Ischemic Cardiomyopathy

Ischemic cardiomyopathy (ICM) is the most commonly identified specific cause of dilated cardiomyopathy, accounting for more than 60% of patients with symptomatic heart failure and many more with asymptomatic left ventricular dysfunction. There are several mechanisms by which coronary artery disease can result in ICM.

Myocardial infarction causes localized myocyte necrosis, with resultant scar formation and loss of contractile function in the ventricular segment perfused by the culprit artery. In addition, the myocardium distal to the area of infarction develops increased wall stress, adverse remodeling, and chamber dilation, so that a cardiomyopathic process occurs in adjacent nonischemic areas.

Another mechanism for myocardial dysfunction is hibernation, in which areas of myocardium are chronically underperfused and metabolically less active. These areas remain metabolically intact but do not contribute to the mechanical activity of the heart. Identification of these areas and restoration of their perfusion through revascularization might improve the ejection fraction and long-term prognosis.

Additional features of ICM include the development of mitral valvular regurgitation, which may be caused by papillary muscle dysfunction or functional factors, such as failure of mitral valve leaflets to coapt in a dilated ventricle. This further increases the volume overload state, increasing myocardial energy demands and causing a vicious cycle of worsening systolic dysfunction.

Atrial and ventricular arrhythmias occur commonly in ICM and include atrial fibrillation, which can further compromise contractile function. The development of atrioventricular conduction delays with the necessity for permanent pacemaker insertion can also cause pacing-induced dyssynchrony when pacing is performed from the right ventricular apex alone.

ICM is generally ascribed to epicardial coronary atherosclerosis, but it can also occur in any vasculitic process (e.g., Takayasu’s arteritis), congenital abnormalities (including aberrant coronary arteries), embolic conditions (e.g., atrial fibrillation, endocarditis, thrombophilic states), cardiac allograft vasculopathy, and microvascular ischemia.

Idiopathic Dilated Cardiomyopathy

The term idiopathic dilated cardiomyopathy is applied to most patients with nonischemic cardiomyopathy. With progress in the field of gene analysis, it is likely that many patients with idiopathic cardiomyopathy will receive a specific molecular or genetic diagnosis in the future.

Acute myocarditis may be a more common prelude to dilated cardiomyopathy than was once believed. The natural history of acute myocarditis is largely unknown because it is rarely symptomatic. It is most commonly caused by Coxsackie group B viruses. Overall, approximately 50% of patients who receive a diagnosis of acute viral myocarditis develop dilated cardiomyopathy. Up to 76% of patients with nonischemic dilated cardiomyopathy who have had a clinically recognized episode of myocarditis have genomic viral DNA persistence in myocardial samples. Despite this, endomyocardial biopsy (EMB) rarely shows myocarditis in patients with new-onset cardiomyopathy. Most have nonspecific histologic findings by light microscopy. There is significant interobserver variability in the pathologic diagnosis of myocarditis.⁴

No specific genetic abnormality is recognized as causing dilated cardiomyopathy. Numerous abnormalities have been found. There are many putative mechanisms in the development of familial cardiomyopathy beyond the scope of this chapter; all forms of mendelian inheritance have been observed, including autosomal dominant, recessive, X-linked, and mitochondrial (matrilinear).⁵

Hypertensive heart disease can initially manifest as left ventricular hypertrophy with isolated diastolic dysfunction and preserved systolic function, as assessed by conventional echocardiographic techniques. Because remodeling occurs over time, the hypertrophy can progress to a dilated cardiomyopathy with systolic dysfunction. Atrial fibrillation is a common manifestation of hypertensive heart disease. Hypertensive heart disease is the leading identifiable cause of heart failure in older women.

Valvular Heart Disease

Hemodynamically significant valvular lesions, such as aortic stenosis, aortic regurgitation, and mitral regurgitation, produce pressure and volume overload states that can result in adverse ventricular remodeling and the development of systolic, diastolic, or combined myocardial dysfunction. In valvular disease, excess hemodynamic demands result in myocyte hypertrophy, subsequent chamber enlargement, and myocardial fibrosis. Chamber dilation then creates or exacerbates existing mitral or tricuspid valvular regurgitation, or both. With further chamber dilation, subendocardial ischemia and localized myocyte necrosis develop. In addition, concomitant coronary artery disease, especially with degenerative aortic stenosis, and atrial fibrillation, especially with mitral regurgitation, can cause further deterioration. (Specific valvular lesions are discussed in the chapters on valvular heart disease.)

Toxic Cardiomyopathies

Alcoholic cardiomyopathy may account for approximately 4% of all cardiomyopathies, and men have a significantly worse prognosis.⁶ The average duration of heavy drinking (more than 90 g/day) in most cohorts is 15 years. Diastolic dysfunction usually precedes any evidence of systolic dysfunction. Left ventricular dilation is an early finding. Hypertension, atrial fibrillation (holiday heart), and coronary disease are more common in heavy drinkers. Identification of alcohol as a potential cause of cardiomyopathy is vital; abstinence can result in an improved ejection fraction in 50% of patients medically treated for heart failure, and continued drinking can result in further deterioration of cardiac function. The mechanism of alcohol-induced cardiomyopathy is unclear but might involve disturbances in intracellular calcium transients, mitochondrial disruption, decreased myofibrillary proteins, and myocyte apoptosis. Histologic findings are nonspecific.

Cocaine and amphetamines (including 3,4-methylenedioxymethamphetamine, or ecstasy) can result in dilated cardiomyopathy with single and chronic use.⁷ The cause is multifactorial and includes direct myocyte toxicity, tachycardia-induced injury, hypertension, and myocardial infarction.

Doxorubicin can cause cardiomyopathy with characteristic histopathologic features. Trastuzumab, used in the treatment of metastatic breast cancer, can cause a cardiomyopathy. Unlike anthracycline-induced toxicity, it usually responds to standard treatment or the discontinuation of trastuzumab.⁸ Brain natriuretic peptide (BNP) is proving useful in monitoring cardiac function in patients receiving cardiotoxic chemotherapy, because elevation of the BNP level occurs at an early stage in the condition. Hydroxychloroquine can cause skeletal and cardiac myopathies.

Peripartum cardiomyopathy is dilated cardiomyopathy arising in the last month of pregnancy or within 5 months postpartum.⁹ Of these cases, 75% occur in the first 2 months after delivery. Risk factors include age older than 30 years, multiparity, twin pregnancy, African descent, and a family history of peripartum cardiomyopathy.¹⁰ Its cause is unknown but may be related to reduced suppressor T cell activity, which occurs during pregnancy, and can result in an autoimmune type of myocardial inflammation or activation of myocarditis. Recovery, usually within 6 months, occurs in 50% of patients. Patients should be advised not to have more children. (See the chapter “Pregnancy and Heart Disease.”)