common among heart failure (HF) patients., Objective: The purpose of this study was to assess predictors for the development of new ATA and its components (atrial fibrillation/flutter [AF], supraventricular tachycardia [SVT]), and their association with subsequent clinical outcomes., Methods: We assessed predictors for first and recurrent ATA, AF, and SVT among 1500 patients in MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy). We also investigated the association of new ATA, AF, or SVT with subsequent ventricular arrhythmia (VA), adverse events (HF hospitalization, syncope, or death), or death by time-dependent analysis., Results: During 17 months of follow-up, 286 patients (19%) developed new ATA, of whom 92 (6%) had AF and 194 (12%) had SVT. Younger age (≤65 years), diastolic blood pressure ≥72 mm Hg, heart rate ≥63 bpm, absence of diabetes, and prior atrial arrhythmia were independent predictors of ATA. Prior atrial arrhythmia was the only predictor of AF (hazard ratio 3.14; P <.001). New ATA was associated with significantly increased risk for subsequent VA (HR 2.12; P <.001), increased adverse events (HR 1.42; P <.001), and death (HR 1.85; P = .038). New AF and new SVT were both independently associated with >2-fold increased risk for the development of subsequent VA (HR 2.21; P = .012l and HR 2.15; P <.001, respectively) and adverse events., Conclusion: Among MADIT-RIT patients, younger age, absence of diabetes, higher blood pressure, higher heart rate, and prior atrial arrhythmia predicted device-detected ATA. Both AF and SVT were associated with increased risk for subsequent VA and adverse events. Aggressive management should be considered in HF patients who develop new-onset, device-detected ATA to improve clinical outcomes., (Published by Elsevier Inc.)

Background: Left ventricular assist devices (LVADs) have improved outcomes for selected patients with advanced heart failure, but alternative optimal surgical techniques remain to be defined. We aim to describe our initial experience in using a sternal-sparing (SS) technique for implantation of a magnetically levitated LVAD, the HeartMate 3 (HM3) pump., Methods: This retrospective, single-center study included consecutive patients implanted with the HM3 LVAD between September 2015 and September 2018. Patients were compared based on surgical approach: SS or traditional sternotomy (TS). The primary outcome was overall survival at 6 months. Secondary outcomes included peri-operative complications, blood product utilization, and hospital readmissions., Results: Of 105 patients implanted with the HM3 LVAD, 41 (39%) were implanted via SS and 64 (61%) via TS approach. There were no intraoperative conversions. The SS patients were younger; otherwise, all other characteristics were similar between cohorts. The SS cohort demonstrated a significantly lower incidence of severe right ventricular failure (7% vs 28%, p = 0.012), fewer blood-product transfusions (41% vs 86%, p < 0.001), and shorter index hospital length of stay (15.5 vs 21 days, p = 0.018). Six-month survival was 93% for the SS cohort., Conclusions: In this single-center observational study, we have demonstrated that the SS approach may be a safe and effective surgical technique for implantation of the HM3 LVAD in well-selected patients. The potential benefits compared with TS require further inquiry., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The beneficial effect of statin therapy has been well established for both primary and secondary prevention of cardiovascular disease. Nevertheless, it remains under-used among patients with chronic kidney disease (CKD). We aimed to investigate the impact of statin therapy across a wide spectrum of CKD patients presenting with acute coronary syndrome (ACS)., Methods: We included all patients with ACS enrolled in the Acute Coronary Syndrome Israel Survey (ACSIS) between the years 2006 and 2016, and allocated them to 3 groups according to their renal function based on an estimated glomerular filtration rate (eGFR) calculation on admission (MDRD formula): eGFR<30 ml/min/1.73 m 2 (n = 525, 6%), eGFR 30-59 ml/min/1.73 m 2 (n = 1919, 21%), and eGFR>60 ml/min/1.73 m 2 (n = 6501, 73%). Primary outcome included in-hospital, 30-day, and 1-year major adverse cardiovascular events (MACE), and the independent prognostic effect of statins among CKD patients with ACS, by Cox regression analysis., Results: All 8945 consecutive ACS patients were included in our analysis. On hospital discharge, statin prescriptions were negatively associated with eGFR ]eGFR>60 ml/min/1.73 m 2 -95%, eGFR 30-59 ml/min/1.73 m 2 -90%, eGFR<30 ml/min/1.73 m 2 -78% (p < 0.001 for trend). Kaplan-Meier curves demonstrated both short and long-term higher mortality rates in those prescribed compared with those not prescribed statins (p < 0.001), regardless of renal function. Cox regression analysis revealed the protective effect of discharge statins (HR-0.25, 95% C.I 0.2-0.3, p < 0.001)., Conclusions: In our study, the beneficial effect of statins was maintained among CKD patients presenting with ACS. Therefore, these patients should be treated with statins regardless of their eGFR., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The clinical benefit of primary prevention implantable cardioverter-defibrillator (ICD) therapy in asymptomatic patients (New York Heart Association [NYHA] functional class I) with ischemic cardiomyopathy and left ventricular dysfunction is continually disputed., Objective: The purpose of this study was to evaluate the incidence of ventricular arrhythmias, mortality rates, and appropriate device therapies by NYHA class in a prospective national ICD registry., Methods: The study comprised 1670 consecutive patients with ischemic cardiomyopathy who were implanted with a primary prevention ICD and enrolled in the prospective national Israeli ICD Registry from 2010. The risk for clinical and arrhythmic events was assessed by NYHA class., Results: Asymptomatic patients (NYHA I) composed 19% of the study cohort. Comparison according to NYHA class showed that the highest mortality rate was in the NYHA III-IV group vs NYHA I and NYHA II (10.5% vs 5.4% and 5.8%, respectively; log rank P = .003). Conversely, cumulative incidence of appropriate ICD therapies, corrected for death as a competing risk, were higher among patients with NYHA I (11% vs 7%; P = .021). In a multivariate model, NYHA I vs ≥II remained independently associated with a significant 2-fold risk for appropriate ICD therapy (hazard ratio 2.03; 95% confidence interval 1.28-3.24)., Conclusion: Our findings indicate that patients with ischemic cardiomyopathy without heart failure symptoms have a higher risk of appropriate ICD therapy compared with symptomatic patients after adjustment for the competing risk of death, suggesting possible incremental benefit of primary ICD implantation in this population., (Copyright © 2019. Published by Elsevier Inc.)

