Is syncope a risk predictor in the general population?

Syncope in the general population is a frequent event often leading to hospitalization, but it is unclear whether syncope in the general population is an independent risk marker for adverse prognosis. In this review, we investigate the current literature and evaluate the prognosis and impact of syncope on adverse outcomes including death and recurrences across different populations with focus on the general population. In wide terms, a syncopal event is related to a higher risk of subsequent falls and injury and cardiac syncope is particularly associated with increased mortality as compared to non-cardiac syncope. The overall prognosis in the general population is by large determined by the underlying presence and severity of a given cardiac disease, but a given underlying cardiac disease can very well be unknown at the time of first syncope so that syncope is the presenting symptom resulting in an independent risk increase. Moreover, syncope is a significant risk predictor of a recurrence across populations. It is im­portant to recognize several risk factors associated with adverse outcome in order to safely navigate in a population where most patients with syncope are healthy and low-risk but where a small number of patients have life-threatening conditions. Further research in the general population should attempt to categorize which patients with syncope need immediate referral and diagnostic testing, and whether this affects the outcome

Impact of Carvedilol and Metoprolol on Inappropriate Implantable Cardioverter-Defibrillator Therapy The MADIT-CRT Trial (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy)

ObjectivesThe goal of this study was to evaluate the effects of carvedilol and metoprolol on the endpoint of inappropriate implantable cardioverter-defibrillator therapy in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy) study.BackgroundThe impact of carvedilol and metoprolol on inappropriate therapy in heart failure patients with devices has not yet been investigated.MethodsAll patients in the MADIT-CRT study who received a device (N = 1,790) were identified. Using time-dependent Cox regression analysis, we compared patients treated with different types of beta-blockers or no beta-blockers on the primary endpoint of inappropriate therapy, delivered as antitachycardia pacing (ATP) or shock therapy. Secondary endpoints were inappropriate therapy due to atrial fibrillation and atrial tachyarrhythmias, also evaluated as ATP or shock therapy.ResultsInappropriate therapy occurred in 253 (14%) of 1,790 patients during a follow-up period of 3.4 ± 1.1 years. Treatment with carvedilol was associated with a significantly decreased risk of inappropriate therapy compared with metoprolol (hazard ratio [HR]: 0.64 [95% confidence interval (CI): 0.48 to 0.85]; p = 0.002). The reduction in risk was consistent for inappropriate ATP (HR: 0.66 [95% CI: 0.48 to 0.90]; p = 0.009) and inappropriate shock therapy (HR: 0.54 [95% CI: 0.36 to 0.80]; p = 0.002). The risk of inappropriate therapy caused by atrial fibrillation was also reduced in patients receiving carvedilol compared with metoprolol (HR: 0.50 [95% CI: 0.32 to 0.81]; p = 0.004). General use of beta-blockers (93%) and adherence in this study was high.ConclusionsIn heart failure patients undergoing either cardiac resynchronization therapy with a defibrillator or with an implantable cardioverter-defibrillator device, carvedilol was associated with a 36% lower rate of inappropriate ATP and shock therapy compared with metoprolol. Inappropriate therapy due to atrial fibrillation was associated with a 50% lower rate in patients receiving carvedilol compared with those receiving metoprolol. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271

Clinical Impact, Safety, and Efficacy of Single- versus Dual-Coil ICD Leads in MADIT-CRT

BACKGROUND: Current data on efficacy, safety and impact on clinical outcome of single- versus dual-coil implantable cardioverter-defibrillator (ICD) leads are limited and contradictory. METHODS: Defibrillation threshold (DFT) at implantation and first shock efficacy were compared in patients implanted with single- versus dual-coil ICD leads in MADIT-CRT. The risk for atrial tachyarrhythmias and all-cause mortality were evaluated. Short- (< 30 days after the implantation) and long-term (throughout the entire study duration) complications were assessed. RESULTS: Patients with dual-coil ICD leads had significantly lower DFTs compared to patients with single-coil ICD leads (17.6 +/- 5.8 J vs 19.4 +/- 6.1 J, P < 0.001). First shock efficacy was similar among patients with dual and single-coil ICD leads (89.6% vs 92.3%, P = 1.00). When comparing patients with dual versus single-coil ICD leads, there was no difference in the risk of atrial tachyarrhythmias (HR = 1.57, 95% CI: 0.81-3.02, P = 0.18), or in the risk of all-cause mortality (HR = 1.10, 95% CI: 0.58-2.07, P = 0.77). Patients implanted with single- or dual-coil ICD lead had similar short and long-term complication rates (short-term HR = 0.96, 95% CI: 0.56-1.65, P = 0.88, long-term procedure-related HR = 0.99, 95% CI: 0.62-1.59, P = 1.00, long-term ICD lead related: HR = 1.2, 95% CI: 0.5-2.9, P = 0.68) during the mean follow-up of 3.3 years. CONCLUSIONS: Patients with single-coil ICD leads have slightly higher DFTs compared to those with dual-coil leads, but the efficacy, safety, and clinical impact on atrial tachyarrhythmias, and mortality is similar. Implantation of single-coil ICD leads may be favorable in most patients

