Variability in Ejection Fraction Measured By Echocardiography, Gated Single-Photon Emission Computed Tomography, and Cardiac Magnetic Resonance in Patients With Coronary Artery Disease and Left Ventricular Dysfunction

Importance: Clinical decisions are frequently based on measurement of left ventricular ejection fraction (LVEF). Limited information exists regarding inconsistencies in LVEF measurements when determined by various imaging modalities and the potential impact of such variability. Objective: To determine the intermodality variability of LVEF measured by echocardiography, gated single-photon emission computed tomography (SPECT), and cardiovascular magnetic resonance (CMR) in patients with left ventricular dysfunction. Design, Setting, and Participants: International multicenter diagnostic study with LVEF imaging performed at 127 clinical sites in 26 countries from July 24, 2002, to May 5, 2007, and measured by core laboratories. Secondary study of clinical diagnostic measurements of LVEF in the Surgical Treatment for Ischemic Heart Failure (STICH), a randomized trial to identify the optimal treatment strategy for patients with LVEF of 35% or less and coronary artery disease. Data analysis was conducted from March 19, 2016, to May 29, 2018. Main Outcomes and Measures: At baseline, most patients had an echocardiogram and subsets of patients underwent SPECT and/or CMR. Left ventricular ejection fraction was measured by a core laboratory for each modality independent of the results of other modalities, and measurements were compared among imaging methods using correlation, Bland-Altman plots, and coverage probability methods. Association of LVEF by each method and death was assessed. Results: A total of 2032 patients (mean [SD] age, 60.9 [9.6] years; 1759 [86.6%] male) with baseline LVEF data were included. Correlation of LVEF between modalities was r = 0.601 (for biplane echocardiography and SPECT [n = 385]), r = 0.493 (for biplane echocardiography and CMR [n = 204]), and r = 0.660 (for CMR and SPECT [n = 134]). Bland-Altman plots showed only moderate agreement in LVEF measurements from all 3 core laboratories with no substantial overestimation or underestimation of LVEF by any modality. The percentage of observations that fell within a range of 5% ranged from 43% to 54% between different imaging modalities. Conclusions and Relevance: In this international multicenter study of patients with coronary artery disease and reduced LVEF, there was substantial variation between modalities in LVEF determination by core laboratories. This variability should be considered in clinical management and trial design. Trial Registration: Clinicaltrials.gov Identifier: NCT00023595

Coronary-artery bypass surgery in patients with ischemic cardiomyopathy

BACKGROUND The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear. METHODS From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years. RESULTS A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test). CONCLUSIONS In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of Health; STICH [and STICHES] ClinicalTrials.gov number, NCT00023595.

Sudden cardiac death in patients with ischemic heart failure undergoing coronary artery bypass grafting results from the STICH randomized clinical trial (Surgical Treatment for Ischemic Heart Failure)

Background—The risk of sudden cardiac death (SCD) in patients with heart failure following CABG has not been examined in a contemporary clinical trial of surgical revascularization. This analysis describes the incidence, timing and clinical predictors of SCD after CABG. Methods—Patients enrolled in the Surgical Treatment of Ischemic Heart Failure (STICH) trial who underwent CABG with or without surgical ventricular reconstruction (SVR) were included. We excluded patients with prior ICD and those randomized only to medical therapy. The primary outcome was SCD as adjudicated by a blinded committee. A Cox model was used to examine and identify predictors of SCD. The Fine and Gray method was used to estimate the incidence of SCD accounting for the competing risk of other deaths. Results—Over a median follow-up of 46 months, 113 patients of 1411 patients who received CABG without (n = 934) or with SVR (n = 477) had SCD; 311 died of other causes. The mean LVEF at enrollment was 28±9%. The 5-year cumulative incidence of SCD was 8.5%. Patients who had SCD and those who did not die were younger and had fewer comorbid conditions than those who died for reasons other than SCD. In the first 30 days after CABG, SCD (n=5) accounted for 7% of all deaths. The numerically greatest monthly rate of SCD was in the 31-90 day time period. In a multivariable analysis including baseline demographics, risk factors, coronary anatomy and LV function, ESVI and BNP were most strongly associated with SCD. Conclusions—The monthly risk of SCD shortly after CABG among patients with a low LVEF is highest between the first and third month, suggesting that risk stratification for SCD should occur early in the postoperative period, particularly in patients with increased preoperative ESVI and/or BNP

Severity of Remodeling, Myocardial Viability, and Survival in Ischemic LV Dysfunction After Surgical Revascularization

