Safety of High-Dose Dabigatran in Elderly and Younger Patients with a Low Bleeding Risk: A Prospective Observational Study.

INTRODUCTION: In patients with atrial fibrillation (AF) at risk for stroke, dabigatran 150 mg twice a day (DE150) is superior to warfarin for stroke prevention. However, there is paucity of data with respect to bleeding risk at this dose in elderly patients (≥75 years). We aimed to evaluate the safety of DE150 in comparison to warfarin in a real-world population with AF and low bleeding risk (HAS-BLED score ≤2). METHODS: In this prospective observational study, 754 consecutive patients with AF and HAS-BLED score ≤2 were included. We compared outcome of elderly patients (age ≥75 tears) to younger patients (age <75 years). The primary end point was the combined incidence of all-cause mortality, stroke, systemic emboli, and major bleeding event during a mean follow-up of 1 year. RESULTS: There were 230 (30%) elderly patients, 151 patients were treated with warfarin, and 79 were treated with DE150. Fifty-two patients experienced the primary endpoint during the 1-year follow-up. Among the elderly, at 1-year of follow-up, the cumulative event rate of the combined endpoint in the DE150 and warfarin was 8.9 and 15.9% respectively (p = 0.14). After adjustment for age and gender, patients who were treated with DE150 had a nonsignificant difference in the risk for the combined end point as patients treated with warfarin both among the elderly and among the younger population (HR 0.58, 95% C.I = 0.25-1.39 and HR = 1.12, 95% C.I 0.62-2.00, respectively [p for age-group-by-treatment interaction = 0.83). CONCLUSIONS: Our results suggest that Dabigatran 150 mg twice a day can be safely used among elderly AF patients with low bleeding risk.

Body mass index and the risk of new-onset atrial fibrillation in middle-aged adults.

BACKGROUND: Increased body mass index (BMI) and obesity are associated with increased risk of new-onset atrial fibrillation (AF) among middle-aged adults. OBJECTIVES: The objective of the study is to investigate the association between BMI and the risk for new-onset AF among middle-aged adults. METHODS: We investigated 18,290 men and women who were annually screened in a tertiary medical center. Participants were divided at baseline into 3 groups: normal weight (BMI ≥18 and <25 kg/m(2), n = 7,692), overweight (BMI ≥25 and <30 kg/m(2), n = 8,032), and obese (BMI ≥30 kg/m(2), n = 2,566). The primary end point was new-onset AF during follow-up. RESULTS: Mean age of study population was 49 ± 11 years, and 73% were men. A total of 288 incident events (1.6%) occurred during 6 ± 4 years. Kaplan-Meier survival analysis showed that the cumulative probability of AF at 6 years was highest among obese participants, intermediate among overweight participants, and lowest among participants with normal weight (2.1%, 1.7%, and 0.8% respectively, P < .001). Multivariable Cox regression analysis showed that overweight and obesity were independently associated with increased AF risk (hazard ratio 1.54 [P = .004] and 2.41 [P < .001], respectively). Assessment of BMI change as a time-dependent covariate in the multivariable model showed that each 1 kg/m(2) reduction in BMI during follow-up was associated with a significant 7% reduction in the risk for the occurrence of a first AF event (hazard ratio 0.93, 95% CI 0.88-0.99, P = .019). Consistently, similar analysis showed that each 5-kg weight loss during follow-up was independently associated with a significant 12% reduced risk of new-onset AF (95% CI 0.81-0.98, P = .02). CONCLUSIONS: Our findings suggest that overweight and obesity are associated with increased AF risk, whereas weight reduction is independently associated with reduced risk of de novo AF.

Bezafibrate for the treatment of dyslipidemia in patients with coronary artery disease: 20-year mortality follow-up of the BIP randomized control trial.

