Faculty Bibliography

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.

BACKGROUND: The prevalence and significance of right ventricular dysfunction (RVD) in patients with cardiogenic shock due to acute myocardial infarction (AMI-CS) has not been well characterized. We hypothesized that RVD is common in AMI-CS and associated with worse clinical outcomes. METHODS AND RESULTS: We retrospectively analyzed patients with available hemodynamics enrolled in the SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK (SHOCK) Trial (n=139) and Registry (n=258) to identify RVD in AMI-CS. RVD was defined by an elevated central venous pressure (CVP), elevated CVP/ pulmonary capillary wedge pressure (PCWP) ratio, decreased pulmonary artery pulsatility index (PAPi), and decreased right ventricular stroke work index (RVSWI). A p value of less than 0.01 was used to infer significance. In both the SHOCK trial and registry, 38% and 37% of patients had RVD, however RVD was not associated with 30-day or 6-month survival (HR 1.51 (0.92, 2.49) p=0.10). RV failure using inclusion criteria from the Recover Right Trial for RV failure (RR-RVF) requiring percutaneous mechanical circulatory support included an elevated CVP, CVP/PCWP ratio, and a low cardiac index despite >/=1 inotrope or vasopressor. In both the SHOCK trial and registry, 45% (n=63/139) and 38% (n=98/258) of patients met RR-RVF criteria respectively. The RR-RVF criteria were not significantly associated with 30-day mortality in the registry cohort (HR 1.44 (1.01,2.04), p=0.04), or in the trial cohort (HR 1.51(0.92,2.49), p=0.10). CONCLUSIONS: Hemodynamically defined RVD is common in AMI-CS. Routine assessment with PA catherization allows detection of RVD; however, further work is needed to identify interventions that will result in improved outcomes for these patients.