1. Answer: B. Selenium, thiamine, and carnitine deficiencies are all associated with the development of a reversible cardiomyopathy that responds to repletion of the deficient vitamin/mineral. Folate and B12 deficiency are not usually associated with cardiomyopathy. Thiamine deficiency or beriberi is usually seen in alcoholic patients with poor nutrition and produces a clinical syndrome that is characterized by high-output cardiac failure. Selenium deficiency, also called Keshan disease, is usually seen in patients undergoing total parenteral nutrition or in patients from areas where food is grown in selenium-deficient soil and results in cardiac enlargement and systolic heart failure. Carnitine deficiency may be primarily due to a genetic defect or secondary as a result of total parenteral nutrition or liver or renal disease. Carnitine is required for normal energy metabolism and contractile function in the heart and its deficiency can result in systolic impairment.

The description of a homeless man with a low body mass index and cardiomyopathy is suspicious for nutritional deficiency as a potential etiology. The Doppler variables shown in this question can be used to calculate the cardiac output and index. Cardiac output = stroke volume (cross-sectional area × left ventricular outflow tract time velocity integral [LVOT TVI]) × heart rate = 3.14 × (LVOT diameter)²/4 × 36 × 86 = 11.8 L/min. Cardiac index = cardiac output/body surface area = 6.2 L/min/m². Although selenium and carnitine deficiency can also cause cardiomyopathy, only thiamine deficiency causes high cardiac output failure. The correct answer is therefore (B) thiamine deficiency.

2. Answer: A. Hereditary hemochromatosis is an autosomal recessive iron-storage disease associated with mutations in the HLA-linked HFE gene and is seen almost entirely in people of northern European descent. There is accumulation of iron in the heart, liver, pancreas, skin, and gonads. When cardiac involvement is present, the disease is usually in the advanced stage with multiorgan involvement (diabetes, cirrhosis, arthritis, and impotence). The severity of myocardial dysfunction is proportional to the extent of myocardial iron deposition. Cardiac manifestations include congestive heart failure, arrhythmias, and conduction abnormalities.

Echocardiographic findings usually consist of mild LV dilatation, LV systolic dysfunction, normal or mildly increased wall thickness, relatively normal cardiac valves, and biatrial enlargement. The LV diastolic filling pattern is usually restrictive and morphologic two-dimensional echocardiographic features are essentially those of dilated cardiomyopathy.

The correct answer is (A) dilated left ventricle and systolic dysfunction. LV wall thickness may be mildly increased but is frequently normal. Regional wall motion abnormalities are not typically present. Although secondary pulmonary hypertension may be present due to restrictive LV physiology, this is not a prominent finding. Pericardial effusion is not typical.

3. Answer: B. Selenium deficiency, also called Keshan disease, is associated with a reversible dilated cardiomyopathy that responds to selenium replacement. Selenium deficiency can be seen in patients receiving total parenteral nutrition and in patients from regions where food is grown in selenium-deficient soil (it was originally described in China). In the acute form, it can result in cardiogenic shock, pulmonary edema, and arrhythmias. In the chronic form, it presents as LV dilatation and systolic dysfunction. Vitamin B₁₂, folic acid, and L-lysine deficiency are not usually associated with cardiomyopathy.

4. Answer: C. Chagas disease (American trypanosomiasis) is endemic in Latin America. In infected patients, the heart muscle is invaded by the protozoan parasite Trypanosoma cruzi. Echocardiographic abnormalities include biventricular enlargement, ventricular wall thinning, mural thrombi, and a characteristic apical aneurysm.

Noncaseating cardiac granulomas are a feature of sarcoidosis. Intracavitary cardiac cystic lesions or hydatid cysts are a feature of a parasitic infection with Echinococcus granulosus. Libman-Sacks endocarditis refers to a nonbacterial endocarditis with verrucous valvular lesions that are typically found on the mitral valve in patients with autoimmune disorders and some malignancies (Tables 24-1 and 24-2).