Background: While women ≥80 years old have a high prevalence of coronary artery disease (CAD), little data exist regarding their outcome following acute coronary syndrome (ACS)., Methods: In a retrospective study based on data of 3518 ACS women patients who were enrolled in the ACS Israel Survey (ACSIS), we first evaluated and compared the clinical outcomes of 858 ACS women ≥80 years with 2660 ACS women <80 years, hospitalized during 2000-2016. Secondly, we evaluated the clinical outcome of 450 women ≥80 years hospitalized during 2000-2006 ('early period') and compared them with 408 ACS women of the same age group hospitalized during 2008-2016 ('late period')., Results: Implementation of the ACS AHA/ACC/ESC therapeutic guidelines was lower in ACS women ≥80 years compared with women <80 years. Multivariate Cox regression analysis demonstrated a worse 1-year survival rate in the ACS women ≥80 years compared with those <80 years. During the late period women ≥80 years were treated more frequently with guideline-recommended therapies compared with patients from the same age group who were hospitalized in the early period. A significant decline in in-hospital mortality rates in ACS women ≥80 years hospitalized in the late compared with the early period was demonstrated. However, 7-day, 30-day and 1-year mortality rates were not significantly changed., Conclusion: Adverse outcome rates of ACS women ≥80 years were significantly higher compared with those <80 years. In-hospital survival rates of ACS women patients ≥80 years improved during the 2000-2016 period; however, long-term survival rates were not significantly changed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: We sought to assess real-world implementation of the guidelines in patients with multivessel coronary artery disease (CAD) using a prospective national registry in Israel., Methods: All consecutive patients with left main or 2- to 3-vessel CAD involving the proximal or mid left anterior descending artery were enrolled in a dedicated multicenter registry. Patients were managed at the discretion of the treating team at each hospital and were followed for 30 months., Results: This registry included 1,064 patients, 55% treated with percutaneous coronary intervention (PCI) and 45% with coronary artery bypass surgery (CABG). Multivariate logistic regression analysis showed that chronic renal failure (odds ratio [OR], 2.43; p = 0.001) and prior myocardial infarction (OR, 1.7; p = 0.024) were associated with referral to PCI versus CABG, whereas male gender (OR, 2.27; p < 0.001), prior aspirin treatment (OR, 1.72; p = 0.005), diabetes mellitus (OR, 1.51; p = 0.007), 3-vessel CAD (OR, 3.45; p < 0.001) and SYNTAX score (SS) greater than 32 (OR, 10.0; p < 0.001) were associated with referral to CABG versus PCI. Each point increment in the SS was independently associated with a 9% greater likelihood of referral to CABG (p < 0.001). Survival analysis showed that mortality risk was lower among PCI patients less than 8 months after the procedure, and CABG was associated with a significant survival benefit thereafter., Conclusions: We found good agreement with current guidelines regarding revascularization strategies in real-world patients with multivessel CAD. The SS was the main independent predictor associated with the choice of revascularization strategy. The time-dependent association between revascularization strategy and long-term survival should be incorporated in the risk assessment of this population., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Use of the wearable cardioverter-defibrillator (WCD) in older patients has not been described previously., Objective: The purpose of this study was to assess WCD wear time, risk of arrhythmic events during WCD use, and implantable cardioverter-defibrillator (ICD) implantation rates after the end of WCD use in patients with age ≥65 years vs <65 years., Methods: We stratified 1732 patients with ischemic and nonischemic cardiomyopathy from the Prospective Registry of Patients Using the Wearable Defibrillator Registry into 2 subgroups by age: those with age ≥65 years and those with age <65 years. Wear time, arrhythmic events, and end-of-use decisions, specifically ICD implantation or improvement in ejection fraction, were evaluated for each age group., Results: There were 722 patients with age ≥65 years (41.7%) and 1010 patients with age <65 years (58.3%). Daily WCD wear time was longer in the older population (median 22.8 h/d (IQR 21.5 - 23.2) vs 22.3 h/d (IQR 19.5 - 23.0); P < .001). Patients with age ≥65 years experienced higher event rates, per 100 patient-years, for any sustained ventricular tachycardia/ventricular fibrillation (31.95 vs 9.82; P = .027) and ventricular tachycardia/ventricular fibrillation treated with WCD shock (6.92 vs 2.37; P = .034), particularly with ischemic cardiomyopathy. Younger patients experienced a trend toward a higher event rate for atrial arrhythmias with nonischemic cardiomyopathy (150.07 vs 74.86; P = .055). At the end of WCD use, ICD implantation was more frequent in older patients (41.8% vs 36.5%; P = .034)., Conclusion: Older patients had good compliance with the WCD, presented with more frequent ventricular arrhythmias, and were more likely to receive an ICD at the end of WCD use. The WCD may play a role in risk stratification of the older population., (Copyright © 2018. Published by Elsevier Inc.)

