255 CARDIAC MRI: DETECTION OF MI IN ISCHEMIC, NONISCHEMIC, AND MIXED CARDIOMYOPATHY

IntroductionCardiomyopathies are classified as ischemic (ICM) based on the following clinical criteria: evidence of prior MI, significant coronary stenosis on coronary angiography, and/or prior revascularization. Patients who do not meet these criteria are classified as nonischemic (NICM).PurposeThis study investigated the use of Cardiac MRI (CMRI) to identify evidence of prior MI in patients with severe left ventricular dysfunction of mixed etiologies.MethodsCMRI was performed on 128 patients with severe left ventricular dysfunction. 100 (78%) patients were classified as ICM (mean EF: 29±10%) and 28 (22%) as NICM (mean EF: 31±11%). Two blinded observers evaluated each study.Results95 patients (95%) with clinical criteria for ICM demonstrated MI, despite the fact that 32 (32%) of the ICM patients had no history or clinical evidence of prior MI. In contrast 6/28 patients (21%) with NICM demonstrated MI. The mean infarct size as percent of LV mass was 27±18 and 17±13 among ICM and NICM patients, respectively (p=0.12); transmural MI was seen in 57% of ICM patients whereas only 14% of NICM patients had evidence of transmural hyperenhancement (p≤0.001). Table shows the relationship between the extent of CAD based on angiography and the presence or absence of infarct detected by CMRI. 12 patients with ICM were identified with LV dysfunction out of proportion to the extent of CAD. 10 of the 12 patients (83%) had evidence on CMRI of prior MI but had no such history. The mean infarct size was 15±13% of LV mass. ConclusionsIn heart failure patients, 95% of patients with severe left ventricular dysfunction satisfying clinical criteria for ICM have evidence of prior MI as identified by contrast-enhanced MRI, with 32% of these patients lacking a history or clinical evidence of prior MI (silent MI). 21% of patients with non-ischemic cardiomyopathy have MRI evidence of prior MI

253 CARDIAC MRI: INFARCT SIZE IS AN INDEPENDENT PREDICTOR OF MORTALITY IN PATIENTS WITH CORONARY ARTERY DISEASE

BackgroundCardiac magnetic resonance imaging (CMRI) can accurately determine infarct size. Prior studies using indirect methods to assess infarct size have shown that patients with larger myocardial infarctions (MI) have a worse prognosis than those with a smaller MI. This study assessed the prognostic significance of infarct size by CMRI.MethodsCine and contrast MRI were performed in patients with coronary artery disease (CAD) undergoing routine cardiac evaluation.Results100 patients (mean age 66±11 years, 87% male, diabetes 23%, hypertension 49%, prior MI 62%, mean ejection fraction (EF) 34±13%) underwent CMRI. Mean follow-up was 25±18 months after MRI, during which time 15 patients died. Cox regression was used to estimate risk of death associated with traditional risk factors, heart failure symptoms, EF, angiographic severity of CAD, and extent of infarct size. Evidence of MI based on CMRI was present in 91% of patients. The only two significant univariate predictors of death (all-cause) were evidence of myocardial infarction greater than 15% of left ventricular (LV) mass, and extent of LV dysfunction based on EF (p≤0.05). On multivariate analysis, the presence of MI ≥15% of LV mass was the single best independent predictor of death (p=0.01) with an adjusted relative risk of 9.9 (95% CI 1.6-63), figure 1.ConclusionsThe extent of myocardial infarction determined by CMRI is an independent predictor of death in patients with CAD

