Prognostic Significance of Underlying CAD Etiology in Patients with HF

Several studies have shown that CAD is associated with an increase in mortality rates in patients with HF.30-36 One study assessing angiographic data in patients with HF demonstrated that the extent of CAD in patients with HF and reduced left ventricular ejection fraction (LVEF) provides important prognostic information.37 Data also suggest that the mechanism of sudden death may differ between ischemic and nonischemic HF patients, with acute coronary events representing the major cause of sudden death in HF patients with CAD.38 In the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, CAD was associated with higher in-hospital and post-discharge mortality compared to patients without CAD.33 In the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) trial, patients who experienced an acute coronary syndrome (ACS) during follow-up had a significantly increased risk of death as compared to those who did not experience an ACS.39 These findings further emphasize the importance of accurate differentiation between ischemic and nonischemic causes of HF.

Managing HF in patients with CAD or a history of CAD may be significantly different than managing HF due to primary cardiomyopathy. Antiplatelet agents, smoking cessation, and lipid-lowering therapy are particularly important interventions in patients with HF due to CAD.40 Trials of milrinone,41 amiodarone,18 amlodipine,15 and digoxin suggest that patients with HF in the setting of CAD may have a less favorable outcome than patients with HF from primary cardiomyopathy. Revascularization in highly selected patients with reduced LVEF and significant CAD, particularly those with anginal symptoms, may be associated with improved survival and may be considered in addition to risk modification.33,42-49 No prospective randomized trials of coronary artery bypass surgery have been completed in patients with clinical HF, although the ongoing Surgical Treatment for Ischemic Heart Failure (STICH) and the Heart Failure Revascularization Trial (HEART) studies should clarify the role of revascularization in this population.50,51

Pathophysiology of HF in the Setting of CAD. HF in the setting of CAD is a heterogeneous condition with several factors contributing to LV systolic dysfunction and HF symptoms. After an MI, there is loss of functioning myocytes, development of myocardial fibrosis, and subsequent LV remodeling, resulting in chamber dilatation and neurohormonal activation-all leading to progressive dysfunction of the remaining viable myocardium.49 This well-recognized process may be ameliorated after an acute MI by myocardial revascularization47,49,52-55 and by medical therapy with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor antagonists (ARBs),56,57 beta blockers,58 and aldosterone antagonists.59

The majority of patients surviving a MI have significant atherosclerotic disease in coronary arteries other than the infarct-related vessel.60 Under basal conditions, episodes of reversible myocardial ischemia caused by a severe coronary artery stenosis superimposed on the left ventricle with depressed LVEF may produce transient worsening of LV function. In many patients, HF symptoms, such as dyspnea or fatigue induced by exercise, may represent an anginal equivalent.

Episodes of transient myocardial ischemia may cause prolonged systolic dysfunction that persists after the ischemic insult itself has resolved. This process, called stunning, is similar to the more severe and protracted myocardial stunning that results from coronary occlusion and reperfusion.61

Another important mechanism for systolic dysfunction with additive effects on LV performance is myocardial hibernation,62 a process in which myocardial contraction is reduced in response to chronic reduction in myocardial blood supply.63,64 More than 50% of patients with HF and CAD have evidence of viable but dysfunctional (hibernating) myocardium.65,66 Hibernation may develop as an adaptive response to sustained reduction of myocardial blood flow. Thus, the level of tissue perfusion is sufficient to maintain cellular viability but insufficient for normal contractile function.67 Recent evidence supports the long-held concept that hibernation represents a precarious balance between perfusion and tissue viability that cannot be maintained indefinitely, and that myocardial necrosis will occur eventually if blood flow is not increased.62

In addition to ischemia, hibernating myocardium should be considered in all patients with CAD and chronic LV systolic dysfunction of any degree.68 Hibernating myocardium can be identified using low-dose dobutamine stress echocardiography to assess contractile reserve, single photon emission tomography with thallium-201 or technetium-99m perfusion tracers to assess membrane integrity, and positron emission tomography (PET) to assess residual metabolic activity.69,70 Magnetic resonance imaging (MRI) has also been used to identify potentially viable but dysfunctional myocardium.71

Identification of hibernating myocardium is important, as the restoration of blood flow by revascularization or with agents that improve endothelial function and blood flow (eg, statins) may improve contractility in hibernating areas.72-75 However, it should be noted that current testing modalities are limited in their ability to identify areas that will recover with revascularization.