Aims: To determine the prevalence and mechanisms of de novo severe MR due to mitral valve structural abnormalities causing clinical deterioration in patients with HCM., Methods and Results: This is an observational study based on HCM registry comprising consecutive HCM patients (n=397) who have been evaluated and followed in the Cardiomyopathy Clinic of Sheba Medical Center. Sixteen patients (4.0%), 8 males, mean age 65±14 years, developed acute clinical deterioration due to development of severe mitral regurgitation unrelated to mitral valve systolic anterior motion. Compared to the remaining HCM population, those patients were older at their initial diagnosis (51±20 vs. 38±18 years) and more often females. Most frequently (in 10 patients, 63%) mitral regurgitation resulted from a flail posterior leaflet, while 4 patients had severe prolapse and 2 had isolated mitral annular/leaflet calcifications. Fourteen underwent surgery; myxomatous changes were found in all excised valves (n=9). On age-adjusted univariate analysis, 3 clinical parameters remained significantly associated with the development of de novo MR, female gender, LVOT obstruction and significant MR at baseline. On multivariable analysis, only LVOT obstruction (HR=3.8) and MR at baseline evaluation (HR=8.2) predicted development of severe MR., Conclusions: De novo severe MR leading to acute heart failure was repeatedly observed in our HCM series. This etiology needs to be considered as a cause of acute clinical deterioration in these patients., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Malignancy and diabetes mellitus (DM) cause significant morbidity and mortality after heart transplantation (HTx). Metformin, one of the most commonly used anti-diabetic drugs worldwide, has also been shown to exhibit anti-tumor activity. We therefore investigated the association between metformin therapy and malignancy after HTx., Methods: The study population comprised 237 patients who underwent HTx between 1991 and 2016 and were prospectively followed-up. Clinical data were recorded on prospectively designed forms. The primary outcome was any cancer recorded during 15 years of follow-up. Treatment with metformin and the development of DM after HTx were assessed as time-dependent factors in the analyses., Results: Of the 237 study patients, 85 (36%) had diabetes. Of the DM patients, 48 (56%) were treated with metformin. Kaplan-Meier survival analysis showed that, at 15 years after HTx, malignancy rate was 4% for DM patients treated with metformin, 62% for those who did not receive metformin and 27% for non-DM patients (log-rank test, p < 0.0001). Consistently, multivariate analysis showed that for DM patients, metformin therapy was independently associated with a significant 90% reduction (hazard ratio = 0.10; 95% confidence interval 0.02 to 0.40; p = 0.001) in the risk of the development of a malignancy. DM patients who were treated with metformin had a markedly lower risk (65%; p = 0.001) for the development of a malignancy or death after HTx as compared with non-DM patients., Conclusions: Our findings suggest that metformin therapy is independently associated with a significant reduction in the risk of malignancy after HTx., (Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Risk scores for prediction of mortality 30-days following a ST-segment elevation myocardial infarction (STEMI) have been developed using a conventional statistical approach., Objective: To evaluate an array of machine learning (ML) algorithms for prediction of mortality at 30-days in STEMI patients and to compare these to the conventional validated risk scores., Methods: This was a retrospective, supervised learning, data mining study. Out of a cohort of 13,422 patients from the Acute Coronary Syndrome Israeli Survey (ACSIS) registry, 2782 patients fulfilled inclusion criteria and 54 variables were considered. Prediction models for overall mortality 30days after STEMI were developed using 6 ML algorithms. Models were compared to each other and to the Global Registry of Acute Coronary Events (GRACE) and Thrombolysis In Myocardial Infarction (TIMI) scores., Results: Depending on the algorithm, using all available variables, prediction models' performance measured in an area under the receiver operating characteristic curve (AUC) ranged from 0.64 to 0.91. The best models performed similarly to the Global Registry of Acute Coronary Events (GRACE) score (0.87 SD 0.06) and outperformed the Thrombolysis In Myocardial Infarction (TIMI) score (0.82 SD 0.06, p<0.05). Performance of most algorithms plateaued when introduced with 15 variables. Among the top predictors were creatinine, Killip class on admission, blood pressure, glucose level, and age., Conclusions: We present a data mining approach for prediction of mortality post-ST-segment elevation myocardial infarction. The algorithms selected showed competence in prediction across an increasing number of variables. ML may be used for outcome prediction in complex cardiology settings., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Limited, contradictory data exist regarding the effect of hyperkalemia on both short- and long-term all-cause mortality among hospitalized patients with heart failure (HF)., Methods: We analyzed 4,031 patients who were enrolled in the Heart Failure Survey in Israel. The study patients were grouped into 3 different potassium (K) categories. Multivariate analysis was used to determine the association of potassium levels as well as 1- and 10-year all-cause mortality., Results: A total of 3,349 patients (83%) had K < 5mEq/L, whereas 461 patients (11%) had serum K ≥ 5mEq/L but≤ 5.5mEq/L and 221 patients (6%) had K > 5.5mEq/L. Survival analysis showed that 1-year mortality rates were significantly higher among patients with K > 5.5mEq/L (40%) and those with serum K ≥ 5mEq/L but ≤ 5.5mEq/L (34%) compared to those with K < 5mEq/L (27%); (all log rank P < 0.01). Similarly, 10-year mortality rates among those with K > 5.5mEq/L were 92%, whereas among those with serum K ≥ 5mEq/L but ≤ 5.5mEq/L rates were 88%, and in those with K < 5mEq/L rates were 82%; (all log rank P < 0.001). Consistently, multivariate analysis showed that compared to patients with K < 5mEq/L, patients with K > 5.5mEq/L had an independently 51% and 31% higher mortality risk at 1 year and 10 years, respectively (1-year hazard ratio = 1.51, 95% CI: 1.04-2.2; 10-years hazard ratio = 1.31, 95% CI: 1.035-1.66), whereas patients with serum K ≥ 5mEq/L but ≤ 5.5mEq/L had comparable adjusted mortality risk to patients with K < 5mEq/L at 1 and 10 years., Conclusions: Among hospitalized patients with HF, admission K > 5.5mEq/L was independently associated with increased short- and long-term mortality, whereas serum K ≥ 5mEq/L but ≤ 5.5mEq/L was not independently associated with worse outcomes., (Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Introduction: Recent new therapeutic options have improved outcomes of acute coronary syndrome (ACS) patients. However, data regarding the incremental effect of the improved treatment on patients with renal dysfunction are limited. We sought to evaluate temporal trends in management and outcome of ACS patients according to renal function., Methods: The study population consisted of all ACS patients enrolled in the Acute Coronary Syndromes Israeli Survey (ACSIS) during 2002-2013. Patients were categorized as normal renal function, mild to moderate and severe renal insufficiency. Patient's characteristics, clinical data and outcomes were compared in each group between 2 time frames - early (2002-2006) vs. late (2008-2013)., Results: The study population included 11,234 patients. Regardless of renal function, patients enrolled in the recent surveys were more frequently selected for an invasive approach and were more commonly treated with guideline-based therapy. Among patients with normal renal function or mild to moderate renal dysfunction the improvement in treatment was associated with a significant reduction in 5-year mortality (10.1% vs. 12.6%, p=0.004, and 36% vs. 41.9%, p=0.01, respectively). On the other hand, outcomes of patients with severe renal insufficiency were unchanged. Multivariate analysis showed that reperfusion was associated with 41% mortality reduction in patients with mild to moderate renal insufficiency (HR=0.59 CI 95 0.48-0.72, p<0.01%)., Conclusions: Treatment of ACS patients has improved over the past decade. Treatment improvement was associated with a significant mortality reduction in patients with normal renal function and mild to moderate renal dysfunction but not in patients with severe renal dysfunction., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Consuming desalinated seawater (DSW) as drinking water (DW) may reduce magnesium in water intake causing hypomagnesemia and adverse cardiovascular effects., Methods: We evaluated 30-day and 1-year all-cause mortality of acute myocardial infarction (AMI) patients enrolled in the biannual Acute Coronary Syndrome Israeli Survey (ACSIS) during 2002-2013. Patients (n=4678) were divided into 2 groups: those living in regions supplied by DSW (n=1600, 34.2%) and non-DSW (n=3078, 65.8%). Data were compared between an early period [2002-2006 surveys (n=2531) - before desalination] and a late period [2008-2013 surveys (n=2147) - during desalination]., Results: Thirty-day all-cause-mortality was significantly higher in the late period in patients from the DSW regions compared with those from the non-DSW regions (HR=2.35 CI 95% 1.33-4.15, P<0.001) while in the early period there was no significant difference (HR=1.37 CI 95% 0.9-2, P=0.14). Likewise, there was a significantly higher 1-year all-cause mortality in the late period in patients from DSW regions compared with those from the non-DSW regions (HR=1.87 CI 95% 1.32-2.63, P<0.0001), while in the early period there was no significant difference (HR=1.17 CI 95% 0.9-1.5, P=0.22). Admission serum magnesium level (M±SD) in the DSW regions (n=130) was 1.94±0.24mg/dL compared with 2.08±0.27mg/dL in 81 patients in the non-DSW (P<0.0001)., Conclusions: Higher 30-day and 1-year all-cause mortality in AMI patients, found in the DSW regions may be attributed to reduced magnesium intake secondary to DSW consumption., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Both resting blood pressure (BP) variability and exercise BP previously showed association with incident hypertension. The aim of the present study was to examine whether visit-to-visit variability in exercise systolic blood pressure (SBP) can predict the risk for new-onset hypertension among normotensive adults. We investigated 6546 normotensive men and women who were annually screened in a tertiary medical center and completed treadmill exercise tests at each visit. Based on the initial three baseline annual visits, long-term intervisit variability of exercise SBP among the three tests was measured using standard deviation (SD) and coefficient of variation for each participant. The rate of newly diagnosed hypertension was measured in different variability levels during 6 ± 3 years of follow-up. Multivariate analysis adjusted for various clinical factors, including resting BP, showed that each 5 mm Hg rise in the SD of exercise SBP resulted in a significant 5% increase in the risk for the development of future hypertension (P = .015). Subjects in the upper exercise SBP SD variability tertile had a 28% (P = .007) increased risk for hypertension during follow-up, as compared with those in the lowest tertile. Similar results were achieved for the assessment of coefficient of variation of exercise SBP. In conclusion, visit-to-visit variability in exercise SBP can predict the development of future hypertension among normotensive individuals., (Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: STEMI is thought to occur as a result of a vulnerable coronary plaque rupture. Statins possess hypolipidemic and pleotropic effects that stabilize coronary plaque. We sought to determine the association between LDL-C levels, statin use prior to the index event on the type of acute coronary syndrome (ACS) presentation: STEMI vs. non-STEMI/unstable angina., Methods: Data was drawn from the ACS Israeli Survey (ACSIS), a biennial prospective survey of ACS patients