Background Suspected coronary artery disease (CAD) is one of the most common, potentially life-threatening diagnostic problems clinicians encounter. However, no large outcome-based randomized trials ...have been performed to guide the selection of diagnostic strategies for these patients. Methods The PROMISE study is a prospective, randomized trial comparing the effectiveness of 2 initial diagnostic strategies in patients with symptoms suspicious for CAD. Patients are randomized to either (1) functional testing (exercise electrocardiogram, stress nuclear imaging, or stress echocardiogram) or (2) anatomical testing with ≥64-slice multidetector coronary computed tomographic angiography. Tests are interpreted locally in real time by subspecialty certified physicians, and all subsequent care decisions are made by the clinical care team. Sites are provided results of central core laboratory quality and completeness assessment. All subjects are followed up for ≥1 year. The primary end point is the time to occurrence of the composite of death, myocardial infarction, major procedural complications (stroke, major bleeding, anaphylaxis, and renal failure), or hospitalization for unstable angina. Results More than 10,000 symptomatic subjects were randomized in 3.2 years at 193 US and Canadian cardiology, radiology, primary care, urgent care, and anesthesiology sites. Conclusion Multispecialty community practice enrollment into a large pragmatic trial of diagnostic testing strategies is both feasible and efficient. The PROMISE trial will compare the clinical effectiveness of an initial strategy of functional testing against an initial strategy of anatomical testing in symptomatic patients with suspected CAD. Quality of life, resource use, cost-effectiveness, and radiation exposure will be assessed.
Summary Background p38 MAPK inhibition has potential myocardial protective effects. We assessed losmapimod, a potent oral p38 MAPK inhibitor, in patients with non-ST-segment elevation myocardial ...infarction (NSTEMI) in a double-blind, randomised, placebo-controlled trial. Methods From October, 2009, to November, 2011, NSTEMI patients were assigned oral losmapimod (7·5 mg or 15·0 mg loading dose followed by 7·5 mg twice daily) or matching placebo in a 3:3:2 ratio. Safety outcomes were serious adverse events and alanine aminotransferase (ALT) concentrations over 12 weeks, and cardiac events (death, myocardial infarction, recurrent ischaemia, stroke, and heart failure) at 90 days. Efficacy outcomes were high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP) concentrations at 72 h and 12 weeks, and troponin I area under the curve (AUC) over 72 h. The losmapimod groups were pooled for analysis. This trial is registered with ClinicalTrials.gov , number NCT00910962. Findings Of 535 patients enrolled, 526 (98%) received at least one dose of study treatment (losmapimod n=388 and placebo n=138). Safety outcomes did not differ between groups. HsCRP concentrations at 72 h were lower in the losmapimod group than in the placebo group (geometric mean 64·1 nmol/L, 95% CI 53·0–77·6 vs 110·8 nmol/L, 83·1–147·7; p=0·0009) but were similar at 12 weeks. Early geometric mean BNP concentrations were similar at 72 h but significantly lower in the losmapimod group at 12 weeks (37·2 ng/L, 95% CI 32·3–42·9 vs 49·4 ng/L, 38·7–63·0; p=0·04). Mean troponin I AUC values did not differ. Interpretation p38 MAPK inhibition with oral losmapimod was well tolerated in NSTEMI patients and might improve outcomes after acute coronary syndromes. Funding GlaxoSmithKline.
Objectives To compare a steady-state free precession cine sequence–based technique (feature tracking FT) to tagged harmonic phase (HARP) analysis for peak average circumferential myocardial strain ...(εcc ) analysis in a large and heterogeneous population of boys with Duchenne muscular dystrophy (DMD). Background Current εcc assessment techniques require cardiac magnetic resonance–tagged imaging sequences, and their analysis is complex. The FT method can readily be performed on standard cine (steady-state free precession) sequences. Methods We compared mid-left ventricular whole-slice εcc by the 2 techniques in 191 DMD patients grouped according to age and severity of cardiac dysfunction: group B: DMD patients 10 years and younger with normal ejection fraction (EF); group C: DMD patients older than 10 years with normal EF; group D: DMD patients older than 10 years with reduced EF but negative myocardial delayed enhancement (MDE); group E: DMD patients older than 10 years with reduced EF and positive MDE; and group A: 42 control subjects. Retrospective, offline analysis was performed on matched tagged and steady-state free precession slices. Results For the entire study population (N = 233), mean FT εcc values (−13.3 ± 3.8%) were highly correlated with HARP εcc values (−13.6 ± 3.4%), with a Pearson correlation coefficient of 0.899. The mean εcc of DMD patients determined by HARP (−12.52 ± 2.69%) and FT (−12.16 ± 3.12%) was not significantly different (p = NS). Similarly, the mean εcc of the control subjects by determined HARP (−18.85 ± 1.86) and FT (−18.81 ± 1.83) was not significantly different (p = NS). Excellent correlation between the 2 methods was found among subgroups A through E, except there was no significant difference in strain between groups B and C with FT analysis. Conclusions FT-based assessment of εcc correlates highly with εcc derived from tagged images in a large DMD patient population with a wide range of cardiac dysfunction and can be performed without additional imaging.
