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Cardiomyopathy is a general term for diseases of the heart muscle (myocardium) that impair its ability to circulate the blood. The cardiomyopathies are not the result of hypertension, congenital heart problems, diseases of the valves, or the coronary arteries. Unlike many heart diseases that are typically associated with aging, cardiomyopathy strikes people of all ages, and very commonly young people. There are two forms: primary and secondary cardiomyopathies. Both forms are diseases of the heart muscle. The primary form has no known cause and the secondary has a known cause or is associated with diseases of other organ systems. A more useful classification is to describe the disease based on its clinical presentation. This classification describes the cardiomyopathy as dilated (congestive), hypertrophic, or restrictive. They vary greatly in symptoms and treatment. The causes of dilated cardiomyopathy can be unknown (idiopathic). Secondary causes are infections, toxins (commonly alcohol and cocaine), endocrine problems such as diabetes and thyroid disease, nutritional, neuromuscular diseases like muscular dystrophy, genetic/familial disease, or as a complication of pregnancy or childbirth (peripartum cardiomyopathy). Dilated cardiomyopathy is found most often in middle-aged men. It is also seen in females following pregnancy.In hypertrophic cardiomyopathy, the heart is enlarged, but the heart findings are reversed. The muscular walls are extremely thick, creating less room inside the ventricular cavities. This condition often has a negative effect on the mitral valve and the septum (the wall between the two ventricles). Hypertrophic cardiomyopathy is inherited in about 50% of cases, and found mostly in individuals between 20 and 40 years old. Restrictive cardiomyopathy, the least common form of this disease, is typically a complication of amyloidosis, a disorder that is associated with cancers of the blood. It can be difficult to distinguish restrictive cardiomyopathy from constrictive pericarditis, which is curable with surgery.

History: Individuals with dilated cardiomyopathy may report shortness of breath (dyspnea) on exertion, breathing difficulties while lying down (orthopnea), or sleeping (paroxysmal nocturnal dyspnea), fatigue, and occasionally palpitations. Many individuals with hypertrophic cardiomyopathy, especially children and young adults, have no symptoms of the disease. The disease is discovered after a sudden death on post-mortem examination. Symptoms in other individuals include shortness of breath, dizziness or fainting, chest pain, and an awareness of heart palpitations. Shortness of breath (dyspnea) on exertion and fatigue are the most prominent symptoms of restrictive cardiomyopathy. Other symptoms include an increased abdominal girth, swelling of the feet and ankles, and upper abdominal discomfort due to swelling of the liver. In individuals with restrictive cardiomyopathy secondary to infiltrative diseases such as amyloidosis and sarcoidosis, syncope (fainting) or near syncope and sudden death may be the presenting symptom. Physical exam: The individual with dilated cardiomyopathy often appears breathless and pale and has a difficulty in breathing while lying recumbent. Tachycardia (fast heart rate) and extra beats (ectopic beats) while listening to the heart are common. There may be wheezing and other chest findings consistent with heart failure. The only finding on physical exam in individuals with hypertrophic cardiomyopathy may be a systolic heart murmur that changes in character with different physical tests (squatting, Valsalva maneuver) and stressing the heart with drugs such as amyl nitrate or nitroglycerin. Common physical findings with restrictive cardiomyopathy are swelling of the ankles and feet, fluid in the abdomen (ascites), and an enlarged tender liver. The heart sounds are distant with extra sounds (gallops). Tests: An electrocardiogram, angiogram, chest x-ray, and echocardiogram may be necessary to confirm diagnosis of cardiomyopathy. Cardiac catheterization with myocardial biopsy is an option when the diagnosis is unclear.

Individuals with dilated cardiomyopathy are often started on drug therapy, which may include digitalis, vasodilators, diuretics, and steroids. Cardiomyopathies attributable to infections are treated with the appropriate antimicrobials. Treatment may include anticoagulants to reduce the risk of blood clots. Some individuals may not respond to drug therapy. A heart transplant is indicated in the most serious case, if all the other criteria for transplantation surgery are met. The drug regimen for hypertrophic cardiomyopathy often adds beta-receptor and calcium channel blockers. If the treatment is not successful, the individual may benefit from implantation of a defibrillator device. Some individuals may require surgery to remove excess myocardial tissue in the intraventricular septum. Although the procedure has a

mortality rate of about five-percent, the majority of individuals see dramatic, long-term improvement. In rare cases, a heart transplant is recommended. In individuals with restrictive cardiomyopathy, drug therapy is usually attempted but is often unsuccessful. Most individuals who display signs of heart failure die within a year.In addition to the specific therapies outlined above, individuals with all types of cardiomyopathy are usually urged to make lifestyle changes. Restriction of salt and abstention from alcohol are important dietary changes. Obesity must be addressed. Cessation of smoking reduces the workload on the heart. MEDICATIONS Brand Name Lasix Tenormin Accupril Betapace Capoten Coreg Vasotec Inderal Microzide Aldactone Altace Norvasc Lopressor Cozaar Coumadin Adalat Cordarone Isoptin Diovan Atacand CONGESTIVE CARDIOMYOPATHY Metoprolol Losartan HYPERTROPHIC CARDIOMYOPATHY Warfarin Nifedipine Amiodarone Verapamil ALCOHOLIC CARDIOMYOPATHY Valsartan Candesartan Active Ingredient Furosemide ISCHEMIC CARDIOMYOPATHY Atenolol Quinapril Sotalol Captopril Carvedilol Enalapril Propranolol Hydrochlorothiazide PERIPARTUM CARDIOMYOPATHY Spironolactone Ramipril Amlodipine


In dilated cardiomyopathy, the heart is enlarged with flabby, weak walls and significantly dilated ventricles. Because the heart pumps so poorly, clots (thrombi) often develop in the heart. This increases the individual's risk of stroke and other embolic phenomena attacks. Hypertrophic cardiomyopathy can result in the condition known as atrial fibrillation. These individuals are at risk of forming thrombi in the left atrium with the same risk of complications seen with dilated cardiomyopathy. Though the individuals with restrictive cardiomyopathy need diuretics to help with right-sided heart failure, they are at risk of developing hypotension, even with careful monitoring. Whatever the cause or type of cardiomyopathy, any individual with cardiomyopathies is more prone to complications from pneumonia and other systemic diseases that are less innocuous in healthy individuals. This overview of possible complications is by no means comprehensive.

The prognosis for individuals with dilated cardiomyopathy depends in large part on their age and whether the disease is considered to be of recent onset. The majority of individuals, especially when they are 55 or older at diagnosis, die within a few years. Younger individuals may do quite well, either because of spontaneous reversal or because of drug therapy. Both hypertrophic and restrictive cardiomyopathies have high mortality rates.

Dilated cardiomyopathy is similar to the findings seen in cases of congestive heart failure secondary to ischemic heart disease. Hypertensive heart disease presents similarly and has many of the same symptoms and signs of hypertrophic cardiomyopathy. Restrictive cardiomyopathy is difficult to distinguish from constrictive pericarditis.

Cardiologist and cardiovascular surgeon.