hospitalized in all CCU/Cardiology departments during 2002-2010., Results: Among 6790 patients, 2760 (41%) reported statin use prior to the index ACS event. The proportion of STEMI was significantly lower among statin treated vs. statin naive patients (36% vs. 57%, p<0.0001). At each LDL-C level, the proportion of STEMI was significantly lower only among statin treated patients (p<0.0001). LDL-C<70 mg/dL was associated with a lower proportion of STEMI only among statin treated but not among statin naive patients (33% vs. 57%, p<0.0001). Multivariate analysis revealed that statin use was independently associated with a lower probability of presenting with STEMI (ORadj=0.73, p=0.007), but not LDL-C<70 mg/dL (ORadj=1.13, p=0.32). Patients on high-intensity statin therapy (HIST) were less likely to present with STEMI as compared with low-intensity statin therapy (LIST) or statin naive patients (27%, 38%, 56%, respectively, p for trend <0.0001; HIST ORadj=0.28, p=0.01; LIST ORadj=0.48, p=0.026)., Conclusions: Among patients admitted with ACS, statin use but not LDL-C level, was associated with a lower probability of presenting with STEMI. Patients on HIST had the lowest likelihood of presenting with STEMI., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: There are limited data about the correlation between brain natriuretic peptide (BNP) levels and arrhythmic risk assessment in patients who receive device therapy for the treatment of heart failure (HF) or for the prevention of sudden cardiac death., Objectives: We aimed to investigate the association between BNP levels and the risk of ventricular tachyarrhythmias among mildly symptomatic HF patients who receive an intracardiac defibrillator (ICD) with or without cardiac resynchronization therapy (respectively, CRT-D or CRT)., Methods: The study population involved 1197 patients enrolled in MADIT-CRT. Plasma BNP was measured in a core laboratory at baseline and after 1-year follow-up. Ventricular tachycardia/fibrillation (VT/VF) events were identified from ICD/CRT-D interrogations., Results: Multivariate Cox hazards regression modeling showed that elevated baseline (> median = 72 ng/L) and 1-year BNP were associated with a significant increase in the risk of VT/VF (HR = 1.36, P = .026; and HR = 1.79, P < .001, respectively); and VT/VF or death (HR = 1.37, P = .008; and HR = 1.84, P < .0001, respectively) during follow-up. At 1 year post device implantation, BNP levels were significantly lower among study patients treated with CRT-D as compared with those who received ICD only (P = .014). CRT-D patients who had greater than median reductions in BNP levels (greater than one-third reduction of initial value) experienced a significantly lower risk of subsequent VT/VF (HR = 0.61, P = .021) and VT/VF or death (HR = 0.45, P < .0001) as compared to patients without such reductions., Conclusions: In MADIT-CRT, elevated baseline and follow-up BNP levels were independent predictors of increased risk for subsequent ventricular tachyarrhythmias, whereas BNP reductions following CRT-D implantation identified patients with a lower incidence of VT/VF during follow-up., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: There is limited data regarding the relationship between age and inappropriate therapy among patients with an implantable cardioverter-defibrillator (ICD) and resynchronization therapy., Objectives: We aimed to investigate this relationship and the effect of ICD programming on inappropriate therapy by age., Methods: In the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) 1500 patients were randomized to 3 ICD programming arms: (A) conventional with ventricular tachycardia (VT) therapy ≥170; (B) high-rate cutoff with VT therapy ≥200, and (C) prolonged 60-second delay for VT therapy ≥170. We investigated the relationship between age, the risk of inappropriate ICD therapy (including antitachycardia pacing [ATP] or shock), and ICD programming., Results: Cumulative incidence function Kaplan-Meier graphs showed an inverse relationship between increasing quartiles of age (Q1: ≤55, Q2: 56-64, Q3: 65-71, and Q4: ≥72 years) and the risk for inappropriate therapy. Multivariate analyses showed that each increasing decade of life was associated with 34% (P < .001), 27% (P < .001), and 26% (P < .001) reduction in the risk of inappropriate shock, inappropriate ATP, and any inappropriate therapy, respectively. Treatment arms B and C as compared with arm A were associated with a significant reduction in the risk of inappropriate therapies across all age quartiles (P < .001 for all)., Conclusions: Among patients with a primary prevention indication for an ICD, there is an inverse relationship between age and inappropriate ICD therapy. Innovative ICD programming of high-rate cutoff or prolonged delay for VT therapy is associated with significant reductions in inappropriate therapy among all age groups., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Implantable cardioverter-defibrillators (ICDs) have become the mainstay of preventive measures for sudden cardiac death (SCD). However, there are limited data on rates of appropriate life-saving ICD shock therapies in contemporary real-life settings., Objective: The purpose of the study was to evaluate the rate of appropriate life-saving ICD shock therapies in a contemporary registry., Methods: The Israeli ICD Registry includes all implants and other ICD operative procedures nationwide. The present study comprises 2349 consecutive cases who were enrolled in the Registry and prospectively followed up for information regarding survival, hospitalizations, and ICD therapies since 2010., Results: Kaplan-Meier survival analysis showed that the rate of appropriate ICD shock therapy at 30-month follow-up was 2.6% among patients who received an ICD for primary prevention compared with 7.4% among those who received a device for secondary prevention (log-rank P < .001). Rates of appropriate ICD shocks among primary prevention patients were 1.1% at 1-year of follow-up and 2.6% at 30 months, whereas the corresponding rates in the secondary prevention group were 3.8% at 1 year and 7.4% at 30 