Cardiomyopathies Case File
Eugene C. Toy, Md, Michael d . Faulx, Md
Case 18
A 63-year-old man comes to visit you because of multiple recent hospital admissions for shortness of breath and recurrent pleural effusions necessitating thoracenteses. The patient describes 3 months of worsening dyspnea on exertion and frequent palpitations. He cannot climb one flight of stairs because of dyspnea and sleeps on three pillows because he becomes dyspneic while lying flat. On review of systems (RoS) he reports frequent lightheadedness, an unintentional 15-lb weight loss, and loss of sensation in his feet with a “pins and needles” feeling. He denies chest pain or syncope. He has no known cardiac disease and previously considered himself healthy. He is a lifelong nonsmoker who drinks two glasses of wine each week with dinner. He has no family history of coronary heart disease, but his father had atrial fibrillation and developed heart failure in his late 50s. On examination the patient is nondistressed and thin. Vital signs are as follows: blood pressure 108/ 64 mmHg (right arm, sitting), 106/ 64 mmHg (left arm, sitting), and 92/58 mmHg (right arm, standing); carotid pulse was 63 bpm and regular; body mass index (BMI) 21 kg/m2; and jugular venous pressure (JVP) is triphasic and 14 cm H2O. He has a large tongue and small bruises near his eyelids. There is no thyromegaly or palpable lymphadenopathy. Cardiac examination reveals a laterally displaced and diffuse point of maximal impulse (PMI). There is an S4 gallop without murmurs on auscultation. He has dullness to percussion and diminished breath sounds on auscultation at the lung bases. The abdominal examination was normal. All remaining pulses were brisk and symmetric. His extremities are cool and noncyanotic with pitting edema to his midshin. He has diminished sensation to pinprick on his toes and fingertips. He brings an electrocardiogram (ECG) from his previous hospital admission (Figure 18-1).
- What is the most likely diagnosis?
- What is the best next diagnostic step?
- What is the best treatment for this patient?
Figure 18-1. ECG for main subject of this case.
Answer to Case 18:
Cardiomyopathies
Summary: A 63-year-old man is currently being seen in your office for evaluation a history of recurrent pleural effusions, weight loss, palpitations, and neuropathy. He notes that his father had a history of atrial fibrillation and heart failure in his 50s. He explains to you that he is having exertional dyspnea and orthopnea. He denies any angina or syncope but does admit to some positional lightheadedness. He does not smoke and rarely drinks alcohol. He appears thin and has some bruising around his eyelids and a large tongue. His jugular venous pressure is elevated, his PMI is laterally displaced and diffuse, and he has an S4 gallop. He has dullness to percussion and diminished breath sounds at his lung bases with peripheral edema and diminished sensation on neurological examination. His ECG is notable for low limb voltages, atrial enlargement, and left ventricular hypertrophy.
- Most likely diagnosis: Amyloidosis with cardiac involvement, possible familial.
- Next diagnostic step: Transthoracic echocardiography.
- Best treatment: Start the patient on loop diuretic.
ANALYSIS
Objectives
- Know the breadth and diversity of cardiomyopathy pathology.
- Comprehend the management of and treatment decisions for the various types of cardiomyopathy.
- Recognize the importance of family history on cardiomyopathy.
Considerations
This is a 63-year-old man with 3 months of recurrent pleural effusions, palpitations, dyspnea on exertion, orthopnea, weight loss, and neuropathy. He has a family history of atrial fibrillation and “heart failure” in his father and physical findings suggestive of decreased weight, pleural effusions, and volume excess. His ECG is consistent with amyloidosis infiltrative cardiomyopathy. The differential diagnosis includes light-chain amyloidosis, hereditary (transthyretin mutant) amyloidosis, senile amyloidosis, or other infiltrative cardiomyopathy. However, given his father’s history of heart failure, hereditary amyloidosis warrants strong diagnostic consideration. In addition to a transthoracic echocardiogram, his workup must include assessment for renal function, complete blood count, and urine and protein electrophoreses to look for any plasma cell dyscrasias. In addition, a tissue diagnosis is essential. Endomyocardial biopsy often reveals amyloid amorphous light pink material interspersed within darker myocytes on hematoxylin and eosin staining. These infiltrates often stain positive with thioflavin S. Additional immunohistochemical staining for transthyretin and kappa and lambda chains will narrow the diagnosis.