Treatment of Peripartum Cardiomyopathy

Dennis M. McNamara, MD
Heart Failure Section, Cardiovascular Institute of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA INTRODUCTION Peripartum cardiomyopathy (PPCM) is a rare but serious complication of pregnancy with an incidence in published series of 1:1300 to 1:4000 live births (1). This disorder classically presents in the time interval from the last month of pregnancy until 6 months after delivery, with the majority of cases presenting in the early postpartum period (2). Other than the precipitating factor of pregnancy, PPCM is clinically identical to other forms of primary dilated cardiomyopathy (3,4). Medical therapy is primarily the standard treatment of heart failure due to systolic dysfunction, however, its presentation in young women of childbearing age presents some unique challenges. In this lecture, we shall present briefly the current understanding of the pathogenesis of peripartum cardiomyopathy, medical management, and the potential future roles of investigative therapies. PATHOGENESIS As in other forms of primary dilated cardiomyopathy, the etiology remains uncertain, however, evidence points towards an inflammatory pathogenesis. The reported incidence of cellular myocarditis on endomyocardial biopsy varies from 9% to 78% (5,6,7,8) and this wide variation is similar to that seen in idiopathic dilated cardiomyopathy (IDCM). Multiparity is a risk factor for the development of this disorder, suggesting that previous exposure to fetal or paternal antigen may elicit an abnormal myocardial inflammatory response. The timing of presentation in the immediate postpartum period supports an autoimmune pathogenesis. Adaptive changes in the maternal immune system allows the fetal tolerance necessary for successful pregnancy and include the induction of suppressor cells (9,10). These adaptive changes likely underlie the clinical observation that autoimmune disorders such as multiple sclerosis which affect women during their reproductive years typically have lower relapse rates during pregnancy itself, with a marked increase in the immediate postpartum period (11). The majority of cases of peripartum cardiomyopathy present in this same early postpartum period in which restoration of the maternal immune system results in an increase in autoimmune exacerbations in other disorders. An alternative to the inflammatory theory is that of a latent cardiomyopathy brought to fruition by the hemodynamic stresses of pregnancy. Hypertension during pregnancy, and in particular preeclampsia, are both reported in a higher frequency of women with peripartum cardiomyopathy and do support that hemodynamic stresses may play a role. However, given the normal hemodynamic changes of pregnancy, most women with compromised cardiac function, such as valvular heart disease, present with symptoms of heart failure by the end of the second trimester, and the absence of cardiac symptoms in PPCM until the postpartum period argues against the "latent cardiomyopathy" theory.

PRESENTATION AND EVALUATION Shortness of breath, orthopnea, and paroxysmal nocturnal dyspnea in the recent postpartum period are the most common presenting symptoms. Fatigue is also quite common. While this is frequently dismissed and attributed to the demands of caring for a new infant, women with prior pregnancies may note fatigue out of proportion to their previous postpartum experience. Chest discomfort is usually more characteristic of pulmonary congestion than angina. Peripheral edema is often a manifestation of volume overload, however, when associated with other signs of right heart failure and hepatic congestion may suggest more serious right ventricular involvement. Persistence of pulmonary complaints frequently leads to chest x-ray evaluation, particularly in the postpartum period. The finding of interstitial or alveolar edema, occasionally with associated cardiomegaly, may lead to the initial diagnosis. Electrocardiogram findings are generally non-specific and include poor R-wave progression, intraventricular conduction delay, and non-specific ST and Twave changes. Laboratory evaluation usually reveals little or no elevation in creatinine kinase, or cardiac troponin. In women with acute heart failure and hemodynamic compromise, assessment of liver function tests, and renal function provides an assessment of an organ perfusion. In contrast to myocarditis, fever and leukocytosis is uncommon and when present should elicit a thorough evaluation for postpartum sepsis as an alternative diagnostic possibility. Echocardiography remains an important tool for evaluation and follow-up for women with postpartum cardiomyopathy. The finding of a decrease in myocardial systolic dysfunction, as manifest by a decrease in left ventricular ejection fraction or fractional shortening is essential to the diagnosis. Left ventricular dilatation is also frequently evident, particularly in those women presenting late. Mild compensatory left ventricular hypertrophy can be seen, however, marked increases in LV wall thickness may suggest primary hypertrophic cardiomyopathy, an entity with a very distinct natural history and prognosis. A small pericardial effusion may be seen in the early and presumably more inflammatory immediate postpartum period. Valvular morphology is generally normal, however, with marked LV enlargement mitral regurgitation secondary to annular dilatation may be seen. Overall, echocardiographic features of postpartum cardiomyopathy are indistinguishable from those of primary non-ischemic dilated cardiomyopathy. Initial evaluation should rule out other potential causes of heart failure. The most common alternative diagnosis, occult valvular heart disease, can be effectively ruled out by transthoracic echocardiography. The finding of normal systolic function excludes postpartum cardiomyopathy and should lead to an evaluation for forms of high output failure such as anemia and thyrotoxicosis. Although ischemic heart disease is uncommon in this population, women with significant risk factors such as Type I diabetes should have at least a non-invasive assessment for coronary ischemia, and if questions persist should undergo angiography. In women with persistent heart failure, hemodynamic instability or evidence of an organ dysfunction, right heart catheterization to assess filling pressures and cardiac output should be considered. Although some tertiary centers do perform endomyocardial biopsy to assess for cellular inflammation, this finding is of limited prognostic value and as it generally does not change therapeutic recommendations, its use has markedly decreased in frequency in recent years. PROGNOSIS: POTENTIAL FOR RECOVERY Whileperipartum cardiomyopathy shares many features of other forms of non-ischemic dilated cardiomyopathy, an important distinction is that women with this disorder have a much higher rate of spontaneous recovery of left ventricular function. As many as 50% of women presenting with this disorder will normalize their ejection fraction during subsequent follow-up, (12) most within the first six months. This higher rate of spontaneous recovery compared to other forms of IDCM likely reflects differences in timing, not in pathogenesis. Patients presenting with idiopathic dilated cardiomyopathy may do so months to years after the initial myocardial injury, long after the time for spontaneous recovery has past. In contrast, for women presenting with peripartum cardiomyopathy, the timing of the initiating event is clear. As women present in the acute phase of the illness, there is a greater

