Viability and Outcomes With Revascularization or Medical Therapy in Ischemic Ventricular Dysfunction: A Prespecified Secondary Analysis of the REVIVED-BCIS2 Trial.

IMPORTANCE: In the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, percutaneous coronary intervention (PCI) did not improve outcomes for patients with ischemic left ventricular dysfunction. Whether myocardial viability testing had prognostic utility for these patients or identified a subpopulation who may benefit from PCI remained unclear. OBJECTIVE: To determine the effect of the extent of viable and nonviable myocardium on the effectiveness of PCI, prognosis, and improvement in left ventricular function. DESIGN, SETTING, AND PARTICIPANTS: Prospective open-label randomized clinical trial recruiting between August 28, 2013, and March 19, 2020, with a median follow-up of 3.4 years (IQR, 2.3-5.0 years). A total of 40 secondary and tertiary care centers in the United Kingdom were included. Of 700 randomly assigned patients, 610 with left ventricular ejection fraction less than or equal to 35%, extensive coronary artery disease, and evidence of viability in at least 4 myocardial segments that were dysfunctional at rest and who underwent blinded core laboratory viability characterization were included. Data analysis was conducted from March 31, 2022, to May 1, 2023. INTERVENTION: Percutaneous coronary intervention in addition to optimal medical therapy. MAIN OUTCOMES AND MEASURES: Blinded core laboratory analysis was performed of cardiac magnetic resonance imaging scans and dobutamine stress echocardiograms to quantify the extent of viable and nonviable myocardium, expressed as an absolute percentage of left ventricular mass. The primary outcome of this subgroup analysis was the composite of all-cause death or hospitalization for heart failure. Secondary outcomes were all-cause death, cardiovascular death, hospitalization for heart failure, and improved left ventricular function at 6 months. RESULTS: The mean (SD) age of the participants was 69.3 (9.0) years. In the PCI group, 258 (87%) were male, and in the optimal medical therapy group, 277 (88%) were male. The primary outcome occurred in 107 of 295 participants assigned to PCI and 114 of 315 participants assigned to optimal medical therapy alone. There was no interaction between the extent of viable or nonviable myocardium and the effect of PCI on the primary or any secondary outcome. Across the study population, the extent of viable myocardium was not associated with the primary outcome (hazard ratio per 10% increase, 0.98; 95% CI, 0.93-1.04) or any secondary outcome. The extent of nonviable myocardium was associated with the primary outcome (hazard ratio, 1.07; 95% CI, 1.00-1.15), all-cause death, cardiovascular death, and improvement in left ventricular function. CONCLUSIONS AND RELEVANCE: This study found that viability testing does not identify patients with ischemic cardiomyopathy who benefit from PCI. The extent of nonviable myocardium, but not the extent of viable myocardium, is associated with event-free survival and likelihood of improvement of left ventricular function. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01920048

Imaging Biomarkers of Subclinical Cardiovascular Disease in Asymptomatic European Whites and Indian Asians: A Population Study

Background: Subclinical biomarkers of cardiovascular disease (CVD) are being increasingly applied in clinical settings to refine cardiovascular risk stratification and also as an epidemiological tool to enhance the understanding of disease mechanisms. Indian Asians living in the United Kingdom have at least a 50% higher risk of CVD mortality compared to European whites. The excess mortality risk cannot be explained by the pattern of classical risk factors which are generally lower in Indian Asians, and there are no tools that identify their elevated CVD risk. Objectives: To explore potential CVD mechanisms using established and novel imaging biomarkers of subclinical atherosclerosis and left ventricular (LV) function, in a large bi-ethnic cohort of asymptomatic European white and Indian Asian subjects. Mechanisms potentially responsible for the excess CVD mortality observed in UK Indian Asians will also be examined. Methods: A total of 2,439 subjects were recruited from the LOLIPOP study, of which 2,288 were free from clinical CVD. All subjects underwent carotid ultrasonography and echocardiography with tissue Doppler imaging for estimation of LV filling pressure (E/Ea). Results: In hypertensives, increased LV mass is independently associated with impaired LV function and increased LV filling pressure, whereas increasing degrees of concentric remodeling are associated with attenuated diastolic function but augmented systolic function, possibly representing an adaptive response to pressure overload physiology. Subclinical carotid plaque disease, rather than IMT, is more closely related to LV systolic dysfunction and increased LV filling pressure. Compared to European whites, Indian Asians intrinsically have attenuated longitudinal LV function, higher E/Ea and demonstrate a greater degree of concentric remodeling independent of other demographic and clinical parameters. Despite their lower LV mass, an increased prevalence of LVH amongst Indian Asian men compared to European white men was observed. Conclusions: Novel relationships between biomarkers of subclinical LV geometry, LV function and carotid atherosclerosis have been presented. Given that the burden of carotid atherosclerosis was similar amongst both ethnic groups, this thesis suggests that further research is required into blood pressure aetiology, pro-hypertrophic mediators, end-organ damage and factors involved in acute arterial plaque destabilisation, to further understand the excess risk of CVD in Indian Asians

Imaging biomarkers of subclinical cardiovascular disease in asymptomatic European Whites and Indian Asians : a population study

Background: Subclinical biomarkers of cardiovascular disease (CVD) are being increasingly applied in clinical settings to refine cardiovascular risk stratification and also as an epidemiological tool to enhance the understanding of disease mechanisms. Indian Asians living in the United Kingdom have at least a 50% higher risk of CVD mortality compared to European whites. The excess mortality risk cannot be explained by the pattern of classical risk factors which are generally lower in Indian Asians, and there are no tools that identify their elevated CVD risk. Objectives: To explore potential CVD mechanisms using established and novel imaging biomarkers of subclinical atherosclerosis and left ventricular (LV) function, in a large bi-ethnic cohort of asymptomatic European white and Indian Asian subjects. Mechanisms potentially responsible for the excess CVD mortality observed in UK Indian Asians will also be examined. Methods: A total of 2,439 subjects were recruited from the LOLIPOP study, of which 2,288 were free from clinical CVD. All subjects underwent carotid ultrasonography and echocardiography with tissue Doppler imaging for estimation of LV filling pressure (E/Ea). Results: In hypertensives, increased LV mass is independently associated with impaired LV function and increased LV filling pressure, whereas increasing degrees of concentric remodeling are associated with attenuated diastolic function but augmented systolic function, possibly representing an adaptive response to pressure overload physiology. Subclinical carotid plaque disease, rather than IMT, is more closely related to LV systolic dysfunction and increased LV filling pressure. Compared to European whites, Indian Asians intrinsically have attenuated longitudinal LV function, higher E/Ea and demonstrate a greater degree of concentric remodeling independent of other demographic and clinical parameters. Despite their lower LV mass, an increased prevalence of LVH amongst Indian Asian men compared to European white men was observed. Conclusions: Novel relationships between biomarkers of subclinical LV geometry, LV function and carotid atherosclerosis have been presented. Given that the burden of carotid atherosclerosis was similar amongst both ethnic groups, this thesis suggests that further research is required into blood pressure aetiology, pro-hypertrophic mediators, end-organ damage and factors involved in acute arterial plaque destabilisation, to further understand the excess risk of CVD in Indian Asians.EThOS - Electronic Theses Online ServiceGBUnited Kingdo