Background We compared 30-day and 1-year survival among high-risk mitral regurgitation (MR) patients treated with the MitraClip (Abbott Vascular, Abbott Park, IL) with matched non-surgically treated ...patients from the Duke Echocardiography Laboratory Database (DELD). Methods and Results High-risk patients with 3+/4+ MR managed non-surgically between years 2000 and 2010 in the longitudinal DELD were matched to high-risk MitraClip patients. Patient matching was performed using the method of nearest available Mahalanobis distance metric within calipers defined by the propensity score. Kaplan-Meier estimates and stratified Cox proportional hazards models were used to compare survival at 30 days and 1 year. Among 953 high-risk DELD patients available for matching, 30-day and 1-year mortality were 6.5% and 26.2%. Close matches were obtained for 239 of the 351 MitraClip patients. The 30-day mortality in MitraClip patients was lower (4.2%) when compared with matched DELD patients (7.2%). The 1-year relative risk of mortality of the MitraClip compared with non-surgical treatment was 0.64 (95% CI 0.45-0.91; log-rank P = .013). These results in favor of the MitraClip remained significant upon further adjustment for baseline differences between groups ( P = .043). Conclusions This matched comparison of severe MR patients at high surgical risk supports the safety of the MitraClip relative to medical therapy at 30 days and a survival benefit at 1 year.
Objective The present analysis of the Surgical Treatment for Ischemic Heart Failure randomized trial data examined the left ventricular volumes at baseline and 4 months after surgery to determine ...whether any magnitude of postoperative reduction in end-systolic volume affected survival after coronary artery bypass grafting alone compared with bypass grafting plus surgical ventricular reconstruction. Methods Of the 1000 patients randomized, 555 underwent an operation and had a paired imaging assessment with the same modality at baseline and 4 months postoperatively. Of the remaining 455 patients, 424 either died before the 4-month study or did not have paired imaging tests and were excluded, and 21 were not considered because they had died before surgery or did not receive surgery. Results Surgical ventricular reconstruction resulted in improved survival compared with coronary artery bypass grafting alone when the postoperative end-systolic volume index was 70 mL/m2 or less. However, the opposite was true for patients achieving a postoperative volume index greater than 70 mL/m2 . A reduction in the end-systolic volume index of 30% or more compared with baseline was an infrequent event in both treatment groups and did not produce a statistically significant survival benefit with ventricular reconstruction. Conclusions In patients undergoing coronary artery bypass grafting plus surgical ventricular reconstruction, a survival benefit was realized compared with bypass alone, with the achievement of a postoperative end-systolic volume index of 70 mL/m2 or less. Extensive ventricular remodeling at baseline might limit the ability of ventricular reconstruction to achieve a sufficient reduction in volume and clinical benefit.
ST-segment elevation myocardial infarction (STEMI) systems of care have been associated with significant improvement in use and timeliness of reperfusion. Consequently, national guidelines recommend ...that each community should develop a regional STEMI care system. However, significant barriers continue to impede widespread establishment of regional STEMI care systems in the United States. We designed the Regional Systems of Care Demonstration Project: Mission: Lifeline STEMI Systems Accelerator, a national educational outcome research study in collaboration with the American Heart Association, to comprehensively accelerate the implementation of STEMI care systems in 17 major metropolitan regions encompassing >1,500 emergency medical service agencies and 450 hospitals across the United States. The goals of the program are to identify regional gaps, barriers, and inefficiencies in STEMI care and to devise strategies to implement proven recommendations to enhance the quality and consistency of care. The study interventions, facilitated by national faculty with expertise in regional STEMI system organization in partnership with American Heart Association representatives, draw upon specific resources with proven past effectiveness in augmenting regional organization. These include bringing together leading regional health care providers and institutions to establish common commitment to STEMI care improvement, developing consensus-based standardized protocols in accordance with national professional guidelines to address local needs, and collecting and regularly reviewing regional data to identify areas for improvement. Interventions focus on each component of the reperfusion process: the emergency medical service, the emergency department, the catheterization laboratory, and inter-hospital transfer. The impact of regionalization of STEMI care on clinical outcomes will be evaluated.