chance of spontaneous recovery once the hemodynamic or "inflammatory" stress of pregnancy resolves. Prognosis is directly correlated to recovery of left ventricular function. For those women whose LVEF normalizes during follow-up their prognosis is excellent as without the stimulus of a subsequent pregnancy the chance of development of heart failure or future LV dysfunction is minimal. For those women whose left ventricular function does not recover, prognosis remains guarded and mortality rates as high as 10-50% in some series have been reported (13,14). Few clinical clues exist which help predict which women will recover their LV function. Our experience suggests that LV size is an important predictor, as women presenting without significant LV dilatation appeared to have a greater chance of spontaneous recovery during follow-up. In contrast, women with marked LV dilatation at presentation appeared to have a greater likelihood of developing into a chronic cardiomyopathy. Initial NYHA class or hemodynamics do not seem to predict the likelihood of subsequent recovery. Women who remain severely functionally limited or inotrope dependent despite therapy should be evaluated for possible cardiac transplantation, however, we attempt to delay transplantation if possible for the first six months postpartum in the hopes that some recovery of LV function will allow transplant to be deferred. MEDICAL MANAGEMENT The medical management of peripartum cardiomyopathy is similar to other forms of heart failure due to systolic dysfunction with the exception that in women presenting during pregnancy, potential effects to the fetus must be considered (15,16). Therapy with angiotensin converting enzyme inhibitor are the core of therapy of women postpartum, but are contraindicated during pregnancy itself due to potential teratogenic effects ACE inhibitor use during pregnancy, particularly in the second and third trimester, has been associated with increased fetal loss and a fetopathy characterized by fetal hypotension, oligohydramnios-anuria and renal tubular dysplasia. Angiotensin receptor antagonist (ARB's) while a reasonable alternative to ACE inhibitor therapies postpartum, should be similarly avoided during pregnancy due to potential adverse effects. For women presenting during pregnancy with symptoms of congestion due to cardiomyopathy, a loop diuretic can be utilized generally at the lowest effective dose. A small daily dose of digoxin can be added. In terms of afterload reduction, hydralazine and nitrates can be used as an alternative. Despite the growing evidence of the effectiveness of beta receptor antagonist (beta blockers) as heart failure therapy, less is known about their effectiveness for PPCM and their use must be individualized. In terms of safety, there is a long history of the use of beta blocker therapy in treating pregnant women with hypertension without any known adverse effects to the developing fetus, and for patients on these agents prior to diagnosis, they can be safely continued. For patients presenting postpartum, ACE inhibitor therapy should be initiated. In those patients not tolerating ACE inhibitors due to cough, ARB's are an acceptable alternative. Symptoms of congestion should be treated with a loop diuretic and digoxin. For patients who remain symptomatic despite ACE inhibitor and diuretic therapy, beta blocker therapy can be initiated. These should be used with caution in the occasional acute patient who presents with significant systolic dysfunction without ventricular enlargement. These patients with normal LV chamber size have a markedly reduced stroke volume, and occasionally the reductions in heart rate associated with beta blocker therapy are poorly tolerated. Like other forms of heart failure, this syndrome can lead to thrombotic and embolic complications. Patients with evidence of a systemic embolus, or with severe left ventricular dysfunction and documented mural thrombus, anticoagulation should be considered. Warfarin therapy is contraindicated during pregnancy and for women requiring anticoagulation, heparin must be utilized. Postpartum, in patients with either a clinical embolic event or with ultrasound evident of thrombus formation, Warfarin therapy should be utilized for a period of six months. The need for chronic anticoagulation should then be reassessed depending on the state of LV recovery. As in other forms of non-ischemic dilated cardiomyopathy, ventricular arrhythmias can be an important clinical issue. Patients presenting with sudden death or ventricular tachycardia with

hemodynamic compromise, strong consideration of an ICD is warranted due to the potential for a fatal recurrence. For patients presenting with symptomatic ventricular tachyarrhythmia which are hemodynamically well tolerated, management can be tempered somewhat by the potential transient nature of the myopathy and amiodarone therapy at 200 to 400 mg poqd is an alternative. If left ventricular function recovers, the risk of serious arrhythmic event is markedly diminished and amiodarone therapy can be discontinued. For patients with asymptomatic non-sustained ventricular tachyarrhythmia we would not initiate amiodarone therapy, but would focus on correction of metabolic abnormalities and consider the addition of a beta receptor antagonist if not already being utilized. ACTIVITY AND FOLLOW-UP Although patients are encouraged to remain as active as their functional status allows, aerobic activities and heavy lifting are discouraged for at least the first six months postpartum while assessing the degree of left ventricular recovery. Given the metabolic demands of lactation, breast feeding is strongly discouraged in more symptomatically limited patients. As pharmacologic therapy to the patient can be passed on to the child in breast milk, we also discourage breast feeding in more functional patients, though this could be considered with careful monitoring of the child. In terms of the reassessment of LV function, the echocardiogram should be repeated at 6 months post delivery; for those patients with persistent cardiomyopathy beta blockers should be added at this point if not already on therapy. SPECIAL CONSIDERATIONS - HEMODYNAMIC STRESS OF DELIVERY For patients presenting during the late stages of pregnancy, consideration should be given to limiting the hemodynamic stress of the delivery. Compensated patients may undergo vaginal delivery with appropriate monitoring. For those patients late in pregnancy with more significant hemodynamic compromise, consideration should be given to elective caesarian with invasive hemodynamic monitoring of the mother. RISKS OF SUBSEQUENT PREGNANCIES For patients whose left ventricular function fails to normalize during follow-up, subsequent pregnancies carries a high risk of left ventricular deterioration and progressive heart failure, and is strongly discouraged given the possible risk to the life of the mother. A more difficult question is the risk of subsequent pregnancy in women whose left ventricular function normalized. A recent large retrospective survey suggests that in women with normal ejection fractions at the time of subsequent pregnancy, there was an approximate 21% risk of the development of heart failure (6 of 28), and a drop in the mean ejection fraction from 0.56 to 0.49 (17). However, no serious complications were noted and the majority of those women had a successful delivery at term. This was in marked contrast to the women with persistent LV dysfunction prior to pregnancy in whom 3 deaths out of 16 women (19%) were noted, two occurring soon after delivery and one two years later. Overall, our recommendation is that pregnancy clearly be avoided in women with persistent left ventricular function. Women whose LV function normalizes should still be made aware of the risk of possible recurrence, though in the majority of these women successful pregnancy can be accomplished with appropriate monitoring. IMMUNE MODULATORY THERAPY Given the inflammatory nature of peripartum cardiomyopathy and the occasional appearance of myocarditis on endomyocardial biopsy, immunosuppressive and immune modulatory therapy have been utilized. Medei et al. reported on a series of 18 patients from Johns Hopkins in whom myocarditis was found in 78% and immunosuppressive therapy with prednisone and azathioprine was associated with resolution in 9 of 10 treated patients (7). In a similar fashion, we reported that immune modulatory therapy with high dose intravenous immune globulin (2 gm/kg) in a series of 6 women (with and without myocarditis on biopsy) was associated with a marked improvement in left ventricular function (18). The clinical applicability of both these reports has to be viewed with caution given the absence of a prospective control group. A randomized trial of immunosuppressive therapy in a related population with myocarditis did not prove efficacy in the Myocarditis Treatment Trial, (19) and in a similar fashion therapy with immune globulin did not improve outcomes in a randomized trial of patients with acute cardiomyopathy (IMAC Trial) (20). Neither trial addressed the use of these