BACKGROUND: Recent data support the renewed interest in hypertriglyceridemia as a possible important therapeutic target for cardiovascular risk reduction. This study was designed to address the question of all-cause mortality during extended follow-up of the BIP trial in patients stratified by baseline triglyceride levels. METHODS: In the BIP trial 3090 patients with proven coronary artery disease were randomized to bezafibrate 400 mg/day or placebo. All-cause mortality data after 20 years of follow-up, were obtained from the National Israeli Population Registry. Patients with hypertriglyceridemia (triglycerides ≥200 mg/dL, n = 458) were equally distributed among the study groups (15 % in both placebo and bezafibrate groups). RESULTS: During follow-up 1869 patients died (952 in placebo vs. 917 in bezafibrate group). Following multivariate adjustment allocation to bezafibrate was associated with small but significant 10 % mortality risk reduction (HR 0.90; 95 % CI 0.82-0.98, p = 0.026). Variables associated with significantly increased mortality risk were history of a past MI, NYHA class, diabetes, age, higher BMI and glucose level. In patients with hypertriglyceridemia multivariate analysis demonstrated a 25 % all-cause mortality risk reduction associated with allocation to bezafibrate (HR 0.75, CI 95 % 0.60-0.94; p = 0.012). In patients without hypertriglyceridemia bezafibrate had no significant effect on long-term mortality. CONCLUSIONS: During long-term follow-up bezafibrate-allocated patients experienced a modest but significant 10 % reduction in the adjusted risk of mortality. This effect of bezafibrate was more prominent among patients with baseline hypertriglyceridemia (25 % mortality risk reduction).

The association between cardiorespiratory fitness and cardiovascular risk may be modulated by known cardiovascular risk factors.

BACKGROUND: We aimed to evaluate whether reduced cardiovascular fitness has a direct or indirect effect for the development of cardiovascular disease. METHODS: We investigated 15,595 men and women who were annually screened in a tertiary medical center. All subjects were free of ischemic heart disease and had completed maximal exercise stress test according to the Bruce protocol at their first visit. Fitness was categorized into age- and sex-specific quintiles (Q) according to Bruce protocol treadmill time with Q1 as lowest fitness. Subjects were categorized at baseline into 3 groups: low fitness (Q1), moderate fitness (Q2-Q4), and high fitness (Q5). The primary end point of the current analysis was the development of a first cardiovascular event during follow-up. RESULTS: Mean age of study patients was 48 ± 10 years, and 73% were men. A total of 679 events occurred during 92,092 person-years of follow-up. Kaplan-Meier survival analysis showed that the cumulative probability of cardiovascular events at 6 years was significantly higher among subjects with low fitness (P < .001). Low fitness was associated with known cardiovascular risk factors, including hypercholesterolemia (odds ratio [OR] 1.58, 95% CI 1.31-1.89), diabetes mellitus (OR 2.32, 95% CI 1.58-3.41), and obesity (OR 10.46, 95% CI 8.43-12.98). The effect of low fitness on cardiovascular events was no longer significant when including diabetes mellitus, hypercholesterolemia, and obesity as mediators (hazard ratio 0.99, 95% CI 0.82-1.19). CONCLUSIONS: The association between cardiovascular fitness and adverse cardiovascular outcomes may be modulated through traditional cardiovascular risk factors. These findings need to be further validated in prospective clinical trials.

Impaired fasting glucose and left ventricular diastolic dysfunction in middle-age adults: a retrospective cross-sectional analysis of 2971 subjects.

BACKGROUND: Left ventricular (LV) diastolic dysfunction (LVDD) is a well-established and early echocardiographic characteristic of diabetic cardiomyopathy. However, there are limited data on the association between impaired fasting glucose (IFG) and LVDD. OBJECTIVE: To determine whether IFG is associated with LVDD among middle age adults. METHODS: Amongst 3781 subjects screened in an annual health survey program and referred for an echocardiogram, 2971 individuals without LV systolic dysfunction or valvular heart disease were selected. Mean age of study population was 59 ± 12 years and 75% were men. The subjects were categorized into three groups: euglycemia (N = 2025), IFG (N = 534) and diabetes mellitus (DM; N = 412). Doppler echocardiography readers were blinded to glycemic state. Subjects with impaired LV relaxation, pseudo-normal or restrictive filling patterns were defined as having LVDD. RESULTS: LVDD was diagnosed in 574 (19 %) of subjects and it was more prevalent among patients with IFG and DM than in euglycemic individuals (27, 30 and 15%, respectively; p < 0.001). Patients with IFG and DM had lower ratios of early (E) to late (A) trans-mitral flow (0.9 ± 0.3 and 0.9 ± 0.3 vs. 1.1 ± 0.4, respectively, p < 0.001). LV hypertrophy (LVH) was also more prevalent among patients with IFG and DM (11 and 18%, respectively, vs. 9%; p < 0.001). Multivariate binary logistic regression model adjusted to age, gender, obesity, LVH, renal function, total, high and low density lipoprotein cholesterol, triglycerides, ischemic heart disease, hypertension and LV ejection fraction showed that patients with IFG were 43% more likely to have LVDD compared with euglycemic subjects (95% confidence interval 1.12-1.83, p = 0.004). CONCLUSIONS: IFG is independently associated with a significant increase in the likelihood for the presence of LVDD in middle aged adults.