He is currently in decompensated heart failure as evidenced by his elevated jugular venous pressures and peripheral edema and warrants diuresis with a loop diuretic. Avoid calcium channel blockers, beta-blockers, digoxin, or other atrioventricular nodal blocking agents as they are poorly tolerated in patients with amyloid heart disease and may worsen hypotension. Pending the above-mentioned workup, consider pathologic diagnosis via endomyocardial biopsy. Furthermore, he is at risk for developing atrial arrhythmias such as atrial flutter and atrial fibrillation and warrants ambulatory monitoring. Should the results of his biopsy suggest hereditary amyloidosis, he should be counseled to undergo genetic testing.
Approach To:
Cardiomyopathies
DEFINITIONS
CARDIOMYOPATHY: Any pathology of the heart muscle that results in a decline of function of the myocardium that typically leads to a heart failure syndrome. Patients with cardiomyopathies may experience edema, ascites, dyspnea, arrhythmias, or even sudden cardiac death. Cardiomyopathies can be coarsely divided into two classes: those attributable to coronary heart disease (ischemic cardiomyopathy, ICM) and those that are not related to ischemic heart disease (nonischemic cardiomyopathy, NICM).
CLINICAL APPROACH
Initial Evaluation of the Patient With Cardiomyopathy
Given the considerable diversity of cardiomyopathy pathology, taking a thorough and accurate history and family history in addition to physical examination is essential. Certain physical findings, family histories, or exposures can provide strong clues pointing to the specific etiology. However, despite a thorough evaluation, most cardiomyopathy etiologies are idiopathic.
When considering the diagnosis of cardiomyopathy, it is first essential to consider the two main categories of cardiomyopathy: primary cardiomyopathies, which are caused by an intrinsic myocardial disorder, or secondary cardiomyopathies, which are caused by extrinsic conditions (Figures 18-2 and 18-3). By far, ischemic cardiomyopathy is both the most prevalent and incident form of secondary cardiomyopathy. Primary cardiomyopathies, however, may have specific external causes. In order to make the diagnosis of a primary cardiomyopathy, obstructive coronary heart disease must be ruled out. These cardiomyopathies include diverse disease states, each with its own etiology.
Primary Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is histologically characterized by disordered myocyte growth and fibrosis. Wall thickening typically involves the septum and less commonly, the apex of the heart. HCM is the most common genetically
Figure 18-2. Primary cardiomyopathies (HCM, hypertrophic cardiomyopathy ).
mediated cardiovascular disease and is the most prevalent cause of death in young athletes. Symptoms include dyspnea on exertion, fatigue, and lightheadedness, and are usually related to conditions that affect the dynamic left ventricular outflow tract (LVOT) obstruction and increase diastolic pressures. Activities that produce elevated heart rates and decreased preload will worsen LVOT obstruction and cause symptoms. [When there is significant LVOT obstruction, this condition may be referred to as hypertrophic obstructive cardiomyopathy (HOCM).] HCM is a significant risk factor for sudden cardiac death. The murmur of HCM is classically described as a harsh, crescendo-decrescendo murmur heard best at the left
Figure 18-3. Secondary cardiomyopathies (CMV, cytomegalovirus; HIV, human immunodeficiency virus).
intercostal space that augments with the Valsalva maneuver and standing–conditions that decrease preload. Treatment consists of atrioventricular nodal blocking agents that prolong LV filling time. Most commonly, beta-blockers are the drugs of choice. Patients with HCM (hypertrophic cardiomyopathy) may need ICDs, and definitive treatment involves either surgical or percutaneous septal reduction therapy. For more information regarding HCM, please refer to Case 8.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is another form of genetically mediated cardiomyopathy whereby mutations in desmosomes in the right ventricular myocardium cause an excess of fibrous and fatty tissue in place of normal muscle. It typically begins in the right ventricle, leading to dilatation and RV failure, and may extend well into the left ventricle. Patients with this rare disorder typically present with heart failure, arrhythmia, and sudden cardiac death. An early manifestation of ARVC may be ventricular tachycardia (VT) originating from the right ventricle. Increased levels of myocardial involvement typically correlate with an increased risk of VT and ICDs are often the only available therapy to curtail the risk of sudden cardiac death. Exercise and vigorous physical activity are typically contraindicated as they may provoke the arrhythmias.