5. Answer: C. In this patient, the E/e′ ratio is 37 consistent with marked elevation in LV filling pressures. This observation points to either anthracycline cardiotoxicity or radiation-induced myocardial disease since both of these conditions can be associated with severe diastolic dysfunction. Manifestations of radiation-induced heart disease usually occur years after therapy. Thus, the most likely explanation for these findings is early doxorubicin toxicity. In view of the severe diastolic dysfunction, a cardiac explanation for this patient’s symptoms is most likely. The mitral annular velocity should not be affected by anemia per se, although anemia in addition to diastolic dysfunction in this particular patient is a possibility. Anemia causes the mitral inflow velocity to increase secondary to a generalized high-flow state.

Doxorubicin is an anthracycline, and the incidence of cardiotoxicity is related to the cumulative dose administered. The risk is increased in patients with underlying heart disease, when anthracyclines are used concurrently with other cardiotoxic agents or radiation, and in patients undergoing subsequent hematopoietic cell transplantation. Cardiotoxicity may occur early (usually around 3 months after treatment) or may occur late (sometimes decades after treatment is completed) presenting as a nonischemic dilated cardiomyopathy.

6. Answer: B. Friedreich ataxia, an autosomal recessive degenerative disorder, is the most common hereditary ataxia and is manifested clinically by neurologic dysfunction, cardiomyopathy, and diabetes mellitus. Echocardiographic abnormalities are common, reported in 86% of patients, and are useful in confirming a diagnosis of Friedreich ataxia since cardiac involvement is not present in other ataxic disorders. The most common echocardiographic abnormality is concentric increased wall thickness occasionally mimicking hypertrophic cardiomyopathy. Asymmetric septal thickening and dilated cardiomyopathy are uncommon. Other findings include globally decreased LV function and decreased LV end-diastolic diameter. Regional wall motion abnormalities in a noncoronary distribution are typically seen in infiltrative disorders, such as granulomatosis with polyangiitis and sarcoidosis.

7. Answer: E. This patient has many of the typical cardiac manifestations of chronic renal failure. These include significant diastolic dysfunction (manifested by left atrial enlargement and restrictive filling Doppler hemodynamics), generalized valve thickening, and pericardial effusion, which is usually of no hemodynamic significance if unrelated to acute uremic pericarditis. Calcification of the valves results in both regurgitant and stenotic lesions. Mitral annular calcification is also common and is caused by derangements in calcium and phosphorous metabolism (see Tables 24-1 and 24-2). Other findings that may be seen include regional wall motion abnormalities secondary to underlying coronary artery disease. Concentric wall thickening is often seen in patients with chronic renal failure and is usually secondary to longstanding hypertension; however, another important complication of longstanding renal failure is amyloidosis. An important distinguishing feature between wall thickening secondary to hypertension versus amyloid is the low or inappropriately normal voltage seen on the ECG in amyloid. Thus, it is important to review the ECG when concentric wall thickening is appreciated in this clinical setting.

8. Answer: A. Granulomatosis with polyangiitis is a systemic necrotizing small vessel vasculitis characterized by granulomatous lesions with predilection for pulmonary and renal involvement. Recent research has identified a high frequency of echocardiographic abnormalities that appear related to granulomatosis with polyangiitis and are associated with increased mortality even though cardiac involvement is often clinically silent. Regional wall motion abnormalities that are not confined to a typical coronary artery distribution are a typical finding seen in infiltrative disorders, such as granulomatosis with polyangiitis, sarcoidosis, and cardiac amyloid. When present in younger patients with a low cardiovascular risk profile, granulomatosis with polyangiitis and sarcoid should be considered. In patients with granulomatosis with polyangiitis, the granulomatous inflammation may resolve with treatment including resolution of the regional wall motion abnormalities. Although pericardial effusions are common, they are usually small and hemodynamically insignificant. The aortic and mitral valves may be involved but valvular regurgitation is seldom severe (see Tables 24-1 and 24-2). Granulomatosis with polyangiitis may manifest as a cardiomyopathy but this is usually an isolated dilated cardiomyopathy.