Clinical impact of diabetes mellitus in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Diabetes mellitus (DM) and aortic stenosis (AS) are frequent findings in the elderly population. Data regarding the influence of DM on the outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) due to AS are limited. The aim of this study was to examine the impact of DM on TAVR outcomes. METHODS: We investigated 443 patients with severe AS undergoing TAVR. Subjects were divided into insulin-dependent diabetic mellitus (IDDM) patients (N = 44), non-dependent insulin diabetic mellitus (NIDDM) patients (N = 114) and non-diabetics (N = 285) of whom 31 (74%), 86 (79%) and 209 (76%) respectively had trans-femoral TAVR. Peri-procedural complications and outcomes were recorded according to the Valve Academic Research Consortium-2 criteria. RESULTS: Patients with IDDM as well as NIDDM demonstrated similar complication rates compared with non-diabetic patients, except for acute kidney injury (AKI) grade 3 [4 (2%) and 3 (3%) vs. 1 (0.4%) respectively, p = 0.032]. Kaplan-Meier survival analysis showed that DM, regardless of the type of treatment, was not associated with increased 2 years mortality (Log-rank p value 0.44). Multivariate cox regression analysis adjusted for age, gender, coronary artery disease, DM, AKI3, hypertension, chronic renal failure and peripheral vascular disease found that AKI3 was associated with increased risk of 2 years mortality [HR = 7.35, 95% CI 2.16-25.07, p = 0.001] whereas female gender was found as a protective factor [HR = 0.47, 95% CI 0.28-0.8, p = 0.005], and DM was not associated with increased risk. CONCLUSIONS: Following TAVR, DM patients seem to have similar peri-procedural and mid-term outcomes compared with patients without DM, while IDDM patients seem to suffer greater incidence of AKI. Further research in larger cohorts of patients is needed to validate our results.

Diagnostic and prognostic value of very high serum lactate dehydrogenase in admitted medical patients.

BACKGROUND: Serum lactate dehydrogenase (LDH) is elevated in various diseases. OBJECTIVES: To analyze serum LDH as a distinguishing clinical biomarker and as a predictor of in-hospital outcome in admitted medical patients. METHODS: We analyzed a cohort of all 158 patients with very high isolated LDH (LDH > or = 800 IU/ml without concomitant elevations of alanine aminotransferase and aspartate aminotransferase) admitted to our internal medicine department during a 3 year period. Epidemiologic and clinical data, as well as the final diagnosis and outcome were recorded and compared with those of a cohort of all 188 consecutive control patients. RESULTS: Very high isolated LDH was a distinguishing biomarker for the presence of cancer (27% vs. 4% in the LDH group and controls respectively, P < 0.0001), liver metastases (14% vs. 3%, P < 0.0001), hematologic malignancies (5% vs. 0%, P = 0.00019), and infection (57% vs. 28%, P < 0.0001). Very high isolated LDH was a marker for severe prognosis, associated with more admission days (9.3 vs. 4.1, P < 0.0001), significantly more in-hospital major complications, and high mortality rate (26.6% vs. 4.3%, P < 0.0001). Finally, very high isolated LDH was found in a multivariate regression analysis to be an independent predictor of mortality. CONCLUSIONS: The presence of very high isolated LDH warrants thorough investigation for the presence of severe underlying disease, mostly metastatic cancer, hematologic malignancies, and infection. Moreover, it is a marker for major in-hospital complications and is an independent predictor of mortality in admitted medical patients. lactate dehydrogenase (LDH), cancer, internal medicine

Implantable Cardioverter Defibrillator for the Primary Prevention of Sudden Cardiac Death among Patients With Cancer.

