Faculty Bibliography

OBJECTIVES/OBJECTIVE:The aim of this study was to determine whether frailty is associated with increased bleeding risk in the setting of acute myocardial infarction (AMI). BACKGROUND:Frailty is a common syndrome in older adults. METHODS:Frailty was examined among AMI patients ≥65 years of age treated at 775 U.S. hospitals participating in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry from January 2015 to December 2016. Frailty was classified on the basis of impairments in 3 domains: walking (unassisted, assisted, wheelchair/nonambulatory), cognition (normal, mildly impaired, moderately/severely impaired), and activities of daily living. Impairment in each domain was scored as 0, 1, or 2, and a summary variable consisting of 3 categories was then created: 0 (fit/well), 1 to 2 (vulnerable/mild frailty), and 3 to 6 (moderate-to-severe frailty). Multivariable logistic regression was used to examine the independent association between frailty and bleeding. RESULTS:Among 129,330 AMI patients, 16.4% had any frailty. Frail patients were older, more often female, and were less likely to undergo cardiac catheterization. Major bleeding increased across categories of frailty (fit/well 6.5%; vulnerable/mild frailty 9.4%; moderate-to-severe frailty 9.9%; p < 0.001). Among patients who underwent catheterization, both frailty categories were independently associated with bleeding risk compared with the non-frail group (vulnerable/mild frailty adjusted odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.23 to 1.44; moderate-to-severe frailty adjusted OR: 1.40, 95% CI: 1.24 to 1.58). Among patients managed conservatively, there was no association of frailty with bleeding (vulnerable/mild frailty adjusted OR: 1.01, 95% CI: 0.86 to 1.19; moderate-to-severe frailty adjusted OR: 0.96, 95% CI: 0.81 to 1.14). CONCLUSIONS:Frail patients had lower use of cardiac catheterization and higher risk of major bleeding (when catheterization was performed) than nonfrail patients, making attention to clinical strategies to avoid bleeding imperative in this population.

BACKGROUND:Patients with chronic kidney disease (CKD) and stable ischemic heart disease are at markedly increased risk of cardiovascular events. Prior trials comparing a strategy of optimal medical therapy (OMT) with or without revascularization have largely excluded patients with advanced CKD. Whether a routine invasive approach when compared with a conservative strategy is beneficial in such patients is unknown. METHODS:or on dialysis) and moderate or severe ischemia on stress testing. Participants were randomized in a 1:1 fashion to the invasive or a conservative strategy. The primary end point is a composite of death or nonfatal myocardial infarction. Major secondary endpoints are a composite of death, nonfatal myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest; angina control; and disease-specific quality of life. Safety outcomes such as initiation of maintenance dialysis and a composite of initiation of maintenance dialysis or death will be reported. The trial is projected to have 80% power to detect a 22% to 24% reduction in the primary composite end point with the invasive strategy when compared with the conservative strategy. CONCLUSIONS:ISCHEMIA-CKD will determine whether an initial invasive management strategy improves clinical outcomes when added to OMT in patients with advanced CKD and stable ischemic heart disease.

BACKGROUND:Elevated stress is associated with adverse cardiovascular disease outcomes and accounts in part for the poorer recovery experienced by women compared with men after myocardial infarction (MI). Psychosocial interventions improve outcomes overall but are less effective for women than for men with MI, suggesting the need for different approaches. Mindfulness-based cognitive therapy (MBCT) is an evidence-based intervention that targets key psychosocial vulnerabilities in women including rumination (i.e., repetitive negative thinking) and low social support. This article describes the rationale and design of a multicenter randomized controlled trial to test the effects of telephone-delivered MBCT (MBCT-T) in women with MI. METHODS:We plan to randomize 144 women reporting elevated perceived stress at least two months after MI to MBCT-T or enhanced usual care (EUC), which each involve eight weekly telephone sessions. Perceived stress and a set of patient-centered health outcomes and potential mediators will be assessed before and after the 8-week telephone programs and at 6-month follow-up. We will test the hypothesis that MBCT-T will be associated with greater 6-month improvements in perceived stress (primary outcome), disease-specific health status, quality of life, depression and anxiety symptoms, and actigraphy-based sleep quality (secondary outcomes) compared with EUC. Changes in mindfulness, rumination and perceived social support will be evaluated as potential mediators in exploratory analyses. CONCLUSIONS:If found to be effective, this innovative, scalable intervention may be a promising secondary prevention strategy for women with MI experiencing elevated perceived stress.