months (log-rank P < .001). A total of 253 patients (4.8%) died during follow-up, 65% of noncardiac causes., Conclusion: Rates of life-saving appropriate ICD shock therapies among patients implanted with a defibrillator for the primary prevention of SCD in a contemporary real-world setting are lower than reported previously. These findings suggest a need for improved risk stratification and patient selection in this population., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to examine whether imaging of the atrioventricular (AV) membranous septum (MS) by computed tomography (CT) can be used to identify patient-specific anatomic risk of high-degree AV block and permanent pacemaker (PPM) implantation before transcatheter aortic valve implantation (TAVI) with self-expandable valves., Background: MS length represents an anatomic surrogate of the distance between the aortic annulus and the bundle of His and may therefore be inversely related to the risk of conduction system abnormalities after TAVI., Methods: Seventy-three consecutive patients with severe aortic stenosis underwent contrast-enhanced CT before TAVI. The aortic annulus, aortic valve, and AV junction were assessed, and MS length was measured in the coronal view., Results: In 13 patients (18%), high-degree AV block developed, and 21 patients (29%) received a PPM. Multivariable logistic regression analysis revealed MS length as the most powerful pre-procedural independent predictor of high-degree AV block (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.1 to 1.7, p = 0.01) and PPM implantation (OR: 1.43, 95% CI: 1.1 to 1.8, p = 0.002). When taking into account pre- and post-procedural parameters, the difference between MS length and implantation depth emerged as the most powerful independent predictor of high-degree AV block (OR: 1.4, 95% CI: 1.2 to 1.7, p < 0.001), whereas the difference between MS length and implantation depth and calcification in the basal septum were the most powerful independent predictors of PPM implantation (OR: 1.39, 95% CI: 1.2 to 1.7, p < 0.001 and OR: 4.9, 95% CI: 1.2 to 20.5, p = 0.03; respectively)., Conclusions: Short MS, insufficient difference between MS length and implantation depth, and the presence of calcification in the basal septum, factors that may all facilitate mechanical compression of the conduction tissue by the implanted valve, predict conduction abnormalities after TAVI with self-expandable valves. CT assessment of membranous septal anatomy provides unique pre-procedural information about the patient-specific propensity for the risk of AV block., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Because of its safety profile, cryoablation has become an alternative therapy for septal arrhythmias, including parahisian accessory pathways (APs). Data regarding its efficacy, safety, and late outcome for parahisian APs in children are limited., Objective: The purpose of this study was to evaluate the safety and efficacy of cryoablation of parahisian APs in children., Methods: Fifty-nine cryoablations of parahisian APs were performed in 50 patients [76% males; median age 16.5 years (range 5.3-20 years)]. Thirty-three had manifest APs and 17 had concealed APs. The time to effect was defined as the duration of time from reaching -30°C to the disappearance of AP during the cryomapping phase. The acute success rate for the first ablation was 94% (47/50)., Results: Mean fluoroscopy time and number of cryoablations were 28.5 ± 23.3 minutes and 2.6 ± 1.2 seconds, respectively. The time to effect was 8.5 ± 7.1 seconds. The overall recurrence rate was 14.9%, decreasing from 40% in the first 10 cases to 8.1% in the next 37 (P <.02). Multivariate analysis showed that the only independent predictor for recurrence rate was time to effect <10 seconds (P <.001). A high recurrence rate was also associated with concealed APs and ablation during supraventricular tachycardia (P <.03 and P <.05, respectively). The patients who had recurrence underwent a second successful cryoablation. During median follow-up of 59.7 months (range 6-102 months), a long-term success rate of 94% was achieved. No permanent ablation-related complications occurred., Conclusion: Cryoablation of parahisian APs has excellent short- and long-term efficacy and safety profile. Increased physician experience is associated with a reduced recurrence rate., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve implantation (TAVI) has become the treatment of choice for the symptomatic patients with aortic stenosis (AS) and high surgical risk. Pulmonary hypertension (PHTN) has been shown to be associated with worse early and late outcomes after aortic valve surgery. Data regarding the effect of TAVI on PHTN are limited., Methods and Results: We evaluated the characteristics and outcome of the patients with various degrees of systolic PHTN referred for TAVI. PHTN was defined as systolic pulmonary arterial pressure (SPAP) ≥50mmHg as assessed by echocardiography. The patients with SPAP decrease after TAVI to below 50mmHg were compared to the patients with persistent PHTN following TAVI. Of the 122 patients included in the present study, 49 (40%) patients had elevated SPAP prior to TAVI. This group of patients presented with smaller aortic valve areas, greater degrees of mitral or tricuspid regurgitation, lower left ventricular ejection fraction, and more prevalent chronic obstructive pulmonary disease (COPD) (all p<0.05). Following TAVI, 57% of the patients with prior PHTN experienced a reduction in SPAP to below 50mmHg. Multivariable analysis identified COPD to be the most powerful predictor for PHTN presence post-TAVI (hazard ratio 3.9, 95% confidence interval 1.5-9.9, p=0.005). Post-TAVI PHTN (SPAP ≥50mmHg) was associated with a 3.4-fold, independent, 2-year mortality risk (p=0.04)., Conclusions: Our data suggest that TAVI is associated with a significant reduction in pulmonary pressure in more than half of the patients with preprocedural PHTN. COPD identifies the patients with persistent PHTN after TAVI. Post-TAVI PHTN is associated with markedly worse outcome., (Copyright © 2014. Published by Elsevier Ltd.)