Dilated cardiomyopathies (DCMs) are the most common form of nonischemic cardiomyopathy. DCM is typically characterized by a dilated hypertrophied ventricle not due to any identifiable cause. Some developments of DCM are often assumed to be related to remote episodes of viral myocarditis due to Coxsackie B or other enteroviruses. However, 25–35% of DCMs are familial, with mutations affecting the cardiomyocyte cytoskeleton or the cardiomyocyte contraction mechanism. However, only 15–25% of familial DCMs have a detectable genetic mutation. DCM is more common in males than females and typically carries a more favorable prognosis than ischemic cardiomyopathy.
Peripartum cardiomyopathy is a rare form of DCM that typically develops in a timeframe that lasts from the final month of pregnancy until 5 months into the postpartum period. Although most patients with peripartum cardiomyopathy improve with medical therapy, nearly a third of all patients develop worsening heart failure. The cause of peripartum cardiomyopathy is unknown and likely involves a triggered inflammatory process. If, after months to a year, the left ventricular ejection fraction does not recover, the risk of heart failure during a subsequent pregnancy increases to nearly 21%.
Takotsubo cardiomyopathy, or stress-induced cardiomyopathy or apical ballooning syndrome, is a disease entity affecting primarily postmenopausal women. This weakening of the myocardium can be caused by emotional stress such as a sudden relationship breakup, death of a loved one, or severe anxiety. It is thus commonly also called “broken heart syndrome.” Takotsubo cardiomyopathy commonly presents in a manner identical to that of an anterior wall myocardial infarction with chest pain, dyspnea, anterior ST segment elevation, and elevated cardiac biomarkers. Coronary angiography is often normal or reveals mild angiographic disease. The classic finding in Takotsubo cardiomyopathy is ballooning or marked dyskinesis of the left ventricular apex with hyperkinesis of the basal segments (Figure 18-4). The apical ballooning can be seen on ventriculography or echocardiography and it is transient; often there is dramatic improvement in systolic function within 48 hours
of presentation. A supraphysiological catecholamine surge is believed to cause this syndrome. Although patients may be dramatically ill on presentation, most patients with Takotsubo’s cardiomyopathy improve within 6 months, and the overall prognosis is quite good.
Secondary Cardiomyopathy
By far, the most prevalent and incident form of either secondary cardiomyopathy is ischemic cardiomyopathy (ICM). Because it is essential to rule out significant coronary heart disease, diagnostic coronary angiography is an essential component of the evaluation of a patient with a newly diagnosed cardiomyopathy. ICM represents nearly 60–75% of all cases of systolic heart failure in industrialized countries and is typically defined as cardiomyopathy in the presence of extensive postmyocardial infarction scar, ischemia, or severely obstructive coronary heart disease. Once the diagnosis is highly suspected, it is essential to provide a thorough assessment regarding the risks and the benefits of either percutaneous or surgical revascularization.
Cardiotoxic agents can typically cause cardiomyopathy. Anthracyclines, cyclophosphamide, and trastuzumab are cancer chemotherapeutic agents associated with cardiomyopathy. Anthracycline chemotherapeutics such as doxorubicin commonly cause cardiomyocyte destruction. Although the highest lifetime risk of developing cardiomyopathy from this drug is near 20% for those receiving a cumulative dose of > 700 mg/m2, most patients who receive <400 mg/m2 are at a much lower lifetime risk.
Alcohol consumption is a well-known common cause of cardiomyopathy. However, little is known about the amount or duration of alcohol necessary to cause the cardiomyopathy. Once cardiomyopathy is diagnosed, continued alcohol use may confer a 50% 3–6-year mortality, but abstinence may resolve the cardiomyopathy.