BACKGROUND:Prior trials comparing a strategy of optimal medical therapy with or without revascularization have not shown that revascularization reduces cardiovascular events in patients with stable ischemic heart disease (SIHD). However, those trials only included participants in whom coronary anatomy was known prior to randomization and did not include sufficient numbers of participants with significant ischemia. It remains unknown whether a routine invasive approach offers incremental value over a conservative approach with catheterization reserved for failure of medical therapy in patients with moderate or severe ischemia. METHODS:The ISCHEMIA trial is a National Heart, Lung, and Blood Institute supported trial, designed to compare an initial invasive or conservative treatment strategy for managing SIHD patients with moderate or severe ischemia on stress testing. Five thousand one-hundred seventy-nine participants have been randomized. Key exclusion criteria included estimated glomerular filtration rate (eGFR) <30 mL/min, recent myocardial infarction (MI), left ventricular ejection fraction <35%, left main stenosis >50%, or unacceptable angina at baseline. Most enrolled participants with normal renal function first underwent blinded coronary computed tomography angiography (CCTA) to exclude those with left main coronary artery disease (CAD) and without obstructive CAD. All randomized participants receive secondary prevention that includes lifestyle advice and pharmacologic interventions referred to as optimal medical therapy (OMT). Participants randomized to the invasive strategy underwent routine cardiac catheterization followed by revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, when feasible, as selected by the local Heart Team to achieve optimal revascularization. Participants randomized to the conservative strategy undergo cardiac catheterization only for failure of OMT. The primary endpoint is a composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest. Assuming the primary endpoint will occur in 16% of the conservative group within 4 years, estimated power exceeds 80% to detect an 18.5% reduction in the primary endpoint. Major secondary endpoints include the composite of CV death and nonfatal MI, net clinical benefit (primary and secondary endpoints combined with stroke), angina-related symptoms and disease-specific quality of life, as well as a cost-effectiveness assessment in North American participants. Ancillary studies of patients with advanced chronic kidney disease and those with documented ischemia and non-obstructive coronary artery disease are being conducted concurrently. CONCLUSIONS:ISCHEMIA will provide new scientific evidence regarding whether an invasive management strategy improves clinical outcomes when added to optimal medical therapy in patients with SIHD and moderate or severe ischemia.

Four decades ago, U.S. life expectancy was within the same range as other high-income peer countries. However, during the past decades, the United States has fared worse in many key health domains resulting in shorter life expectancy and poorer health-a health disadvantage. The National Heart, Lung, and Blood Institute convened a panel of national and international health experts and stakeholders for a Think Tank meeting to explore the U.S. health disadvantage and to seek specific recommendations for implementation research opportunities for heart, lung, blood, and sleep disorders. Recommendations for National Heart, Lung, and Blood Institute consideration were made in several areas including understanding the drivers of the disadvantage, identifying potential solutions, creating strategic partnerships with common goals, and finally enhancing and fostering a research workforce for implementation research. Key recommendations included exploring why the United States is doing better for health indicators in a few areas compared with peer countries; targeting populations across the entire socioeconomic spectrum with interventions at all levels in order to prevent missing a substantial proportion of the disadvantage; assuring partnership have high-level goals that can create systemic change through collective impact; and finally, increasing opportunities for implementation research training to meet the current needs. Connecting with the research community at large and building on ongoing research efforts will be an important strategy. Broad partnerships and collaboration across the social, political, economic, and private sectors and all civil society will be critical-not only for implementation research but also for implementing the findings to have the desired population impact. Developing the relevant knowledge to tackle the U.S. health disadvantage is the necessary first step to improve U.S. health outcomes.