Abstract Atrial fibrillation (AF) is common, increasing as the population ages, and a major cause of embolic stroke. While oral anticoagulation (OAC) is highly effective at preventing stroke in ...patients with AF, it continues to be underused in eligible patients worldwide. The objective of this prospective, cluster randomized controlled trial (IMPACT-AF; ClinicalTrials.gov #NCT02082548) is to determine whether a comprehensive customized intervention will increase the rate and persistence of use of OAC in patients with AF. IMPACT-AF will be conducted in approximately 50 centers in 5 low- to middle-income countries. Before randomization, sites within countries will be paired to match in size, practice type and baseline rate of OAC use. Site pairs will be randomized to intervention versus control. In total, 40 to 70 patients with AF and at least 2 CHA2 DS2 -VASc risk factors will be enrolled at each site using a consecutive enrollment strategy, with the goal of capturing actual practice patterns. We aim for patients with a new diagnosis of AF to comprise at least 30% of the study cohort. Assuming an average baseline OAC use of 60% and a post-intervention use of 70% with a post-control rate of 60%, there will be roughly 94-98% power with 25 clusters per group (intracluster correlation coefficient of 0.02). While this trial focuses on improving treatment use and reducing preventable strokes, we aim to better understand the reasons for OAC underuse. This will improve the intervention with the goal of creating educational recommendations to improve care for patients with AF.
Abstract Background Patients with left ventricular (LV) systolic dysfunction, coronary artery disease (CAD), and angina are often thought to have a worse prognosis and a greater prognostic benefit ...from coronary artery bypass graft (CABG) surgery than those without angina. Objectives This study investigated: 1) whether angina was associated with a worse prognosis; 2) whether angina identified patients who had a greater survival benefit from CABG; and 3) whether CABG improved angina in patients with LV systolic dysfunction and CAD. Methods We performed an analysis of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, in which 1,212 patients with an ejection fraction ≤35% and CAD were randomized to CABG or medical therapy. Multivariable Cox and logistic models were used to assess long-term clinical outcomes. Results At baseline, 770 patients (64%) reported angina. Among patients assigned to medical therapy, all-cause mortality was similar in patients with and without angina (hazard ratio HR: 1.05; 95% confidence interval CI: 0.79 to 1.38). The effect of CABG was similar whether the patient had angina (HR: 0.89; 95% CI: 0.71 to 1.13) or not (HR: 0.68; 95% CI: 0.50 to 0.94; p interaction = 0.14). Patients assigned to CABG were more likely to report improvement in angina than those assigned to medical therapy alone (odds ratio: 0.70; 95% CI: 0.55 to 0.90; p < 0.01). Conclusions Angina does not predict all-cause mortality in medically treated patients with LV systolic dysfunction and CAD, nor does it identify patients who have a greater survival benefit from CABG. However, CABG does improve angina to a greater extent than medical therapy alone. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease STICH; NCT00023595 )
Abstract Objectives The purpose of this study was to assess the benefit of primary prevention implantable cardioverter defibrillators (ICDs) in women. Background Clinical trials of primary prevention ...ICDs enrolled a limited number of women. Methods Using a propensity score method, we matched 490 women ≥65 years of age who received an ICD during a hospitalization for heart failure in the National Cardiovascular Data Registry ICD Registry from January 1, 2006, through December 31, 2007, to 490 ICD-eligible women without an ICD hospitalized for heart failure in the Get With The Guidelines for Heart Failure database from January 1, 2006, through December 31, 2009. The primary endpoint was all-cause mortality obtained from the Medicare Claims Database. An identical analysis was conducted in men. Results Median follow-up for patients with an ICD was 4.6 years versus 3.2 years for patients with no ICD. Compared with women with no ICD, those with an ICD were younger and less frequently white. In the matched cohorts, the survival of women with an ICD was significantly longer than that of women without an ICD (adjusted hazard ratio: 0.79, 95% confidence interval: 0.66 to 0.95; p = 0.013). Similarly, men with an ICD had longer survival than men without an ICD (adjusted hazard ratio: 0.73, 95% confidence interval: 0.65 to 0.83; p < 0.0001). There was no interaction between sex and the presence of an ICD with respect to survival (p = 0.44). Conclusions Among older women with left ventricular dysfunction, a primary prevention ICD was associated with a significant survival benefit that was nearly identical to that seen in men. These findings support the use of primary prevention ICDs in eligible patients regardless of sex.
Azimilide Reduces Emergency Department Visits and Hospitalizations in Patients With an Implantable Cardioverter-Defibrillator in a Placebo-Controlled Clinical Trial Paul Dorian, Hussein R. ...Al-Khalidi, Stefan H. Hohnloser,Jose M. Brum, Preston M. Dunnmon, Craig M. Pratt, Michael J. Holroyde, Peter Kowey, on behalf of the SHIELD (SHock Inhibition Evaluation with AzimiLiDe) Investigators A total of 633 patients were randomized in the SHIELD (SHock Inhibition Evaluation with AzimiLiDe) trial, and, prospectively, cardiac emergency department (ED) visit and hospitalization data were collected over 1 year. Baseline characteristics among groups were no different. One hundred ten of 214 patients on placebo and 77 of 220 patients on 75-mg azimilide (p < 0.001) experienced at least 1 cardiac ED visit and hospitalization. Only the presence of congestive heart failure (New York Heart Association functional class II/III) was an independent clinical predictor of cardiac ED visits and hospitalizations. Azimilide significantly reduces the proportion of patients and the number of episodes of symptomatic arrhythmias treated by antitachycardia pacing or shock therapy and the number of ED visits and hospitalizations.
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