9. Answer: A. Amyloid cardiac disease is caused by extracellular deposition of proteins in the myocardium. Characteristic echocardiographic features of amyloid include LV wall thickening with evidence of diastolic dysfunction. In advanced disease, wall thickening progresses resulting in a restrictive cardiomyopathy with a nondilated or small LV cavity.

Sarcoidosis is a noncaseating granulomatous disorder. Granulomatous infiltration of the myocardium can cause both systolic and diastolic dysfunction. Cardiac sarcoidosis may present as a dilated cardiomyopathy. Hemochromatosis can lead to a dilated cardiomyopathy characterized by heart failure and conduction disturbances, due to excess deposition of iron within the myocardium. Cardiac involvement in hemochromatosis can be diagnosed on the basis of clinical evaluation, specialized laboratory testing, and cardiac imaging. HIV causes dilated cardiomyopathy in approximately 1%-3% of patients with acquired immunodeficiency virus. The causes of cardiac damage include drug toxicity, secondary infection, myocardial damage by HIV, and an autoimmune process induced by HIV or other cardiotropic viruses, such as coxsackie virus, cytomegalovirus, or Epstein-Barr virus. Excessive alcohol consumption can lead to myocardial dysfunction. Alcohol is believed to be toxic to cardiac myocytes via oxygen-free radical damage and abnormal cardiac protein synthesis. Abstinence can lead to a dramatic improvement in cardiac function if the disease is diagnosed early.

10. Answer: B. Patients with sarcoid cardiac disease may have a known history of sarcoidosis, or cardiac involvement may be the first identification of the disease. The characteristic echocardiographic features seen in sarcoid heart disease include LV systolic dysfunction with regional wall motion abnormalities that do not follow a usual coronary artery distribution. Additional findings in sarcoid heart disease include atrioventricular block, abnormal wall thickness, and perfusion defects affecting the anteroseptal and apical regions.

LV dysfunction with apical dyskinesis and preserved basal cardiac function suggests stress-induced cardiomyopathy. In this disorder, typically the contractile function of the mid and apical segments of the left ventricle are depressed, and there is compensatory hyperkinesis of the basal walls, producing ballooning of the apex with systole. Stress-induced cardiomyopathy (Takotsubo syndrome) is much more common in women than in men and is frequently, but not always, triggered by an acute illness or by emotional or physical stress. Normal LV cavity size with increased LV wall thickness and LVOT obstruction suggests hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy has an autosomal dominant pattern of inheritance, characterized by hypertrophy of the left ventricle, with variable clinical manifestations and morphologic and hemodynamic abnormalities. In a subset of patients, the site and extent of cardiac hypertrophy results in obstruction to LV outflow. Less commonly, LV outflow obstruction can be seen with infiltrative cardiomyopathy such as amyloid. Right atrial and ventricular enlargement with reduced systolic function as an isolated finding would be uncommon in patients with sarcoidosis. This finding would suggest a left-to-right shunt at the atrial or pulmonary vein level. Alternatively, this could be seen in patients with arrhythmogenic RV cardiomyopathy.

11. Answer: D. The patient presents with symptoms of heart failure shortly after delivery. The clinical history is consistent with peripartum cardiomyopathy. Although the etiology of peripartum cardiomyopathy remains unclear, a number of factors have been associated with increased risk. These risk factors include age >30 years, multiparity, African descent, pregnancy with multiple fetuses, history of preeclampsia, eclampsia, postpartum hypertension, and oral tocolytic therapy.