agents in peripartum cardiomyopathy. In general, given the high spontaneous recovery rate on conventional therapy, we advise against therapy with either immune globulin or immunosuppression until one assesses how the patient will recover functionally on conventional medical therapy. For patients whose clinical status continues to deteriorate despite maximal medical therapy, alternative therapies including immune modulatory therapy may be considered. THE FUTURE Peripartum cardiomyopathy remains a rare but troubling complication of pregnancy. Current recommended therapy remains the standard pharmacologic treatment for heart failure due to systolic dysfunction, however, outcomes on conventional therapy vary widely. For up to 50% of women marked recovery of ventricular function will be seen during follow-up and standard therapy is all that is needed. However, for the remainder, chronic cardiomyopathy will persist. Future investigations must focus first on clinical and biological predictors of outcomes so that investigative therapy may be targeted to those women predicted not to recover. Given the rarity of this disorder, collaborative international multicenter studies will be of great assistance in the search to improve methodologies to diagnose and treat this troubling disorder. REFERENCES
1. Homans DC, Peripartum cardiomyopathy. N Engl J Med 1985;312:1432-1437. 2. Demakis JG, Rahimtoola SH. Peripartum cardiomyopathy. Circulation 1971;44:964-968. 3. van Hoeven KH, Kitsis RN, Katz SD, Factor SM. Peripartum versus idiopathic dilated cardiomyopathy in young women a comparison of clinical pathologic and prognostic features. International Journal of Cardiology 1993;40:57-65. 4. van Hoeven KH, Kitsis RN, Katz SD, Factor SM. Peripartum versus idiopathic dilated cardiomyopathy in young women a comparison of clinical pathologic and prognostic features1986;67:157-167. 5. Melvin KR, Richardson PJ, Olson EG, et al. Peripartum cardiomyopathy due to myocarditis. N Engl J Med 1982;307:73134. 6. Huerta EM, Erice A, Espino RF, et al. Post-partum cardiomyopathy and acute myocarditis. American Heart Journal 1985;110:1079-1081. 7. Midei MG, DeMent SH, Feldman AM, et al. Peripartum myocarditis and cardiomyopathy. Circulation 1990;81:922-928. 8. Rizeq MN, Rickenbacher PR, Fowler MB, Billingham ME. Incidents of myocarditis in peripartumcardiomypathy. American Heart Journal 1994;74:474-477. 9. Foelich CJ, Goodwin JS, Bankhurst AD, Williams RC. Pregnancy, a temporal fetal graft of suppressor cells in autoimmune disease. The American Journal of Medicine 1980; 69:329-331. 10. Kovithavongs T, Dossetor JB. Suppressor cells in human pregnancy. Transplantation Proceedings 1978;10:911-913. 11. Damek DM, Shuster EA. Pregnancy and multiple sclerosis. Mayo ClinProc 1997;72:977-989. 12. Demakis JG, Rahimtoola SH, Sutton GC, et al. Natural course of peripartum cardiomyopathy. Circulation 1971;44:1053-1061. 13. O'Connell JB, Costanzo-Nordin MR, Subramanian R, et al. Peripartum cardiomyopathy: Clinical hemodynamic, histologic and prognostic characteristics. JACC 1986;8:52-56. 14. Wilin AG, Mabie WC, Sibai BM. Peripartumcardiomypathy: An ominous diagnosis. Am J ObstetGynecol 1997;176:182188. 15. Pearson GD, Veille JC, Rahimtoola S, et al. Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) Workshop Recommendations and Review. JAMA 2000;283:11831188. 16. Vielle JC, Zaccaro D. Peripartumcardiomypathy: Summary of an international survey on peripartum cardiomyopathy. Am J ObstetGynecol 1999;181:315-319. 17. Elkayam U, Padmini PT, Kalpana R, et al. Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy. N Engl J Med 2001;344:1567-1571.

18. Bozkurt B, Villanueva FS, Holubkov R, et al. Intravenous immune globulin in the therapy of peripartum cardiomyopathy. J Am CollCardiol 1999;34:177-180. 19. Mason JW, O'Connell JB, Herskowitz A, et al. A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med 1995;333:269-275. 20. McNamara DM, Holubkov R, Starling RC, et al. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation 2001;103:2254-2259.

Peripartum Cardiomyopathy
Peripartum Cardiomyopathy is a type of disease that can be termed as a rare disorder, where a weak heart can be diagnosed at the very final stages of pregnancy. This disorder can even be identified at the stage where 5 months after the delivery have passed. To discuss about the causes, it ranges from one to many as it occurs depending upon ones condition and also due to some external factors. The main cause of the occurrence is due to the impairment of the heart. This condition leads to a state where the heart becomes too weak to pump the normal amount of blood and thus the functionality of the heart decreases significantly. So as a result, due to this failing condition of the heart, other organs that are totally dependent on the heart will also be affected stage by stage. This peripartum cardiomyopathy is a type that belongs to the dilated cardiomyopathy, wherein no other causes of this heart dysfunction can be seen. It has been observed that one in every 1,300 to 1,400 women are being affected during their delivery period. This condition can be seen in young women who carry their child or it might also occur in women after 30. The factors of discussion of the reasons behind this state are smoking, alcoholism, obesity, history of some cardiac disorders, multiple pregnancies, being malnourished, sometimes being African American and also due to the use of some medications. Some of the symptoms that can be noticed are shortness of breath when busy in any physical activity and also when laying flat, fatigue, swelling of the parts of the ankles, nocturia, which is a condition of increased bed time urination, feeling of skipping heart beats and also a feeling of having a racing heart. To avoid such conditions beforehand, some kind of physical examination should be done. This can be done by a physician. He/she will examine the lungs for the presence of any kind of liquid. Listening to some of the chest beats with the stethoscope will expose the lung crackles, a fast heart rate or irregular heart sounds. The liver might be distended and the neck veins could be inflamed. In addition to these conditions, Blood pressure might be small or could drop when the long-suffering patient stands up. Heart enlargement, blocking of the lungs or veins present in the lungs, decreased cardiac condition and decreased movement can also be witnessed.

Cardiomyopathies are diseases of the myocardium associated with cardiac dysfunction. 1 Table 1 lists the five types of cardiomyopathydilated, hypertrophic, restrictive, arrhythmogenic right ventricular, and unclassified cardiomyopathy. Many conditions manifest as one form of cardiomyopathy and progress to another. For example, hypertensive heart disease may begin with a hypertrophic pattern and subsequently become a dilated cardiomyopathy. Some diseases

may have features of more than one type of cardiomyopathy (e.g., sarcoidosis may have features of restrictive and dilated cardiomyopathy at different times in the course of the disease). Table 1: World Health Organization Classification of Cardiomyopathies Type of Cardiomyopathy Dilated


Causative Factors

Dilated left or both ventricle(s), with impaired contraction

Ischemic, idiopathic, familial-genetic, immune, alcoholic, toxic, valvular Familial, with autosomal dominant inheritance (see elsewhere in this section, Hypertrophic Cardiomyopathy)


Left or right ventricular hypertrophy, or both


Restrictive filling and reduced diastolic filling of one or both ventricles; normal or nearnormal systolic function

Idiopathic, amyloidosis, endomyocardial fibrosis

Arrhythmogenic right ventricular cardiomyopathy

Fibrofatty replacement of right ventricular myocardium, Uhl's anomaly (parchment heart)

Unknown; familial, usually autosomal dominant inheritance, with incomplete penetrance; possible autosomal recessive inheritance; rare forms associated with typical phenotype (e.g., Naxos disease)


Not typical for previous four groups

Fibroelastosis, noncompacted myocardium, systolic dysfunction with minimal dilation, mitochondrial disease

Data from Richardson P, McKenna W, Bristow M, et al: Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation 1996;93:841-842.