Stimulant drugs of abuse may also cause cardiomyopathy. Classic examples are cocaine and amphetamines. Stimulant drug abuse adversely affects the heart in several ways, but the most common pathologic observation is the development of concentric ventricular hypertrophy followed by progressive systolic dysfunction or an ischemic pattern of cardiomyopathy due to recurrent drug-induced myocardial infarctions.
Severe valvular heart disease commonly leads to the development of systolic dysfunction. Both aortic insufficiency and mitral insufficiency can lead to the development of cardiomyopathy via chronic pressure and volume overload leading to dilatation of the left ventricle. Additionally, severe aortic stenosis and left ventricular (LV) outflow obstruction can lead to progressive LV dysfunction over time. The ultimate therapy for these cardiomyopathies is surgical, although recovery of LV systolic function is more predictable after correction of pure pressure overload states (severe aortic stenosis) versus pure volume overload states (severe aortic or mitral regurgitation).
Chronic hypertension can lead to the development of either LV diastolic dysfunction or systolic function. The development of LV hypertrophy (LVH) commonly precedes the development of either systolic dysfunction via thinning and eventual dilation of the myocardium or diastolic dysfunction. Uncommonly, patients with hypertension may skip the development of LVH and proceed directly to systolic dysfunction. Hypertension is also a classic risk factor for coronary heart disease and may lead to the development of ischemic cardiomyopathy.
Diabetes mellitus is a well-described risk factor for obstructive coronary artery disease, and it promotes the development of ischemic cardiomyopathy as well. However, diabetes may lead to the development of cardiomyopathy via a mechanism that is independent of coronary artery disease. Perturbations in free fatty acid and glucose metabolism in the myocardium may lead to abnormal accumulation of free fatty acids in the myocardium in addition to alterations in peroxisome-proliferator-activated receptor alpha function. The benefits of intensive glucose control are unclear, and it may even be harmful. Administration of metformin, a biguanide that decreases gluconeogenesis in the liver, may decrease the risk for developing cardiomyopathy.
Patients with longstanding, poorly controlled tachycardia with heart rates of >110 bpm may develop tachycardia-induced cardiomyopathy. Atrial fibrillation, atrial flutter, atrial tachycardia, and even ventricular arrhythmia may cause this entity. Identifying this diagnosis is essential, as the resolution of arrhythmia may reverse ventricular dysfunction.
Thyroid disorders can commonly lead to the development of cardiomyopathy. Severe hypothyroidism, or myxedema, may cause cardiomyocyte hypertrophy and dilation and lead to the development of decreased cardiac output and heart failure. Hyperthyroidism may lead to the development of cardiomyopathy by causing atrial fibrillation or high-output heart failure. Because reversal of this endocrinopathy can lead to the reversal of cardiomyopathy, measuring thyroid-stimulating hormone levels and–if suspicion is high–thyroxine levels, is critical in anyone presenting with a cardiomyopathy.
Nutritional and vitamin deficiencies, although very rare in developed parts of the globe, can lead to the development of ventricular dysfunction. Thiamine deficiency (beriberi) can lead to a syndrome of high-output heart failure characterized by marked edema, pulmonary congestion, and peripheral vasodilation. Thiamine deficiency characterized by cardiomyopathy is typically referred to as “wet” beriberi. Diagnosis is established by decreased erythrocyte transketolase and low 24-urine thiamine levels. Treatment with intravenous thiamine followed by oral thiamine supplementation can lead to resolution of this cardiomyopathy. Rarely, in patients on chronic parenteral nutrition, carnitine and selenium deficiencies may cause cardiomyopathy.
Both primary and secondary hemachromatoses may lead to a restrictive cardiomyopathy via chronic stiffening of the ventricle from iron deposition. The myocardium may stretch, and the ventricle can dilate over time, leading to systolic dysfunction as well. Although treatment with iron-chelating agents or phlebotomy may improve myocardial function, the deposition may become so severe that these therapies may have little effect.
Genetic skeletal myopathies such as Duchenne’s, Becker’s, and limb girdle muscular dystrophy can involve the myocardium and lead to the development of DCM.