Data are limited regarding the characteristics and outcomes of patients with cancer who are found eligible for primary defibrillator therapy. We performed a single-center retrospective analysis of patients with preexisting cancer diagnoses who become eligible for a primary prevention implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) defibrillator. Multicenter Automatic Defibrillator Implantation Trial-ICD (MADIT-ICD) benefit scores were calculated. The study included 75 cancer patients at a median age of 73 (interquartile range 64, 81) years at heart failure diagnosis. Active cancer was present in 51%. Overall, 55% of the cohort had coronary artery disease and 37% were CRT eligible. We found that 48%, 49%, and 3% of cohorts had low, intermediate, and high MADIT-ICD Benefit scores, respectively. Only 27% of patients underwent primary defibrillator implantation. Using multivariate analysis, indication for CRT and intermediate/high MADIT-ICD Benefit categories were found as independent predictors for implantation (odds ratio 8.42 p <0.001 and odds ratio 3.74 p = 0.040, respectively). During a median follow-up of 5.3 (interquartile range 4.5, 7.2) years, one patient (5%) with a defibrillator had appropriate shock therapy and 2 patients (10%) had bacteremia. Of 13 patients with CRT defibrillator-implants, one patient was admitted for heart failure exacerbation (8%). Using a time-varying covariate model, we did not observe statistically significant differences in the survival of patients with cancer implanted versus those not implanted with primary defibrillators (hazard ratio 0.521, p = 0.127). In conclusion, although primary defibrillator therapy is underutilized in patients with cancer, its relative benefit is limited because of competing risk of nonarrhythmic mortality. These findings highlight the need for personalized cardiologic and oncologic coevaluation.

Biodegradable polymer drug-eluting stents versus durable polymer drug-eluting stents for percutaneous coronary intervention: a contemporary registry-based analysis.

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

Albumin as a Prognostic Marker for Atrial Fibrillation Recurrence following Cryoballoon Ablation of Pulmonary Venous.

Introduction: Atrial fibrillation (AF) recurrence following pulmonary vein isolation (PVI) ablation has clinical significance. Identifying risk factors for AF recurrence is important. We investigated serum albumin (SA) levels (g/dL) as a prognostic factor for the recurrence of AF following cryoballoon PVI ablation. Methods: We included patients who underwent cryoballoon PVI ablation at our institution between the years 2013 and 2018. The primary outcome was recurrence of AF during follow up. Results: Our cohort consisted of 126 patients (67% males, mean age 61.8 ± 10.0 years). The pattern of AF amongst the cohort was paroxysmal in 62.5%, persistent in 25.4%, and longstanding persistent in 6.3%. Those with lower SA levels had a mean AF duration significantly less than those with higher SA levels (2.81 years, 7.34 years, and 6.37 years for SA levels of <3.8, 3.8−4.1, and ≥4.1, respectively; p = 0.003). Patients with lower SA levels were significantly more likely to have had more previous cardioversions and a larger left atrial area and volume. The mean follow-up was 380 days, in which the AF recurrence rate was 20.6%. Patients with lower SA level had significantly more AF recurrences (47.4%, 16.7%, and 2.2% for SA levels of <3.8, 3.8−4.1, and ≥4.1, respectively; p < 0.001). Upon multivariate analysis, an SA level < 3.8 was associated with a higher risk of AF recurrence (OR = 5.422 95% CI 1.134; 25.910; p < 0.001). Conclusion: SA levels were found to be a strong independent marker for AF recurrence following PVI ablation.

Epicardial fat and the risk of atrial tachy-arrhythmia recurrence post pulmonary vein isolation: a computed tomography study.

Epicardial and Pericardia fat have been hypothesized to exert local and systemic pathogenic effects on nearby cardiac structures. The present study aimed to evaluate the impact of epicardial and pericardial fat volumes on the outcome of patients that underwent a first pulmonary vein isolation (PVI) with cryoablation. We included 130 consecutive patients with atrial fibrillation (AF) that underwent contrast enhanced ECG-gated cardiac computed tomography (CCT) before a PVI. The control group included 50 patients in normal sinus rhythm that underwent ECG-gated CT to rule out coronary artery disease. Epicardial and pericardial fat volumes were quantified with CCT. Patients with AF compared to patients with normal sinus rhythm (control group) had significantly larger epicardial (140.3 ± 58.1 vs. 55.9 ± 17.7 ml; respectively, P < 0.001) and pericardial (77.0 ± 35.5 ml vs. 27.2 ± 9.5 ml; respectively, P < 0.001) fat volumes. Among patients that underwent PVIs, those with AF recurrence had a greater epicardial (175.0 ± 54.4 ml vs. 130.7 ± SD 54.2 ml; respectively, P < 0.001) and pericardial (93.7 ± SD 42.8 vs. 72.5 ± SD 31.9 ml; respectively, P < 0.001) fat volumes, compared to patients with no AF recurrence. Multivariate analyses revealed that epicardial fat was an independent predictor of recurrence post-ablation (HR = 1.08, 95% CI 1.02-1.16 per 10-ml increase in volume; P = 0.009). Pericardial fat was associated with 7% increase in risk of recurrent AF (HR = 1.07, 95% CI 0.98-1.18; P = 0.117). Epicardial fat, assessed with contrast enhanced CCT, is an independent predictor of AF recurrence after PVI ablation.