Cardiomyopathy frequently results in the heart failure syndrome, with a number of systemic manifestations. On the other hand, many systemic conditions have cardiac involvement and may manifest primarily as heart failure. The cardiomyopathies represent a diverse group of conditions whose final common pathway is myocardial dysfunction. With few exceptions, histologic findings are nonspecific, with myocyte hypertrophy, cellular necrosis, and fibrosis. There are many known causes of cardiomyopathy. Many systemic diseases have myocardial involvement, which can range from mild to severe ( Table 2 ). The most common cause in developed countries is ischemic cardiomyopathy. In other areas, such as equatorial Africa, infiltrative disease is the leading cause.

Table 2: Causes of Cardiomyopathy Cause Cardiovascular Disorder Ischemic heart disease Hypertension Valvular heart disease Idiopathic dilated cardiomyopathy Idiopathic restrictive cardiomyopathy Cardiac amyloidosis Metabolic Starvation, vitamin deficiency Diabetes, hypothyroidism and hyperthyroidism, acromegaly, pheochromocytoma Glycogen storage disease Infectious, inflammatory Secondary amyloidosis, sarcoidosis Acute viral (Coxsackie B), HIV, hepatitis C Chagas' disease (protozoal) Toxic Genetic Alcohol, cocaine, amphetamines, chemotherapy Familial dilated cardiomyopathy Familial cardiac amyloidosis Noncompacted myocardium Systolic dysfunction without dilation Arrhythmogenic right ventricular cardiomyopathy Hemochromatosis Tachycardia Pregnancy
2003 The Cleveland Clinic Foundation.

Tachycardia-induced cardiomyopathy Peripartum cardiomyopathy

In this chapter, discussion will be confined to the definition, prevalence, signs and symptoms, and diagnosis of cardiomyopathies, with the exclusion of hypertrophic cardiomyopathy. Treatment is discussed in the chapter on heart failure.

Dilated cardiomyopathy
This condition may be defined as an ejection fraction of less than 40% in the presence of increased left ventricular dimension (left ventricular end-diastolic size more than 115% of that calculated for age and body surface area). Increased left ventricular dimensions in the presence of preserved systolic function may be a precursor to the development of systolic dysfunction in certain individuals. Pharmacologic intervention with angiotensin-converting enzyme inhibitors and beta blockers may prevent this progression to heart failure in some of these individuals.

It is difficult to assess the prevalence of cardiomyopathy accurately. Many patients with this condition go undiagnosed and may present with sudden cardiac death. Strict diagnostic criteria are lacking. There are approximately 5 million Americans with symptomatic heart failure, but it has been estimated that 50 million Americans fulfill American Heart AssociationAmerican College of Cardiology definitions of classes A and B heart failure ( Table 3 ), 2 who are either at risk for or have established structural heart disease in the absence of heart failure symptoms. It is unclear how many people fall into stages B, C, and D combined (those with structural heart disease, with or without heart failure symptoms); most of these people have cardiomyopathies. Table 3: American Heart Association/American College of Cardiology Staging of Heart Failure Stage A B C D Definition Patients at risk of heart failure, with no structural heart disease Patients with structural heart disease, without symptoms of heart failure Patients with past or present heart failure symptoms Patients with advanced disease (e.g., inotropic support)

Adapted from Hunt SA, Abraham WT, Chin MH, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; American College of Chest Physicians; International Society for Heart and Lung Transplantation; Heart Rhythm Society: ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society. Circulation 2005;112:e154-e235.

The estimated prevalence of idiopathic dilated cardiomyopathy is 0.4 per 1,000 of the general population. However, in the future, as more causes are elucidated and more patients are diagnosed with genetic or familial cardiomyopathy, the number of patients with idiopathic disease, a diagnosis of exclusion, will decrease.

Dilated cardiomyopathy represents the final common morphologic outcome of various biologic insults. It is a combination of myocyte injury and necrosis associated with myocardial fibrosis, which results in impaired mechanical function. Many cases are a result of direct toxicity (e.g., alcohol) or mechanical insults (e.g., chronic volume overload in mitral valvular regurgitation). With myocyte failure and cytoskeletal uncoupling, the chambers become dilated. According to Laplace's law, increased diameter increases wall stress and causes further mechanical disadvantage. Thus, myocardial dysfunction can cause a vicious cycle leading to more myocardial dysfunction in a process termed adverse ventricular remodeling, now an important therapeutic target. 3

Specific Types
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 may 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 may 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 may 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 will 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 There is no specific genetic abnormality recognized as causing dilated cardiomyopathy. Multiple 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, Xlinked, and mitochondrial (matrilinear).

Hypertensive heart disease may 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 may 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, with men having a significantly worse prognosis. 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 may 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. 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-type 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. Of these cases, 75% occur in the first 2 months after delivery. Risk factors include age older than 30 years, multiparity, twin pregnancy, African American descent, and a family history of peripartum cardiomyopathy.
10 9 7 6


cause is unknown but may be related to reduced suppressor T cell activity, which occurs during pregnancy, and may 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 elsewhere in this section, Pregnancy and Heart Disease.)

Infective Cardiomyopathies
In addition to the acute (often presumed viral) myocarditis discussed earlier, various other viral agents have been implicated in the development of cardiomyopathy, including human immunodeficiency virus (HIV) and hepatitis C.Trypanosomacruzi (a protozoan) has infected 20 million people in South and Central America. Infection causes Chagas' disease, a dilated cardiomyopathy (either global or with characteristic apical aneurysm formation) in 20% to 30% of patients, acutely or over many years. Other parasitic infestations that can cause cardiomyopathy in the immunocompetent and immunocompromised patient include Toxoplasma gondii and Trichinellaspiralis. Plasmodium falciparum infection (malaria) can cause parasitic coronary artery occlusion.

Tachycardia-Induced Cardiomyopathy
Prolonged exposure to rapid heart rates can induce myocardial dysfunction. Persistent or permanent atrial fibrillation induces electrical and structural remodeling of the atria. When rapidly conducted, it may cause adverse ventricular remodeling and a dilated cardiomyopathy. The diagnosis is one of exclusion, and rate control or restoration of sinus rhythm may restore systolic function. Sometimes cause and effect can be difficult to determine.

Metabolic Conditions
Malnutrition, as well as selenium, carnitine, phosphate, calcium, and vitamin B deficiencies, can result in dilated cardiomyopathy. Endocrine causes include adrenocortical insufficiency, thyrotoxicosis, hypothyroidism, acromegaly, and pheochromocytoma.

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Restrictive cardiomyopathies
Restrictive cardiomyopathy is a disease of the myocardium characterized by restrictive filling and reduced diastolic volume of either or both ventricles, with normal or near-normal systolic function. 1

These conditions represent a very small proportion (less than 5%) of cardiomyopathies in the West, 11 but are more common in certain populations. For example, endomyocardial fibrosis is a relatively common cause of heart failure in equatorial Africa, whereas ischemic heart disease is not.