Systemic sarcoidosis can involve the heart. Inflammation from sarcoidosis can lead to the development of varying degrees of heart block and to ventricular arrhythmia and LV dysfunction. Although the presence of noncaseating granulomas on endomyocardial biopsy is the gold standard for establishing this diagnosis, these granulomas are rarely seen. As such, this diagnosis is typically made through either cardiac MRI or positron emission tomography (PET). If there is radiographic evidence of active inflammation, immunosuppressives are commonly used.
In 20–50% of subjects infected by the protozoan Trypanosoma cruzi, chronic Chagas disease may involve the myocardium. In the chronic phase this causes a DCM in the absence of significant obstructive coronary artery disease. Patients with this disorder are commonly from Latin America. High T. cruzi titers can facilitate diagnosis.
CASE CORRELATION
- See also Case 16 (acute heart failure) and Case 17 (advanced heart failure).
COMPREHENSION QUESTIONS
18.1 Which of the following cardiomyopathies can be definitively managed surgically?
A. Sarcoid cardiomyopathy
B. Chagas cardiomyopathy
C. Valvular cardiomyopathy
D. Amyloid cardiomyopathy
E. Dilated cardiomyopathy
18.2 A 42-year-old African American man presents with dyspnea on exertion and episodes of lightheadedness. He has no family history of cardiomyopathy. On examination he is normotensive, is bradycardic, and has a diffuse and laterally displaced PMI. His jugular venous pulse is at 7 cm of water, and he has dry rales throughout his lung fields without any peripheral edema. On ECG he is in first-degree atrioventricular block. What is the most likely diagnosis?
A. Ischemic cardiomyopathy
B. Amyloid cardiomyopathy
C. Sarcoid cardiomyopathy
D. Hypertensive cardiomyopathy
E. Carnitine cardiomyopathy
18.3 A 60-year-old woman presents to the emergency department complaining of dyspnea on exertion and orthopnea. She tells you that she took medication but stopped nearly 2 months ago. She complains of low energy, weight gain, cold intolerance, and thinning hair. On examination her blood pressure is 140/106 mmHg, and her pulse is regular at 58 bpm with peripheral edema and cool extremities. She has a laterally displaced and diffuse PMI, and her JVP is 10 cm of water. Her LV ejection fraction is 35%. Which of the following lab studies would reveal the most likely etiology of her cardiomyopathy?
A. Thyroid-stimulating hormone (TSH)
B. Ferritin
C. Troponin T
D. Urinary thiamine
E. Hemoglobin A1C
ANSWERS
18.1 C. The definitive management for most valvular cardiomyopathies is surgical repair or replacement of either the regurgitant or the stenotic valve.
18.2 C. This patient has physical examination findings consistent with both cardiomyopathy and noncardiac lung disease. He has ECG evidence of abnormal AV nodal conduction. Given this constellation of findings in addition to his race, the most likely diagnosis is sarcoid cardiomyopathy.
18.3 A. This woman’s physical findings are consistent with clinical hypothyroidism. Additionally, the medication she is no longer taking was likely thyroid replacement hormone. Now she presents with a cardiomyopathy and checking a TSH level would likely confirm the diagnosis.
CLINICAL PEARLS
- The most common cause of cardiomyopathy is ischemic; therefore, diagnostic coronary angiography should be considered in every newly diagnosed cardiomyopathy.
- A thorough past medical history, family history, physical examination, and appropriate laboratory evaluation should be undertaken in order to help diagnose that etiology of cardiomyopathy and to look for treatable causes.
- Most cases of nonischemic cardiomyopathy are idiopathic.
- HCM is often hereditary.
References
Grodin JL, Tang WH. Treatment strategies for the prevention of heart failure. Curr Heart Fail Rep. 2013;10(4):331–340.
Hershberger RE, Siegfried JD. Update 2011: clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol. 2011;57(16):1641–1649.
Hunt SA. 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). J Am Coll Cardiol. 2005;46(6):e1–e82.
Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):1977–2016.
Nishimura RA, Holmes DR Jr. Clinical practice. Hypertrophic obstructive cardiomyopathy. N Engl J Med. 2004;350(13):1320–1327.
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