254 CARDIAC MRI: COMPARISON OF INFARCT SIZE BY QUANTITATIVE PLANIMETRY VERSUS A QUALITATIVE VISUAL SCORING METHOD

BackgroundAccurate evaluation of infarct size by cardiac magnetic resonance (CMR) has important clinical significance. We examined how well a qualitative visual method of scoring (VS) the extent of myocardial infarction correlates with a quantitative planimetry (PL) method of determining the extent of left ventricular (LV) infarct size.Methods51 consecutive patients with evidence of myocardial infarction by CMR were evaluated. Two different methods were used to calculate infarct mass as percentage of LV mass. A quantitative method, planimetry, was performed using an NIH software algorithm in which infarct mass was calculated based on a manual drawing of infarcted regions. In a second approach, a qualitative visualization scoring of infarcted regions was performed based on a segmental model in which each short axis slice was evenly divided into 12 segments. Transmural extent of hyperenhancement (HE) was then graded on a 4-point scale: 0, 0% HE; 1, 1-25% HE; 2, 26-50% HE; 3, 51-75% HE; 4, 76-100% HE. The final score of each patient (sum of areas of HE) was divided by the total possible score, yielding the infarct size as a percentage of LV mass.ResultsThe mean LV ejection fraction was 34±16%; the mean infarct size as a percentage of LV mass was 20±12 by planimetry, and 25±12 by VS (p: NS). The correlation coefficient between the two different modalities was 0.84.ConclusionThis study showed a good correlation between a qualitative and quantitative method of determining infarct size

Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial.

Importance In phase 2 studies, evolocumab, a fully human monoclonal antibody to PCSK9, reduced LDL-C levels in patients receiving statin therapy. Objective To evaluate the efficacy and tolerability of evolocumab when used in combination with a moderate- vs high-intensity statin. Design, Setting, and Patients Phase 3, 12-week, randomized, double-blind, placebo- and ezetimibe-controlled study conducted between January and December of 2013 in patients with primary hypercholesterolemia and mixed dyslipidemia at 198 sites in 17 countries. Interventions Patients (n = 2067) were randomized to 1 of 24 treatment groups in 2 steps. Patients were initially randomized to a daily, moderate-intensity (atorvastatin [10 mg], simvastatin [40 mg], or rosuvastatin [5 mg]) or high-intensity (atorvastatin [80 mg], rosuvastatin [40 mg]) statin. After a 4-week lipid-stabilization period, patients (n = 1899) were randomized to compare evolocumab (140 mg every 2 weeks or 420 mg monthly) with placebo (every 2 weeks or monthly) or ezetimibe (10 mg or placebo daily; atorvastatin patients only) when added to statin therapies. Main Outcomes and Measures Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) level at the mean of weeks 10 and 12 and at week 12. Results Evolocumab reduced LDL-C levels by 66% (95% CI, 58% to 73%) to 75% (95% CI, 65% to 84%) (every 2 weeks) and by 63% (95% CI, 54% to 71%) to 75% (95% CI, 67% to 83%) (monthly) vs placebo at the mean of weeks 10 and 12 in the moderate- and high-intensity statin-treated groups; the LDL-C reductions at week 12 were comparable. For moderate-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 115 to 124 mg/dL to an on-treatment mean of 39 to 49 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 123 to 126 mg/dL to an on-treatment mean of 43 to 48 mg/dL. For high-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 35 to 38 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 33 to 35 mg/dL. Adverse events were reported in 36%, 40%, and 39% of evolocumab-, ezetimibe-, and placebo-treated patients, respectively. The most common adverse events in evolocumab-treated patients were back pain, arthralgia, headache, muscle spasms, and pain in extremity (all <2%). Conclusions and Relevance In this 12-week trial conducted among patients with primary hypercholesterolemia and mixed dyslipidemia, evolocumab added to moderate- or high-intensity statin therapy resulted in additional LDL-C lowering. Further studies are needed to evaluate the longer-term clinical outcomes and safety of this approach for LDL-C lowering. Trial Registration clinicaltrials.gov Identifier: NCT0176386

Evolocumab and clinical outcomes in patients with cardiovascular disease

peer reviewedBACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets. © 2017 Massachusetts Medical Society

Evolocumab and clinical outcomes in patients with cardiovascular disease

BACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets

Edoxaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)