AbstractObjectivesThis study sought to test the hypothesis that end-systolic volume (ESV), as a marker of severity of left ventricular (LV) remodeling, influences the relationship between myocardial viability and survival in patients with coronary artery disease and LV systolic dysfunction.BackgroundRetrospective studies of ischemic LV dysfunction suggest that the severity of LV remodeling determines whether myocardial viability predicts improved survival with surgical compared with medical therapy, with coronary artery bypass grafting (CABG) only benefitting patients with viable myocardium who have smaller ESV. However, this has not been tested prospectively.MethodsInteractions of end-systolic volume index (ESVI), myocardial viability, and treatment with respect to survival were assessed in patients in the prospective randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial of CABG versus medical therapy who underwent viability assessment (n = 601; age 61 ± 9 years; ejection fraction ≤35%), with a median follow-up of 5.1 years. Median ESVI was 84 ml/m2. Viability was assessed by single-photon emission computed tomography or dobutamine echocardiography using pre-specified criteria.ResultsMortality was highest among patients with larger ESVI and nonviability (p < 0.001), but no interaction was observed between ESVI, viability status, and treatment assignment (p = 0.491). Specifically, the effect of CABG versus medical therapy in patients with viable myocardium and ESVI ≤84 ml/m2 (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.56 to 1.29) was no different than in patients with viability and ESVI >84 ml/m2 (HR: 0.87; 95% CI: 0.57 to 1.31). Other ESVI thresholds yielded similar results, including ESVI ≤60 ml/m2 (HR: 0.87; 95% CI: 0.44 to 1.74). ESVI and viability assessed as continuous rather than dichotomous variables yielded similar results (p = 0.562).ConclusionsAmong patients with ischemic cardiomyopathy, those with greater LV ESVI and no substantial viability had worse prognosis. However, the effect of CABG relative to medical therapy was not differentially influenced by the combination of these 2 factors. Lower ESVI did not identify patients in whom myocardial viability predicted better outcome with CABG relative to medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595

Sudden Cardiac Death in Patients With Ischemic Heart Failure Undergoing Coronary Artery Bypass Grafting: Results From the STICH Randomized Clinical Trial (Surgical Treatment for Ischemic Heart Failure).

BACKGROUND: The risk of sudden cardiac death (SCD) in patients with heart failure after coronary artery bypass graft surgery (CABG) has not been examined in a contemporary clinical trial of surgical revascularization. This analysis describes the incidence, timing, and clinical predictors of SCD after CABG. METHODS: Patients enrolled in the STICH trial (Surgical Treatment of Ischemic Heart Failure) who underwent CABG with or without surgical ventricular reconstruction were included. We excluded patients with prior implantable cardioverter-defibrillator and those randomized only to medical therapy. The primary outcome was SCD as adjudicated by a blinded committee. A Cox model was used to examine and identify predictors of SCD. The Fine and Gray method was used to estimate the incidence of SCD accounting for the competing risk of other deaths. RESULTS: Over a median follow-up of 46 months, 113 of 1411 patients who received CABG without (n = 934) or with (n = 477) surgical ventricular reconstruction had SCD; 311 died of other causes. The mean left ventricular ejection fraction at enrollment was 28±9%. The 5-year cumulative incidence of SCD was 8.5%. Patients who had SCD and those who did not die were younger and had fewer comorbid conditions than did those who died of causes other than SCD. In the first 30 days after CABG, SCD (n=5) accounted for 7% of all deaths. The numerically greatest monthly rate of SCD was in the 31- to 90-day time period. In a multivariable analysis including baseline demographics, risk factors, coronary anatomy, and left ventricular function, end-systolic volume index and B-type natriuretic peptide were most strongly associated with SCD. CONCLUSIONS: The monthly risk of SCD shortly after CABG among patients with a low left ventricular ejection fraction is highest between the first and third months, suggesting that risk stratification for SCD should occur early in the postoperative period, particularly in patients with increased preoperative end-systolic volume index or B-type natriuretic peptide. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT0002359

Myocardial viability and survival in ischemic left ventricular dysfunction

BACKGROUND The assessment of myocardial viability has been used to identify patients with coronary artery disease and left ventricular dysfunction in whom coronary-artery bypass grafting (CABG) will provide a survival benefit. However, the efficacy of this approach is uncertain. METHODS In a substudy of patients with coronary artery disease and left ventricular dysfunction who were enrolled in a randomized trial of medical therapy with or without CABG, we used single-photon-emission computed tomography (SPECT), dobutamine echocardiography, or both to assess myocardial viability on the basis of pre-specified thresholds. RESULTS Among the 1212 patients enrolled in the randomized trial, 601 underwent assessment of myocardial viability. Of these patients, we randomly assigned 298 to receive medical therapy plus CABG and 303 to receive medical therapy alone. A total of 178 of 487 patients with viable myocardium (37%) and 58 of 114 patients without viable myocardium (51%) died (hazard ratio for death among patients with viable myocardium, 0.64; 95% confidence interval [CI], 0.48 to 0.86; P = 0.003). However, after adjustment for other baseline variables, this association with mortality was not significant (P = 0.21). There was no significant interaction between viability status and treatment assignment with respect to mortality (P = 0.53). CONCLUSIONS The presence of viable myocardium was associated with a greater likelihood of survival in patients with coronary artery disease and left ventricular dysfunction, but this relationship was not significant after adjustment for other baseline variables. The assessment of myocardial viability did not identify patients with a differential survival benefit from CABG, as compared with medical therapy alone.National Heart, Lung, and Blood Institute (NHLBI/NIH)[U01-HL-069009]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069010]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069011]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069012]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069012-03]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069013]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069015]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-070011]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-072683]SorinAstellas HealthcareBraccoLantheus Medical ImagingMitralignRegeneRxNovartisGileadBoehringer Ingelheim Pharmaceutical