These conditions result in impaired ventricular filling and primarily diastolic heart failure. They manifest with a clinical heart failure syndrome frequently indistinguishable from that caused by systolic dysfunction. Atrioventricular block and symptomatic bradycardias can be seen, often necessitating pacemaker insertion. Atrial fibrillation is poorly tolerated. Restrictive cardiomyopathies may be classified as primary (e.g., endomyocardial fibrosis, Lffler's endocarditis, idiopathic restrictive cardiomyopathy) or secondary. Causes of secondary restrictive cardiomyopathy include infiltrative diseases (e.g., amyloidosis, sarcoidosis, radiation carditis) and storage diseases (e.g., hemochromatosis, glycogen storage disorders, Fabry's disease). Fabry's disease, although rare, has assumed a new importance as effective treatment has become available. 12 Amyloid heart disease is classified as primary, secondary, familial, or senile. Primary amyloid heart disease is caused by overproduction of light chain immunoglobulin from a monoclonal population of plasma cells, usually associated

with multiple myeloma. Secondary amyloid heart disease is associated with chronic inflammatory conditions such as Crohn's disease, rheumatoid arthritis, tuberculosis, and familial Mediterranean fever. Familial and senile amyloid heart disease are related to the overproduction of transthyretin. Myocardial amyloid heart disease is confirmed by EMB. The presence of near-normal left ventricular dimensions combined with increased myocardial wall thickness, particularly biventricular thickening, should arouse suspicion of an infiltrative cardiomyopathy, especially if accompanied by low-voltage QRS complexes on the electrocardiogram (ECG). Unfortunately, there is no proven treatment for amyloid heart disease, and the prognosis is poor.13

Specific Types
Hemochromatosis (bronze diabetes) is a disease that results in iron overload and deposition of iron in the sarcoplasmic reticulum of many organs, including the heart. It generally follows an autosomal recessive pattern of mendelian inheritance. The use of serum ferritin levels as a screen for this condition is reasonable. Cardiac magnetic resonance imaging (MRI) can be useful for the diagnosis of cardiac involvement. Hemochromatosis may result in a restrictive or dilated cardiomyopathy, with characteristic histologic features. Treatment is by repeated phlebotomy. Family screening is advised.

Sarcoidosis is a systemic disease resulting in the formation of noncaseating granulomas that can infiltrate the myocardium. It is associated with restrictive cardiomyopathy in 5% of patients, and may later progress to dilated cardiomyopathy. It is difficult to diagnose unless there is other organ involvement (usually pulmonary). It may be suspected in patients with cardiomyopathy and lymphadenopathy, skin rashes, or splenomegaly. Cardiac sarcoid is associated with ventricular tachycardia and conduction abnormalities (especially complete heart block) that can cause syncope and sudden cardiac death. EMB may show findings specific for sarcoidosis but, because of the patchy nature of the disease, biopsy may miss characteristic lesions, resulting in a low overall sensitivity. Cardiac granulomas may occasionally respond to steroids but turn to scar tissue. Sudden death is not prevented by steroids. Regular Holter monitoring is recommended to look for evidence of atrioventricular block, which should be treated with permanent pacemaker insertion or ventricular arrhythmias, which should be treated with an implantable cardioverterdefibrillator (ICD).

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Arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare but increasingly recognized condition characterized morphologically by apparent patchy apoptosis of the right and, to a lesser extent, left ventricles. It is sometimes called fat cardiomyopathy because of fatty infiltration of the right ventricle. It is familial in more than 50% of patients, generally with an autosomal dominant mode of inheritance.

Presentation is usually in early adulthood, with symptoms consistent with supraventricular and ventricular arrhythmias or with right-sided heart failure. It may be discovered during family screening. Often, sudden death is the first sign of ARVC, with the diagnosis made postmortem. EMB is associated with an increased risk of perforation and tamponade. Diagnostic features are summarized in Table 4 . Table 4: Diagnostic Features of Arrhythmogenic Right Ventricular Cardiomyopathy Diagnostic Modality Electrocardiography Features Epsilon waves (slurred ST segments) V1-3, inverted T waves V2, V3 * ) in absence of right bundle branch block Echocardiography Magnetic resonance imaging Histology
* In patients older than 12 years.

Localized RV aneurysm, isolated RV failure Fatty infiltration of right ventricle

Fatty infiltration of right ventricle

RV, right ventricular. 2003 The Cleveland Clinic Foundation.

Managing these patients is difficult and controversial. Control and prevention of potentially lethal ventricular arrhythmias are of paramount importance and have been approached with antiarrhythmic medications, radiofrequency ablation and, inevitably, ICDs. Control of right heart failure is difficult and sometimes impossible by conventional therapy. Cardiac transplantation provides effective therapy in select cases.

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Unclassified cardiomyopathies
Noncompacted myocardium manifests in early childhood. It appears to occur as a result of an arrest in endomyocardial morphogenesis. It is often associated with other cardiac abnormalities and extracardiac anomalies. Patchy preservation of the spongy morphology of the embryonic heart occurs, with persisting myocardial sinusoids and prominent ventricular trabeculations seen with echocardiography. It involves the right ventricle and may occasionally be biventricular. Clinical presentation includes ventricular arrhythmias, thromboembolism, and progressive systolic or diastolic heart failure, or both. It is a malignant condition with a high mortality. Death usually occurs in childhood. Patients are treated conventionally and some have successfully undergone heart transplantation. Systolic dysfunction with minimal dilation, as its name suggests, is characterized by systolic dysfunction, an ejection fraction lower than 30% (with no evidence of restrictive physiology by definition), and preserved left ventricular

dimensions. Histologically, there is little myofibrillar loss. It carries a poor prognosis. Patients are treated with conventional approaches. A family history of dilated cardiomyopathy is not uncommon. Mitochondrial cardiomyopathy, arising from mutations in mitochondrial DNA, with resultant impaired oxidative phosphorylation, is transmitted through the maternal line. The resultant cardiomyopathy is characterized by progressive hypertrophy, dilation, and arrhythmias. Mitochondrial diseases generally are systemic, in tissues with high metabolic activity, and give rise to syndromes. The MELAS syndrome ( m itochondrial e ncephalopathy, l actic a cidosis, and strokelike syndrome) can manifest as cardiomyopathy. When a mitochondrial myopathy is suspected, electron microscopy of EMB specimens may reveal giant mitochondria, concentric cristae, and intramitochondrial inclusions. However, skeletal muscle biopsy should be considered first, because it is a safer alternative. Endocardialfibroelastosis is a rare condition that usually manifests in infancy or early childhood. It is characterized by thickening of the left ventricle and left-sided cardiac valves. Multiple modes of inheritance have been described. Dilated or restrictive cardiomyopathy can result.
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General considerations
Signs and Symptoms
The cardiomyopathies represent a spectrum of disease and as such have various presentations (Fig. 1). Patients may remain asymptomatic and are diagnosed only by screening or postmortem examination. They may present with symptoms of heart failure (see elsewhere in this section, Heart Failure), chest pain, or dysrhythmias. The clinical course may fluctuate. Unfortunately, the most common clinical presentation is one of progressive deterioration, with worsening heart failure and death occurring over a variable time course.

