Cardiovascular magnetic resonance-GUIDEd management of mild to moderate left ventricular systolic dysfunction (CMR GUIDE): Study protocol for a randomized controlled trial.

BACKGROUND: The majority of sudden cardiac death (SCD) in patients with heart failure occurs in those with mild-moderate left ventricular (LV) systolic dysfunction (LVEF 36-50%) who under current guidelines are ineligible for primary prevention implantable cardiac defibrillator (ICD) therapy. Recent data suggest that cardiac magnetic resonance (CMR) evidence of replacement fibrosis forms a substrate for malignant arrhythmia and therefore potentially identifies a subgroup at increased risk of SCD. Our hypothesis is that among patients with mild-moderate LV systolic dysfunction, a CMR-guided management strategy for ICD insertion based on the presence of scar or fibrosis is superior to a current strategy of standard care. METHODS/DESIGN: CMR GUIDE is a prospective, multicenter randomized control trial enrolling patients with mild-moderate LV systolic dysfunction and CMR evidence of fibrosis on optimal heart failure therapy. Participants will be randomized to receive either a primary prevention ICD or an implantable loop recorder (ILR). The primary endpoint is the time to SCD or hemodynamically significant ventricular arrhythmia (VF or VT) during an average 4-year follow-up. Secondary endpoints include quality of life assessed by Minnesota Living with Heart Failure Questionnaire, heart failure related hospitalizations, and a cost-utility analysis. Clinical trials.gov identifier NCT01918215. DISCUSSION: CMR GUIDE trial will add substantially to our understanding of the role of myocardial fibrosis and the risk of developing life-threatening ventricular arrhythmias. If the superiority of a CMR-guided approach over standard care is proven, it may change international clinical guidelines, with the potential to considerably increase survival in this growing patient population.

The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis.

AIMS: Thromboembolic risk stratification schemes and clinical guidelines for atrial fibrillation (AF) regard risk as independent of classification into paroxysmal (PAF) and non-paroxysmal atrial fibrillation (NPAF). The aim of the current study was to conduct a systematic review evaluating the impact of AF type on thromboembolism, bleeding, and mortality. METHODS AND RESULTS: PubMed was searched through 27 November 2014 for randomized controlled trials, cohort studies, and case series reporting prospectively collected clinical outcomes stratified by AF type. The incidence of thromboembolism, mortality, and bleeding was extracted. Atrial fibrillation clinical outcome data were extracted from 12 studies containing 99 996 patients. The unadjusted risk ratio (RR) for thromboembolism in NPAF vs. PAF was 1.355 (95% CI: 1.169-1.571, P < 0.001). In the study subset off oral anticoagulation, unadjusted RR was 1.689 (95% CI: 1.151-2.480, P = 0.007). The overall multivariable adjusted hazard ratio (HR) for thromboembolism was 1.384 (95% CI: 1.191-1.608, P < 0.001). The overall unadjusted RR for all-cause mortality was 1.462 (95% CI: 1.255-1.703, P < 0.001). Multivariable adjusted HR for all-cause mortality was 1.217 (95% CI: 1.085-1.365, P < 0.001). Rates of bleeding were similar, with unadjusted RR 1.00 (95% CI: 0.919-1.087, P = 0.994) and adjusted HR 1.025 (95% CI: 0.898-1.170, P = 0.715). CONCLUSION: Non-paroxysmal atrial fibrillation is associated with a highly significant increase in thromboembolism and death. These data suggest the need for new therapies to prevent AF progression and further studies to explore the integration of AF type into models of thromboembolic risk.

P2Y12 Inhibitor Pre-Treatment in Non-ST-Elevation Acute Coronary Syndrome: A Decision-Analytic Model.

Current guidelines recommend initiation of a P2Y12 inhibitor for all patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) at the time of diagnosis (pre-treatment); however, there are no randomized trials directly comparing pre-treatment with initiation at the time of angiography to support this practice. We explore clinical and institutional parameters potentially associated with benefit with this strategy in a decision-analytic model based on available evidence from randomised trials. A decision analysis model was constructed comparing three P2Y12 inhibitors in addition to aspirin in patients with NSTE-ACS. Based on clinical trial data, the cumulative probability of 30 day mortality, myocardial infarction (MI) and major bleeding were determined, and used to calculate the net clinical benefit (NCB) with and without pre-treatment. Sensitivity analysis was performed to assess the relationship between NCB and baseline ischemic risk, bleeding risk, time to angiography and local surgical revascularization rates. Pre-treatment with ticagrelor and clopidogrel was associated with a greater than 50% likelihood of providing a >1% increase in 30 day NCB when baseline estimated ischemic risk exceeds 11% and 14%, respectively. Prasugrel pre-treatment did not achieve a greater than 50% probability of an increase in NCB regardless of baseline ischemic risk. Institutional surgical revascularization rates and time to coronary angiography did not correlate with the likelihood of benefit from P2Y12 pre-treatment. In conclusion, pre-treatment with P2Y12 inhibition is unlikely to be beneficial to the majority of patients presenting with NSTE-ACS. A tailored assessment of each patient's individual ischemic and bleeding risk may identify those likely to benefit.