The Association Between Blood Pressure and Long-Term Outcomes of Patients With Ischaemic Cardiomyopathy With and Without Surgical Revascularization: An Analysis of the STICH Trial

Aims: Hypertension (HTN) is a well-known contributor to cardiovascular disease, including heart failure (HF) and coronary artery disease, and is the leading risk factor for premature death world-wide. A J- or U-shaped relationship has been suggested between blood pressure (BP) and clinical outcomes in different studies. However, there is little information about the significance of BP on the outcomes of patients with coronary artery disease and left ventricular dysfunction. This study aimed to determine the relationship between BP and mortality outcomes in patients with ischaemic cardiomyopathy. Methods and results: The influence of BP during a median follow-up of 9.8 years was studied in a total of 1212 patients with ejection fractio

Inducible Myocardial Ischemia and Outcomes in Patients With Coronary Artery Disease and Left Ventricular Dysfunction.

ObjectivesThe study objectives were to test the hypotheses that ischemia during stress testing has prognostic value and identifies those patients with coronary artery disease (CAD) with left ventricular (LV) dysfunction who derive the greatest benefit from coronary artery bypass grafting (CABG) compared with medical therapy.BackgroundThe clinical significance of stress-induced ischemia in patients with CAD and moderately to severely reduced LV ejection fraction (EF) is largely unknown.MethodsThe STICH (Surgical Treatment for IsChemic Heart Failure) trial randomized patients with CAD and EF ≤35% to CABG or medical therapy. In the current study, we assessed the outcomes of those STICH patients who underwent a radionuclide (RN) stress test or a dobutamine stress echocardiogram (DSE). A test was considered positive for ischemia by RN testing if the summed difference score (difference in tracer activity between stress and rest) was ≥4 or if ≥2 of 16 segments were ischemic during DSE. Clinical endpoints were assessed by intention to treat during a median follow-up of 56 months.ResultsOf the 399 study patients (51 women, mean EF 26 ± 8%), 197 were randomized to CABG and 202 were randomized to medical therapy. Myocardial ischemia was induced during stress testing in 256 patients (64% of the study population). Patients with and without ischemia were similar in age, multivessel CAD, previous myocardial infarction, LV EF, LV volumes, and treatment allocation (all p = NS). There was no difference between patients with and without ischemia in all-cause mortality (hazard ratio: 1.08; 95% confidence interval: 0.77 to 1.50; p = 0.66), cardiovascular mortality, or all-cause mortality plus cardiovascular hospitalization. There was no interaction between ischemia and treatment for any clinical endpoint.ConclusionsIn CAD with severe LV dysfunction, inducible myocardial ischemia does not identify patients with worse prognosis or those with greater benefit from CABG over optimal medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595

Implication of right ventricular dysfunction on long-term outcome in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting with or without surgical ventricular reconstruction

Objective: Whether right ventricular dysfunction affects clinical outcome after coronary artery bypass grafting with or without surgical ventricular reconstruction is still unknown. The aim of the study was to assess the impact of right ventricular dysfunction on clinical outcome in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting with or without surgical ventricular reconstruction. Methods: Of 1000 patients in the Surgical Treatment for Ischemic Heart Failure with coronary artery disease, left ventricular ejection fraction 35% or less, and anterior dysfunction, who were randomized to undergo coronary artery bypass grafting or coronary artery bypass grafting + surgical ventricular reconstruction, baseline right ventricular function could be assessed by echocardiography in 866 patients. Patients were followed for a median of 48 months. All-cause mortality or cardiovascular hospitalization was the primary end point, and all-cause mortality alone was a secondary end point. Results: Right ventricular dysfunction was mild in 102 patients (12%) and moderate or severe in 78 patients (9%). Moderate to severe right ventricular dysfunction was associated with a larger left ventricle, lower ejection fraction, more severe mitral regurgitation, higher filling pressure, and higher pulmonary artery systolic pressure (all P &#60; .0001) compared with normal or mildly reduced right ventricular function. A significant interaction between right ventricular dysfunction and treatment allocation was observed. Patients with moderate or severe right ventricular dysfunction who received coronary artery bypass grafting + surgical ventricular reconstruction had significantly worse outcomes compared with patients who received coronary artery bypass grafting alone on both the primary (hazard ratio, 1.86; confidence interval, 1.06-3.26; P = .028) and the secondary (hazard ratio, 3.37; confidence interval, 1.36-8.37; P = .005) end points. After adjusting for all other prognostic clinical factors, the interaction remained significant with respect to all-cause mortality (P = .022). Conclusions: Adding surgical ventricular reconstruction to coronary artery bypass grafting may worsen long-term survival in patients with ischemic cardiomyopathy with moderate to severe right ventricular dysfunction, which reflects advanced left ventricular remodeling