Permanent His-bundle pacing using stylet-directed, active-fixation leads placed via coronary sinus sheaths compared to conventional lumen-less system.

BACKGROUND: The use of coronary sinus (CS) sheaths to deliver stylet-driven leads (SDLs) for His-bundle pacing (HBP) has not been described. Conventionally, HBP is achieved using a stylet-less lead delivered through a customized catheter. OBJECTIVE: The purpose of this study was to characterize the acute and early-term HBP experience with stylet-driven, active-fixation leads delivered through CS sheaths compared to the conventional approach. METHODS: Delivery of Medtronic 4471 and 7742 SDLs was attempted in 27 patients. Delivery was facilitated using CS guide catheters and custom-shaped stylets. Procedural characteristics and lead performance were compared to those of a group of 17 patients in whom delivery of 3830 lumen-less leads (LLLs) was attempted. Patients had heterogeneous pacing indications. RESULTS: HBP with SDL was successful in 24 of 27 patients(89%) compared to 15 of 17 patients (88%) in the LLL group. Mean procedural and fluoroscopy times in the SDL and LLL groups were 129 ± 43 minutes vs 104 ± 43 minutes and 9.6 ± 5.2 minutes vs 8.3 ± 5.0 minutes, respectively (both P = NS). There was a significant difference in procedure and fluoroscopy times within the SDL group between the first and second halves of the series, probably secondary to a learning curve. Acute HBP thresholds were higher with SDL than with LLL (2.6 ± 1.5 V vs 1.5 ± 1.2 V; P = .02) and remained stable at 8.4 ± 5.3 months. Both SDLs exhibited similar pacing thresholds. Two crossovers between groups occurred (1 in each group). Four patients with SDL and 1 patient with LLL exhibited high thresholds during follow-up. CONCLUSION: Permanent HBP using stylet-driven, active-fixation leads delivered through conventional CS sheaths is feasible. Procedural characteristics and lead performance were clinically acceptable.

Direct Visualization of the His Bundle Pacing Lead Placement by 3-Dimensional Electroanatomic Mapping: Technique, Anatomy, and Practical Considerations.

BACKGROUND: His bundle pacing (HBP) remains technically challenging and is currently guided by electrograms and 2-dimensional fluoroscopy. Our objective was to describe a new technique for HBP directly guided by electroanatomic mapping (EAM). METHODS: Twenty-eight patients were included. The atrioventricular septum was mapped via EAM, and His bundle (HB) electrograms, selective, and nonselective HB capture sites were tagged. Pacing leads were connected to EAM, navigated to tagged HB target sites and deployed. Intracardiac electrograms and pacing parameters were recorded. Lead location was tagged on the cloud of HB sites, which was divided into 3 arbitrary segments. In 5 patients, atrioventricular nodal ablation was performed with direct visualization of the HBP lead by EAM. RESULTS: Reproducible navigation of the pacing lead to predetermined HBP locations guided by EAM was achieved in all patients. The lead was successfully deployed in 25 patients. HB cloud area was 360 (212) mm2. There was no correlation between HBP threshold and lead location on the His cloud. The intracardiac electrograms atrial/ventricular ratio at the lead deployment site correlated with its EAM position on the His cloud ( P=0.045). Procedure, fluoroscopy, and mapping times were 116.0 (38.8), 8.6 (6.3), and 9.0 (11.4) minutes, respectively. HBP threshold at implant was 1.5 (2.3) V at 1.5 (1.0) ms. Distance between HB lead and ablation sites was 10.0 (1.3) mm in patients undergoing atrioventricular nodal ablation. CONCLUSIONS: Direct guidance of HBP by EAM allows for direct visualization of the pacing lead on the HB cloud and reproducible navigation to predetermined HB capture sites. Intracardiac electrograms atrial/ventricular ratio at the lead deployment site correlates with His cloud location. EAM can be applied during standard HBP procedures or combined with atrioventricular nodal ablation.