The inflammatory biomarker YKL-40 decreases stepwise after exercise stress test

BACKGROUND: Serum YKL-40 is an inflammatory biomarker associated with disease activity and mortality in diseases characterized by inflammation such as coronary artery disease (CAD). Exercise has a positive effect on CAD, possibly mediated by a decreased inflammatory activity. This study aimed to compare serial measurements of serum YKL-40 before and after exercise in patients with stable CAD versus controls. MATERIALS AND METHODS: Eleven patients with stable CAD verified by coronary angiography (>70% stenosis) and 11 patients with a computer tomography angiography with no stenosis or calcification (calcium score=0) (controls) performed a standard clinical maximal exercise test. Serum YKL-40 was measured before exercise, immediately after exercise, and every hour for 6 h. RESULTS: Cardiovascular risk factors were more prevalent among the CAD patients compared with the controls. CAD patients had higher serum concentration of YKL-40 at baseline compared with controls, median (interquartile range) 94 (52–151) versus 57 (45–79) μg/l. Serum YKL-40 decreased stepwise after exercise, with a median decrease of 16 (13–39) μg/l for the CAD patients and 13 (10–22) μg/l for the controls from baseline to the lowest value. Thereafter, values increased again toward baseline level. Time after exercise was a significant factor for decrease in serum YKL-40 (P<0.0001), but no difference in YKL-40 decrease over time could be demonstrated between the groups (P=0.12). CONCLUSION: Serum YKL-40 is elevated in patients with documented CAD compared with controls, and it decreases stepwise after exercise in both groups, indicating an anti-inflammatory effect of exercise independent of the presence of coronary atherosclerosis

GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study.

OBJECTIVES: To externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort. DESIGN: Retrospective cohort study. SETTING: Danish nationwide registries. PARTICIPANTS: 90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: External validation was performed using discrimination and calibration plots. C-statistics were compared with CHA2DS2VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes. RESULTS: Of the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66-83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA2DS2VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60). CONCLUSION: In a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA2DS2VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major bleeding

Atrioventricular junction ablation in patients with atrial fibrillation treated with cardiac resynchronization therapy:Positive impact on ventricular arrhythmias, implantable cardioverter-defibrillator therapies and hospitalizations

Aims: We sought to determine whether atrioventricular junction ablation (AVJA) in patients with cardiac resynchronization therapy (CRT) implantable cardioverter-defibrillator (ICD) and with permanent atrial fibrillation (AF) has a positive impact on ICD shocks and hospitalizations compared with rate-slowing drugs. Methods and results: This is a pooled analysis of data from 179 international centres participating in two randomized trials and one prospective observational research. The co-primary endpoints were all-cause ICD shocks and all-cause hospitalizations. Out of 3358 CRT-ICD patients (2720 male, 66.6years), 2694 (80%) were in sinus rhythm (SR) and 664 (20%) had permanent AF-262 (8%) treated with AVJA (AF+AVJA) and 402 (12%) treated with rate-slowing drugs (AF+Drugs). Median follow-up was 18months. The mean (95% confidence intervals) annual rate of all-cause ICD shocks per 100 patient years was 8.0 (5.3-11.9) in AF+AVJA, 43.6 (37.7-50.4) in AF+Drugs, and 34.4 (32.5-36.5) in SR patients, resulting in incidence rate ratio (IRR) reductions of 0.18 (0.10-0.32) for AF+AVJA vs. AF+Drugs (P<0.001) and 0.48 (0.35-0.66) for AF+AVJA vs. SR (P<0.001). These reductions were driven by significant reductions in both appropriate ICD shocks [IRR 0.23 (0.13-0.40), P<0.001, vs. AF+Drugs] and inappropriate ICD shocks [IRR 0.09 (0.04-0.21), P<0.001, vs. AF+Drugs]. Annual rate of all-cause hospitalizations was significantly lower in AF+AVJA vs. AF+Drugs [IRR 0.57 (0.41-0.79), P<0.001] and SR [IRR 0.85 (073-0.98), P=0.027]. Conclusion: In AF patients treated with CRT, AVJA results in a lower incidence and burden of all-cause, appropriate and inappropriate ICD shocks, as well as to fewer all-cause and heart failure hospitalizations