In patients with acute coronary syndrome (ACS), the predictive potential of admission systolic blood pressure (SBP) on early and late outcomes is not entirely clear. We investigated the association between admission SBP in patients hospitalized for ACS and subsequent morbidity and mortality in a real world setting. The study population comprised 7645 ACS patients enrolled in the Acute Coronary Syndromes Israeli Survey (ACSIS) between 2002 and 2010. We analyzed the association between admission SBP, and the rates of 7-day and 1-year all-cause mortality and of 30-day major cardiovascular adverse events (MACE). Admission SBP was categorized as low (<110 mm Hg), normal (110-140 mm Hg), high (141-160 mm Hg), and very high (>160 mm Hg). Compared with patients with normal admission SBP, those with low SBP had a significantly increased hazard ratios (HRs) for 7-day and 1-year mortality, and MACE of 2.37, 1.92, and 1.51, respectively (all P < .001). In contrast, patients with very high admission SBP had significantly decreased HRs for 7-day and 1-year mortality, and MACE of 0.46, 0.65, and 0.84, respectively (P = .004, <.001, and .07, respectively). In patients with ACS, elevated admission SBP is associated with favorable early and late outcomes., (Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background/objectives: In the past diabetes was strongly associated with elevated mortality rate after acute coronary syndrome (ACS). Over the past decade a treatment of the ACS has evolved rapidly with major advances in the management techniques. The aim of the present study was to compare temporal trends of the outcomes of diabetic vs. non-diabetic patients using nationwide data., Methods: We evaluated time-dependent changes in the clinical characteristics, management strategies, and outcomes of diabetic and non-diabetic patients enrolled in the biannual ACS Israeli Surveys (ACSIS) between 2000 and 2010. We divided the survey into early (2000-2005) vs. late (2006-2010) periods., Results: There were 3964 diabetic and 7322 non-diabetic patients, a total of 11,472 ACS patients. Although diabetic patients were significantly younger, they displayed more advanced coronary artery disease and considerably higher rates of all-cause mortality at 30 days and 1-year. Both diabetic and non-diabetic patients who were enrolled in the late survey period received more evidence-based therapies (primary PCI, guideline-based medications) and experienced a better 1-year survival probability (respectively 88% vs. 84% and 93% vs. 90%; all p-values<0.01). Multivariate analysis demonstrated that diabetes and early survey period were each independently associated with a significantly increased mortality risk (respectively 39% and 25%, p<0.001 for both)., Conclusion: Our data suggest that despite the overall improvement in the management and outcomes of the ACS, diabetic patients are still at increased residual risk of long-term mortality that needs to be further addressed., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Coronary CT has become the foremost noninvasive imaging modality for detecting coronary stenoses in patients with suspected coronary artery disease. Nevertheless, little is known about its performance in patients undergoing transcatheter aortic valve replacement (TAVR)., Objective: This study investigates the diagnostic performance of coronary CT angiography in patients referred for TAVR., Methods: One hundred and fifteen consecutive patients with severe aortic stenosis underwent CT angiography with retrospective electrocardiography triggered acquisition and an iterative reconstruction algorithm, of whom 23 (20%) had prior coronary artery bypass graft (CABG) surgery. Diagnostic accuracy of CT for detecting significant coronary stenosis (≥ 50% luminal diameter stenosis in segments ≥ 2 mm) in the left main, proximal, or middle segments of coronary arteries and bypass grafts was compared with that of invasive coronary angiography., Results: In the overall study population, the sensitivity, specificity, and positive and negative predictive value of CT angiography for the detection of coronary segment or bypass graft lesions were 96% (47 of 49), 73% (48 of 66), 72% (47 of 65), and 96% (48 of 50), respectively. The per-patient diagnostic yield of CT angiography was consistent among patients without prior CABG (93% [28 of 30], 73% [45 of 62], 62% [28 of 45], and 96% [45 of 47], respectively) and among patients with prior CABG (100% [19 of 19], 75% [3 of 4], 95% [19 of 20], and 100% [3 of 3], respectively)., Conclusion: Among patients referred for TAVR, coronary CT angiography with retrospective gating and iterative reconstruction may allow detection of significant stenosis in the proximal or middle segments of coronary arteries and could permit the evaluation of patients after bypass grafts., (Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Over the past decade, the development of novel management strategies has resulted in improved outcomes among patients hospitalized with ST-segment myocardial infarction (STEMI). The aim of the present study was to compare temporal trends in the mortality of smokers versus non-smokers admitted with STEMI in a real world setting between 2000 and 2010., Methods: We evaluated time-dependent changes in the clinical characteristics, management strategies, and one year all-cause mortality of STEMI patients who were enrolled in the biannual Acute Coronary Syndrome Israeli Survey (ACSIS) between 2000 and 2010, categorized as smokers (n=2399) and non-smokers (n=3069). We divided the survey periods into early (2000-2004) and late (2006-2010). The primary endpoint of the study was the occurrence of one-year all-cause mortality., Results: A total of 4564 STEMI patients were enrolled in the study. Compared with non-smokers, smokers were significantly younger and displayed a significantly lower rate of all-cause mortality at 30 days and 1-year. Both smokers and non-smokers who were enrolled in the late survey period received more evidence-based therapies (primary PCI and guideline-based medications) (p<0.001 for all). There was a significant reduction in the risk of 1-year all-cause mortality only among non-smokers (HR=0.664 CI 95% 0.52-0.85, p=0.0009), whereas smokers who were enrolled in more recent survey periods did not display a significant risk reduction (HR=1.08 CI 95% 0.77-1.51, p=0.67)., Conclusion: Survival following STEMI among smokers has not improved over the past decade despite corresponding changes in management strategies. Future trials should focus on reducing the risk in smokers., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: There are no prior studies assessing the relationship between left atrial volume (LAV) and inappropriate implantable cardioverter-defibrillator (ICD) therapy following treatment with cardiac resynchronization therapy., Objective: The purpose of this study was to investigate the hypothesis that patients randomized to cardiac resynchronization therapy with defibrillator (CRT-D) in the Multicenter Automatic Defibrillator Trial-Cardiac Resynchronization Therapy (MADIT-CRT) who had significant LAV reductions would have reduced risks of inappropriate ICD therapy., Methods: Cardiac resynchronization remodeling was assessed by measuring LAV change between baseline and 12-month echocardiograms in 751 CRT-D treated patients. Patients were stratified into quartiles based on percent reduction of LAV change. High LAV responders were those in the highest 3 quartiles of LAV reduction (LAV reduction ≥21%). Low LAV responders were those in the lowest quartile of LAV reduction (LAV reduction <21%). Clinical factors associated with ≥21% reduction in LAV were evaluated by linear regression analysis., Results: In Cox proportional hazards regression analyses, high LAV responders had a 39% reduction in the risk of inappropriate therapy (hazard ratio 0.61, P = .04) and left bundle branch block patients exhibited an even greater risk reduction in inappropriate therapy (hazard ratio 0.51, P = .02) compared to low LAV responders during follow-up extending up to 3 years after the 12-month echocardiogram. High LAV responders also had a significantly lower risk of heart failure or death during follow-up than did low LAV responders., Conclusion: A ≥21% reduction in LAV with cardiac resynchronization therapy is associated with significant reductions in inappropriate ICD therapy and in heart failure or death during a 3-year follow-up., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Defibrillation threshold (DFT) testing during placement of an implantable cardioverter-defibrillator (ICD) has been considered mandatory. Accumulating data suggest a more limited role for DFT., Objective: The purpose of this study was to compare the outcome of ICD recipients who underwent DFT testing compared with those who did not., Methods: In this prospective cohort analysis of patients who received an ICD between July 2010 and March 2013, we compared patients who underwent DFT testing and those who did not. Primary end-points were death and malignant ventricular arrhythmias. Secondary end-points included the composite end-points and inappropriate ICD discharges., Results: Of the 3596 patients in the registry, 614 patients (17%) underwent DFT testing during ICD placement vs 2982 (83%) who did not. Variables associated with ICD testing were implantation for secondary prevention (relative risk [RR] 1.87), prior ventricular arrhythmias (RR 1.81), use of antiarrhythmic medication (RR 1.59), and sinus rhythm (RR 2.05). Factors predisposing against testing were cardiac resynchronization therapy defibrillator implantation (RR 0.56) and concomitant diuretic use (RR 0.71). ICD testing was not associated with 1-year mortality (5.3% vs 5.1%, P = .74), delivery of appropriate shocks (8.6% vs 5.6%, P = .16), combined outcomes of ventricular arrhythmias and death (12.9% vs 11.3%, P = .45), or inappropriate ICD discharges (3.9% vs 2.1%, P = .2) compared to no DFT testing., Conclusion: No significant differences in the incidence of mortality, malignant ventricular arrhythmias, or inappropriate ICD discharges were observed between patients who underwent DFT testing compared to those who did not. Our results may support avoiding DFT testing during ICD placement, but this requires confirmation by additional prospective studies., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Limited data exist regarding the proarrhythmic effects of smoking., Objective: To evaluate the relationship between smoking and the risk of first and recurrent ventricular tachyarrhythmias (VTAs) in patients with mild heart failure., Methods: The risk of a first and recurrent appropriate implantable cardioverter-defibrillator therapy for VTAs or death was compared between nonsmokers (n = 465), past smokers (n = 780), and current smokers (n = 197) in patients with ischemic and nonischemic cardiomyopathy who were enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy study., Results: The cumulative probability of a first VTA or death was significantly higher in current smokers than in past and nonsmokers (P < .001). Multivariate analysis showed that current smokers had a significantly higher risk of first ventricular tachycardia/ventricular fibrillation or death (hazard ratio [HR] 1.51; 95% confidence interval [CI] 1.14-2.01; P = .005) and a higher risk for first ventricular tachycardia/ventricular fibrillation episode (HR 1.54, 95% CI 1.12-2.13, P = .008) than did nonsmokers. Past smokers had a risk of first VTAs or death similar to that of nonsmokers (HR 1.01; 95% CI 0.80-1.27; P = .953). In comparison to nonsmokers, the risk of recurrent VTAs was significantly higher in the total cohort of patients (HR 1.54; 95% CI 1.21-1.95; P < .001) and in the subgroups of patients with ischemic and nonischemic cardiomyopathy (HR 1.48; 95% CI 1.03-2.13; P = .035)., Conclusions: Current smokers with left ventricular dysfunction and mild heart failure are at a significantly higher risk of VTAs or death than are past smokers and nonsmokers. Smoking is associated with a significant increase in the risk of recurrent VTAs in both patients with ischemic and nonischemic cardiomyopathy., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: High-density lipoprotein cholesterol (HDL-C) is a strong inverse predictor of cardiovascular events. The aim of the current study was to evaluate the correlation between changes in HDL-C and subsequent cardiovascular events., Methods: Study population comprised 13,037 subjects free of cardiovascular disease with a mean follow up of 6 ± 3 years. Low HDL-C was defined as < 40 mg/dl for men and <50mg/dl for women. Participants were divided into three groups based on HDL-C levels at the first and second baseline visits: persistently-low HDL-C (LL); persistently-high HDL-C (HH); and those with high HDL-C in a one visit only: intermittently high HDL-C (LH/HL). The primary endpoint was the first occurrence of a cardiovascular event., Results: A total of 529 (4.1%) incident events occurred during follow-up. HDL-C levels increased significantly between the two landmark visits (47.5 ± 12.6 vs. 48.1 ± 12.2, p<0.001). Kaplan-Meier survival analysis showed that the cumulative probability of cardiovascular events at 6 years was highest among subjects in the LL group (7.6%), and similar among LH/HL and HH groups (3.3% and 4%, respectively; log-rank p=0.001). Multivariate Cox regression analysis, with HDL-C as time-dependent covariate, showed that subjects with persistently low HDL-C during follow up experienced a 51% increased cardiovascular risk compared with subjects with persistently high HDL-C (p=0.026). Subjects with intermittently high HDL-C during follow up experienced similar risk to those with persistently high HDL-C (HR=1.02; p=0.89)., Conclusions: Variations in HDL-C levels during follow-up are associated with subsequent cardiovascular risk. Patients who retain low HDL-C levels are at the cardiovascular highest risk., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)