Effect of supplemented intake of omega-3 fatty acids on arrhythmias in patients with ICD: fish oil therapy may reduce ventricular arrhythmia.

PURPOSE: The aim of this study was to evaluate the effects of fish oils, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on ventricular tachyarrhythmic episodes (VTEs) in implantable cardioverter defibrillator (ICD) recipients with ischemic cardiomyopathy. METHODS: One hundred five ICD recipients with ischemic cardiomyopathy received 3.6 g of EPA and DHA and placebo for 6 months, each at a random order, with a 4-month washout period between treatments. Eighty-seven patients completed the 16-month study protocol. The primary end point was any VTE (including sustained and non-sustained ventricular tachycardias at a rate of >150 bpm) as recorded by the ICDs. Secondary end points included device therapy (anti-tachycardia pacing (ATP) or shocks). RESULTS: During treatment with fish oils, there was a significant increase in EPA and DHA concentrations in red blood cells (RBCs) and subcutaneous fat tissue. Among 87 patients who completed the study protocol, the mean number of VTEs was significantly lower during treatment with fish oil (1.7) vs. placebo (5.6; p = 0.035). Appropriate device therapy for VTE occurred in 18 (21%) patients. Fish oil therapy was associated with a trend toward fewer VTEs terminated with ATP (2.8 ± 13.7 vs. 0.5 ± 2.1, respectively; p = 0.077). VTE terminated by ICD shocks, however, was rare, and rates were similar between both groups (0.11 ± 0.6 vs. 0.10 ± 0.4, p = not significant, respectively). CONCLUSIONS: Our data suggest that fish oil therapy may be associated with a reduction in the frequency of VTE in ICD recipients with ischemic cardiomyopathy.

Temporal trends and outcomes associated with atrial fibrillation observed during acute coronary syndrome: Real-world data from the Acute Coronary Syndrome Israeli Survey (ACSIS), 2000-2013.

BACKGROUND: The past decade has brought major advances in therapy of patients presenting with acute coronary syndromes (ACS). HYPOTHESIS: The outcomes of ACS patients with atrial fibrillation (AF) has improved over the years. METHODS: We evaluated time-dependent changes in clinical characteristics, management strategies, and outcomes associated with AF observed during ACS hospitalization in patients enrolled in the biannual ACS Israeli Surveys (ACSIS) between 2000 and 2013. We divided the surveys into early (2000-2006) and late (2008-2013) time periods. RESULTS: The study population comprised 13 297 ACS patients, of whom 755 (5.7%) either presented with or developed AF during the index hospitalization. The incidence of AF observed during ACS hospitalization was lower during the later period (6.2% vs 4.9%; P < 0.01). Kaplan-Meier survival analysis showed that 1-year mortality rates were significantly lower among ACS patients with and without AF who were enrolled during the later vs early survey period (log-rank P < 0.01 for the overall difference). However, AF observed among ACS patients was still associated with increased risk for in-hospital complications and 30-day and 1-year mortality during both the early and late survey periods (P < 0.05 for all comparisons). CONCLUSIONS: In 10 years, rates of AF among ACS patients have declined significantly. Yet, despite improved overall 1-year survival for patients with AF, the development of AF in this population remains an independent predictor of mortality that has not changed appreciably over the years.

Chewing versus Swallowing Ticagrelor to Accelerate Platelet Inhibition in Acute Coronary Syndrome - the CHEERS study. For The PLATIS (Platelets and Thrombosis in Sheba) Study Group.

It was the study objective to evaluate whether chewing a 180 mg loading dose of ticagrelor versus an equal dose of traditional oral administration, enhances inhibition of platelet aggregation 1 hour (h) after administering a ticagrelor loading dose in non-ST elevation myocardial infarction (NSTEMI) patients. Dual anti-platelet therapy represents standard care for treating NSTEMI patients. Ticagrelor is a direct acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Fifty NSTEMI patients were randomised to receive either a chewing loading dose of 180 mg ticagrelor or an equal standard oral dose of ticagrelor. Platelet reactivity was evaluated by VerifyNow at baseline, 1 and 4 h post-loading dose. Results are reported in P2Y12 reaction units. Patients then continued to receive standard 90 mg oral ticagrelor twice daily. Baseline characteristics did not differ between the two groups. P2Y12 reaction units in the chewing group compared with the standard group at 0, 1 and 4 h after ticagrelor loading dose were: 245 vs 239 (p=0.59), 45 vs 130 (p=0.001) and 39 vs 60 (p=0.12), respectively, corresponding to a relative inhibition of platelet aggregation of 83 % vs only 47 % at 1 h (p< 0.001), and 84 % vs 77 % (p=0.59) at 4 h. Major adverse cardiac and cardiovascular events at 30 days were low (2 %), occurring in only one patient in the standard group. In conclusion, chewing a 180 mg ticagrelor loading dose is feasible and facilitates both faster and improved early inhibition of platelet aggregation in NSTEMI patients, compared with a standard oral-loading dose.