Figure 1: Click to Enlarge

A careful history is essential, with particular emphasis on family history. A family tree should be constructed to ascertain whether a pedigree exists that is consistent with familial cardiomyopathy. This may necessitate requesting autopsy reports and medical records, because a high index of suspicion is required. Additional features in the history

should focus on exposure to cardiotoxins such as alcohol or cocaine. Specific interrogation about a protracted flulike illness or respiratory tract infection may suggest previous myocarditis. Key points to assess in patients with known or suspected cardiomyopathy are as follows: 1. Establishing the onset and severity of symptoms of dyspnea, fatigue, fluid retention, and effect on activities of daily living 2. Conventional risk factors for vascular disease (e.g., smoking, hypertension, diabetes, hyperlipidemia) or prior cardiac events (e.g., myocardial infarction, coronary artery bypass grafting) 3. 4. 5. Family history of heart disease, especially sudden death Alcohol, amphetamine, cocaine use Any past or current major medical illness

The use of genetic screening in the management of cardiomyopathy currently is under evaluation in many centers, but has not yet proven to be clinically useful. Screening first-degree relatives of patients with known or suspected familial cardiomyopathy is currently best achieved by physical examination, ECG, and echocardiography. The age at which screening should commence and how often it should be continued are unclear. Examination should focus on whether the heart is palpably dilated, the presence of murmurs, and additional heart sounds (gallops). It is important to look beyond the cardiovascular system to consider a possible systemic disorder that may be contributory or causal, such as hemochromatosis or thyrotoxicosis. There are five useful clinical signs to establish the presence and severity of cardiomyopathy: (1) general appearancecachexia and dyspnea at rest indicate severe impairment; (2) hypotension; (3) tachycardia; (4) elevated jugular venous pressure; and (5) displaced left ventricular point of maximal impulse (PMI). Basic investigations should include a chest radiograph, ECG, and echocardiogram. Screening laboratory investigations include a complete blood cell count and renal, glucose, lipid, liver, and thyroid panels. It is reasonable to measure ferritin levels if hemochromatosis is suspected. The usefulness of viral titers has not been proven, although it may be reasonable to perform specific viral serology, such as for HIV if indicated by the history. BNP has been identified as a useful marker for the diagnosis, severity, and prognosis in patients with heart failure. BNP levels correlate with functional class but not with ejection fraction. The five most common abnormalities seen on the ECG are (1) Q waves (from a previous myocardial infarction), (2) diffuse ST-segment abnormalities, (3) left bundle branch block (or any intraventricular conduction delay), (4) atrial fibrillation, and (5) abnormal P waves (biphasic in leads V1 and V2left atrial overload). Figure 2 shows intraventricular delay and diffuse ST-segment abnormalities in an ECG from a patient with dilated

cardiomyopathy. Figure 3 shows atrial fibrillation, poor R wave progression, and diffuse ST-segment abnormalities in an ECG from a patient with ischemic cardiomyopathy.

Figure 3: Click to Enlarge

Figure 2: Click to Enlarge Common abnormalities seen on the chest radiograph include cardiomegaly, interstitial edema, pleural effusion(s), and evidence of previous sternotomy (sternal wires). Common abnormalities seen on the echocardiogram include increased chamber dimensions, reduced fractional shortening or ejection fraction, functional mitral and tricuspid valvular regurgitation, regional wall motion abnormalities, and myocardial thickening (hypertrophy or infiltration). Common abnormalities seen on Holter monitoring include premature ventricular complexes, premature atrial complexes, atrial fibrillation (either sustained or paroxysmal), nonsustained ventricular tachycardia, and first- or second-degree atrioventricular block. It is important to rule out ischemia as a cause of ventricular dysfunction. This can most definitively be determined by cardiac catheterization and coronary arteriography. Noninvasive modalities such as dobutamine stress echocardiography and nuclear stress testing are available at most centers as screening tests for coronary artery disease. Positron emission tomography and MRI are other noninvasive modalities that are only available at large centers.

Role of Endomyocardial Biopsy in the Diagnosis of Cardiomyopathy

2 EMB is not indicated in the routine evaluation of cardiomyo-pathy, even though it has a complication rate of lower

than 1%.15 Most histologic specimens demonstrate nonspecific changes of myocyte hypertrophy, cell loss, and fibrosis (Fig. 4) and do not affect medical management. Histologically specific changes do occur in sarcoid (although they are patchy, reducing sensitivity), amyloid, hemochromatosis (Fig. 5), endocardialfibroelastosis, Lffler's endocarditis, and ARVC (Fig. 6). These conditions may be diagnosed with other less invasive tests. In addition, there are no data proving that treatment improves outcome in cardiac sarcoid or amyloid, although some would support the use of EMB in suspected cases of amyloid to establish the diagnosis and predict a poor prognosis (mean survival, 6

to 12 months). Because of recurrent disease, cardiac amyloid generally renders the patient ineligible for cardiac transplantation.

Figure 5: Click to Enlarge

Figure 4: Click to Enlarge EMB in acute myocarditis is not useful because aggressive immunosuppressive regimens, once believed to be efficacious, do not appear to improve outcome. However, the one exception is that giant cell myocarditis, suggested by a rapidly progressive and downhill course, may benefit from aggressive therapy (e.g., intensive hemodynamically guided heart failure therapy, immunosuppression, left ventricular assist device, transplantation). In addition to its use for potential giant cell myocarditis, EMB, combined with cardiac imaging techniques, may be used to document anthracycline toxicity, although BNP levels may be a more sensitive marker.

Figure 6: Click to Enlarge EMB is sometimes useful for distinguishing constrictive from restrictive pathology (the latter being associated with infiltration on EMB). 16 However, this distinction can generally be made with the use of a number of imaging techniques, including echocardiography with diastolic studies (see elsewhere in this section, Pericardial Disease), MRI, computed tomography, and cardiac catheterization.

Treatment and Outcomes of Cardiomyopathies

Therapy for cardiomyopathy generally is the same as for heart failure. However, the usefulness of therapies for specific populations remains to be defined, including those for patients with asymptomatic left ventricular dilation. Neither steroids nor intravenous immunoglobulin are useful in the management of cardiomyopathy. In the absence of a specific remediable cause (e.g., peripartum, alcoholic, ischemic, or hibernating cardiomyopathy), the overall outcome is poor. The 5-year survival rate of patients diagnosed with heart failure is 50%. 17 This is paralleled by a high morbidity, characterized by polypharmacy and multiple hospital admissions. Several clinical and laboratory features imply a poor prognosis ( Table 5 ).

Table 5: Predictors of Poor Outcome in Dilated Cardiomyopathy Test Clinical findings Features Increased age, male gender, ischemic heart disease, diabetes, syncope, right heart failure symptoms, symptomatic ventricular arrhythmias, persistent gallop rhythm, persistent jugular venous distention, systemic hypotension, peripheral vascular disease Laboratory findings Hyponatremia, persistently elevated B-type natriuretic peptide and A-type natriuretic peptide levels, elevated norepinephrine and renin levels Electrocardiography Echocardiography Left bundle branch block, first- and second-degree atrioventricular blocks Increased ventricular dimensions, reduced ejection fraction, restrictive diastolic filling pattern, severe mitral or tricuspid regurgitation, or both Chest radiography Coronary angiography Hemodynamic data Increased cardiothoracic ratio Multivessel obstructive disease Pulmonary capillary wedge pressure >20 mm Hg, cardiac index <2.5 L/min/m , pulmonary hypertension, elevated central venous pressure Cardiopulmonary exercise test Endomyocardial biopsy
Data from: Topol E: Textbook of Cardiovascular Medicine. Philadelphia: Lippincott Williams & Wilkins, 2002; Bart BA, Shaw LK, McCants CB, Jr., et al: Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. J Am CollCardiol 1997;30:1002-1008; and Koelling TM, Aaronson KD, Cody RJ, et al: Prognostic significance of mitral regurgitation and tricuspid regurgitation in patients with left ventricular systolic dysfunction. Am Heart J 2002;144:524-529.

