End-Stage Cardiomyopathy Due to Coronary Artery Disease

End-stage coronary artery disease (CAD) typically manifests as a dilated cardiomyopathy, commonly termed ischemic cardiomyopathy (ICM). The patient has known CAD combined with significant left ventricular (LV) systolic dysfunction with an ejection fraction of 35% or less. The most common clinical presentation is that of a patient with a prior history of one or more myocardial infarctions (MIs) who now on echocardiographic evaluation has evidence of significant LV dysfunction. Occasionally (7% in one series), patients present with new symptoms of heart failure (HF) and dilated cardiomyopathy but with no prior history of CAD. These patients, on coronary angiography, typically have multivessel disease. The extent of the coronary atherosclerosis is inversely related to the long-term prognosis.

The pathophysiology of ICM is caused by ischemic damage to the myocardium. In many patients, this triggers a process called ventricular remodeling, which results in alteration of LV architecture, with changes in LV shape and increases in LV volume. The process, following a MI, is depicted in Fig. 46.1 . The changes leading to the macroscopic manifestation of a dilated and dysfunctional LV are complex and are directly proportional to the size of the initial insult.

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Mechanism of progressive left ventricular remodeling after a myocardial infarction (see text).

Reproduced with permission from Konstam MA, et al: Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment, JACC Cardiovasc Imaging 4(1):98–108, 2011.

After the initial infarct event, there is first an inflammatory phase that replaces necrotic myocytes with fibrotic tissue that evolves into a scar. Neovascularization occurs in an attempt to reestablish perfusion to the area and border zone where some surviving myocytes may recover function. Both at a local level within cardiac cells and in the patient’s circulatory system, there is significant activation of the sympathetic nervous system, the renin–angiotensin–aldosterone system, and other regulatory mechanisms that may promote remodeling. Depending on the size of the initial insult and the repair process, there are varying levels of myocyte elongation, scar zone expansion, and thinning of the infarcted area (see Fig. 46.1 ). Most of these changes are adaptive to maintain cardiac output.

As the LV chamber enlarges, important changes occur in myocytes and fibrocytes outside the infarct zone. The upregulation of neuroendocrine factors and changes in loading conditions trigger changes in the myocyte causing elongation hypertrophy, cellular genetic reprogramming, loss of myofilaments, and other functional changes within the cells. Fibroblast proliferation among areas of infarcted myocytes produces replacement fibrosis (see Fig. 46.1 ). Outside of the infarct zone, some fibroblasts are stimulated to evolve into myofibroblast cells that produce considerable fibrous material causing excessive reactive fibrosis. This can cause increased cardiac stiffness, abnormal relaxation, and reduced contractile function. The combination of all of these factors can change initial adaptive remodeling to long-term maladaptive remodeling. The end result is an ICM with secondary LV hypertrophy, chamber enlargement, LV shape changes, and diastolic dysfunction ( Fig. 46.2 ).

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A, Ischemic cardiomyopathy (ICM) in the apical four-chamber view. Left ventricular (LV) enlargement is moderate. Some areas of the LV contract normally. B, ICM in the apical four-chamber view. LV enlargement is severe; all segments are akinetic or hypokinetic. (See Video 46.2A , Video 46.2B
.)

Video 46.2. A, Ischemic cardiomyopathy (ICM) in the apical four-chamber view. Left ventricular (LV) enlargement is moderate. Some areas of the LV contract normally. B, ICM in the apical four-chamber view. LV enlargement is severe; all segments are akinetic or hypokinetic.

A key differentiating process for ICM is to determine whether all of the remodeling changes are irreversible because of permanent changes from replacement fibrosis or if some of the dysfunction is caused by a mechanical loss of contractility in myocytes that remain viable. The discovery of “hibernating myocardium” by viability testing is a situation in which mechanical dysfunction may improve after revascularization. This can be evaluated by several types of multimodality imaging examinations, such as positron emission tomography, cardiac magnetic resonance imaging (MRI), and dobutamine stress echocardiography (see Chapter 54 ). Prior studies have shown that restoration of contractility in hibernating segments of the LV after revascularization may help slow down or partially reverse maladaptive remodeling.

Echocardiography plays a central role in the evaluation of the left ventricle at the time of the baseline event, serially during the course of recovery from an initial MI, and onward as long-term guideline-directed medical and device therapy is initiated.