Elevated Triglyceride Level Is Independently Associated With Increased All-Cause Mortality in Patients With Established Coronary Heart Disease: Twenty-Two-Year Follow-Up of the Bezafibrate Infarction Prevention Study and Registry.

BACKGROUND: The independent association between elevated triglycerides and all-cause mortality among patients with established coronary heart disease is controversial. The aim of this study was to investigate this association in a large cohort of patients with proven coronary heart disease. METHODS AND RESULTS: The study cohort comprised 15 355 patients who were screened for the Bezafibrate Infarction Prevention (BIP) trial. Twenty-two-year mortality data were obtained from the national registry. Patients were divided into 5 groups according to strata of fasting serum triglycerides: (1) low-normal triglycerides (<100 mg/dL); (2) high-normal triglycerides (100-149 mg/dL); (3) borderline hypertriglyceridemia triglycerides (150-199 mg/dL); (4) moderate hypertriglyceridemia triglycerides (200-499 mg/dL); (5) severe hypertriglyceridemia triglycerides (≥500 mg/dL). Age- and sex-adjusted survival was 41% in the low-normal triglycerides group than 37%, 36%, 35%, and 25% in groups with progressively higher triglycerides (P<0.001). In an adjusted Cox-regression for various covariates including high-density lipoprotein cholesterol, each 1 unit of natural logarithm (Ln) triglycerides elevation was associated with a corresponding 6% (P=0.016) increased risk of 22-year all-cause mortality. The 22-year mortality risk for patients with severe hypertriglyceridemia was increased by 68% when compared with patients with low-normal triglycerides (P<0.001). CONCLUSIONS: In patients with established coronary heart disease, higher triglycerides levels are independently associated with increased 22-year mortality. Even in patients with triglycerides of 100 to 149 mg/dL, the elevated risk for death could be detected than in patients with lower triglycerides levels, whereas severe hypertriglyceridemia denotes a population with particularly increased mortality risk.

Short and long term survival following hospitalization with a primary versus non-primary diagnosis of acute heart failure.

OBJECTIVE: To compare the short-term and long-term outcomes of patients hospitalized with a primary diagnosis of acute heart failure (AHF) versus AHF associated with an alternative principal diagnosis. METHODS: The Israel nationwide Heart Failure (HF) survey examined prospectively 4102 consecutive HF patients admitted to all 25 public hospitals in the country. This study focused on 2302 patients hospitalized with a diagnosis of AHF. In 1594 patients, AHF was the principal diagnosis of hospitalization. In 708 patients, AHF was a secondary diagnosis with an alternative principal diagnosis of hospitalization. RESULTS: Patients with secondary diagnosis of AHF were younger with an overall less comorbidities except for concomitant ischemic heart disease. Despite that, hospital duration was longer (median days (Q1-Q3), 4 (3-7), and 6(4-9), respectively, P<0.001) and in-hospital mortality was higher (7.2% vs. 4.9%, p-value=0.03) among patients with a secondary diagnosis of AHF. Consistently, the age and sex adjusted OR of secondary diagnosis of AHF for in-hospital mortality was 1.76 (C.I. 1.2-2.54; p-val=0.003). However, long-term follow-up showed a risk-reversal wherein the adjusted risk for 10-year mortality was significantly lower among those hospitalized with a secondary vs. primary diagnosis of AHF (HR=0.88, C.I. 0.79-0.99; p-val=0.04). CONCLUSIONS: While hospitalization with secondary diagnosis of AHF is associated with a higher risk for in-hospital mortality in comparison to hospitalization with principal diagnosis of AHF, it is independently associated with a lower risk for 10-year mortality. These findings may have implications for short and long term risk stratification after AHF hospitalization.