Maximal systemic oxygen uptake <12 mL/kg/min

Loss of intracellular myofilaments

Metabolic stress testing is useful to gauge effort tolerance objectively, and a peak V.o2 uptake of lower than 14 mL/kg/min is generally accepted as a criterion for heart transplantation. Heart transplantation provides a median survival of 12 years and is effective palliation for appropriately selected individuals. Which patients should I refer to a cardiologist? Because of the poor prognosis in most cases of cardiomyopathy, all patients for whom active treatment is contemplated should be referred to a cardiologist to ascertain the cause so that an aggressive, tailored treatment plan can then be initiated.

Cardiomyopathies are diseases of the myocardium associated with cardiac dysfunction, often resulting in the clinical syndrome of heart failure.

Dilated cardiomyopathy is defined as an ejection fraction of lower than 40% in the presence of increased left ventricular dimensions. There are a number of possible causes.

Restrictive cardiomyopathy is a disease of the myocardium, characterized by restrictive filling and reduced diastolic volume of the ventricles, with normal or near-normal systolic function.

Cardiomyopathies are diagnosed by history, physical examination, ECG, chest x-ray, echocardiogram and, in some cases, endomyocardial biopsy.

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1. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation. 93: 1996; 841-842. 2. American College of Cardiology; American Heart Association Task Force on Practice Guidelines; American College of Chest Physicians; International Society for Heart and Lung Transplantation; Heart Rhythm Society. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society. Circulation. 112: 2005; e154-e235. 3. 4. 5. Ventricular remodeling. Mechanisms and prevention. CardiolClin. 16: 1998; 623-632. Myocarditis: Current trends in diagnosis and treatment. Circulation. 113: 2006; 876-890. Familial dilated cardiomyopathy: From clinical presentation to molecular genetics. Eur Heart J. 21: 2000; 1825-1832. 6. Alcoholic cardiomyopathy: Incidence, clinical characteristics, and pathophysiology. Chest. 121: 2002; 16381650.

7. 8.

Cardiovascular complications of cocaine use. N Engl J Med. 345: 2001; 1575-1576. Cardiovascular complications of cancer therapy: Diagnosis, pathogenesis, and management. Circulation. 2004; 3122-3131.


Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy. N Engl J Med. 344: 2001; 1567-1571.

10. Textbook of Cardiovascular Medicine. 2002; ;Philadelphia. 11. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 342: 2000; 1077-1084. 12. Safety and efficacy of recombinant human alpha-galactosidaseA replacement therapy in Fabry's disease. N Engl J Med. 345: 2001; 9-16. 13. Diagnosis and management of the cardiac amyloidoses. Circulation. 112: 2005; 2047-2060. 14. Arrhythmogenic right ventricular cardiomyopathy/dysplasia: Clinical impact of molecular genetic studies. Circulation. 113: 2006; 1634-1637. 15. Current role of endomyocardial biopsy in the management of dilated cardiomyopathy and myocarditis. Mayo Clin Proc. 76: 2001; 1030-1038. 16. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J. 22: 2001; 1527-1560. 17. Long-term trends in the incidence of and survival with heart failure. N Engl J Med. 347: 2002; 1397-1402. 18. Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. J Am CollCardiol. 30: 1997; 1002-1008. 19. Prognostic significance of mitral regurgitation and tricuspid regurgitation in patients with left ventricular systolic dysfunction. Am Heart J. 144: 2002; 524-529.

Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium (i.e., the actual heart muscle) for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both.

Although in theory the term "cardiomyopathy" could apply to almost any disease affecting the heart, in practice it is usually reserved for "severe myocardial disease leading to heart failure".

Cardiomyopathies can be categorized as extrinsic or intrinsic.[3]  An extrinsic cardiomyopathy is a cardiomyopathy where the primary pathology is outside the myocardium itself. Most cardiomyopathies are extrinsic, because by far the most common cause of a cardiomyopathy is ischemia. The World Health Organization calls thesespecific cardiomyopathies:

An intrinsic cardiomyopathy is defined as weakness in the muscle of the heart that is not due to an identifiable external cause. This definition was used to categorize previously idiopathic cardiomyopathies although specific external causes have since been identified for many. For example, alcoholism has been identified as a cause for some forms of dilated cardiomyopathy. To make a diagnosis of an intrinsic cardiomyopathy, significant coronary artery disease should be ruled out (amongst other things). The term intrinsic cardiomyopathy does not describe the specific etiology of weakened heart muscle. The intrinsic cardiomyopathies consist of a variety of disease states, each with their own causes. Many intrinsic cardiomyopathies now have identifiable external causes including drug and alcoholtoxicity, certain infections (including Hepatitis C), and various genetic and idiopathic (i.e., unknown) causes.

It is also possible to classify cardiomyopathies functionally, as involving dilation, hypertrophy, or restriction.[4] [edit]Types

Primary/intrinsic cardiomyopathies  Genetic      Hypertrophic cardiomyopathy (HCM or HOCM) Arrhythmogenic right ventricular cardiomyopathy (ARVC) Isolated ventricular non-compaction Mitochondrial myopathy

Mixed   Dilated cardiomyopathy (DCM) Restrictive cardiomyopathy (RCM)

Acquired   Takotsubo cardiomyopathy Loeffler endocarditis

Secondary/extrinsic cardiomyopathies  Metabolic/storage    amyloidosis hemochromatosis

Inflammatory  Chagas disease[5][6]



diabetic cardiomyopathy hyperthyroidism

Toxicity   chemotherapy Alcoholic cardiomyopathy

Neuromuscular  muscular dystrophy


Nutritional diseases Other  "Ischemic cardiomyopathy" is a weakness in the muscle of the heart due to inadequate oxygen delivery to the myocardium with coronary artery disease being the most common cause. Not supported by current cardiomyopathies classification schemes. [edit]Signs

and symptoms

Symptoms and signs may mimic those of almost any form of heart disease. Chest pain is common. Mild myocarditis or cardiomyopathy is frequently asymptomatic; severe cases are associated with heart failure, arrhythmias, and systemic embolization. Manifestations of the underlying disease (e.g., Chagas' disease) may be prominent. Most patients with biopsy-proven myocarditis report a recent viral prodrome preceding cardiovascular symptoms. ECG abnormalities are often present, although the changes are frequently nonspecific. A pattern characteristic of left ventricular hypertrophy may be present. Flat or inverted T waves are most common, often with low-voltage QRS complexes. Intraventricular conduction defects and bundle branch block, especially left bundle branch block, are also common. An echocardiogram is useful to detect wall motion abnormalities or a pericardial effusion. Chest radiographs can be normal or can show evidence of congestive heart failure with pulmonary edema or cardiomegaly. [edit]Treatment Treatment depends on the type of cardiomyopathy, but may include medication, implanted pacemakers, defibrillators, or ventricular assist devices (LVADs), or ablation. The goal of treatment is often symptom relief, and some patients may eventually require a heart transplant. Treatment of cardiomyopathy (and other heart diseases) using alternative methods such as stem cell therapy is commercially available but is not supported by convincing evidence.