12. Answer: B. Chest radiation can cause late cardiovascular disease, which can manifest as dyspnea. Possible causes include conduction system disease, coronary artery disease, pericardial constriction, myocardial disease, which manifests as restrictive cardiomyopathy, or endocardial disease. The endocardial disease causes valve thickening, typically affecting the aortic-mitral intervalvular fibrosa with calcification and associated valve dysfunction (see Tables 24-1 and 24-2). The right-sided valves are affected less commonly. A comprehensive echo-Doppler examination is an excellent test to determine whether there is a structural cardiac cause of dyspnea in a patient with prior radiation.

LV hypertrophy would not be expected after cardiac radiation. This finding would suggest systemic hypertension or outflow tract obstruction. Ascending aortic dilatation is not noted in patients with radiation-induced heart disease. Pericardial effusion can occur during chest radiation or early after completion but would not be expected as a late complication of chest irradiation.

13. Answer: B. A variety of cardiac abnormalities have been associated with HIV infection, including pericardial effusion, dilated cardiomyopathy, primary pulmonary hypertension, and Kaposi sarcoma of the heart. The cardiac manifestations of HIV disease have been greatly altered by the introduction of highly active antiretroviral therapy (ART). As overall survival has improved and HIV has become a chronic infection, coronary artery disease has become the most important cardiovascular complication and attention has focused on aggressive risk factor modification.

The most common clinical manifestation of HIV disease in the pre-ART era was pericardial effusion, seen in approximately 20%-40% of patients. This remains the case in the developing world and in resource-limited settings where access to ART is limited. Pericardial effusions are typically asymptomatic but serve as a marker of advanced disease and worse prognosis. It is much less common in the ART era.

Dilated cardiomyopathy has been described in 8%-16% of patients with HIV, but this data is from the pre-ART era. The prevalence is considerably lower in the ART-treated patients.

Kaposi sarcoma involving the heart is very rare and usually diagnosed as an incidental finding at autopsy. When present, it is typically found in subepicardial adipose tissue. Primary pulmonary hypertension has been reported but is a rare finding seen in less than 0.5% of AIDS patients.

14. Answer: C. Coronary vasospasm and atherosclerotic coronary artery disease are unlikely to cause the distribution of regional wall motion abnormalities seen in this patient. Apical ballooning syndrome, subarachnoid hemorrhage, and pheochromocytoma result in catecholamine-mediated severe subendocardial myocardial ischemia that can occur in the absence of epicardial coronary artery disease. The clue to the diagnosis in this patient is the prior history of labile hypertension and acute chest pain episode associated with severe headache occurring shortly after abdominal surgery. Pheochromocytoma typically presents with paroxysms of severe hypertension with associated headache, diaphoresis, and chest pain sometimes precipitated by abdominal surgery or even tumor palpation. Cardiac manifestations of pheochromocytoma include hypertensive heart disease, reversible regional wall motion abnormalities and a dilated cardiomyopathy. The diagnosis is confirmed by measuring plasma and urinary catecholamines as well as computed tomography identification of the adrenal tumor. Rarely, an extra-adrenal cardiac pheochromocytoma may present as a cardiac mass characteristically located in the atrioventricular groove. Cushing syndrome is due to excess glucocorticoid. The cardiac manifestations include moderate chronic diastolic hypertension rather than paroxysms of systolic hypertension and acute symptoms around the time of stress.

15. Answer: D. Rheumatoid arthritis may involve the heart in many ways. Coronary artery disease as well as diastolic heart failure is commonly seen in patients with rheumatoid arthritis. Antimalarial therapy used in the treatment may result in a reversible cardiomyopathy.

Despite small pericardial effusions being common, acute pericarditis and large pericardial effusions with tamponade are rare. Nevertheless, occult constrictive pericarditis may occur and if unrecognized, can result in significant morbidity and mortality. Rheumatic nodules may involve all cardiac structures including valves but infrequently result in significant valve dysfunction. Mitral valve prolapse is not generally associated with rheumatoid arthritis. Thickened and fixed tricuspid valve leaflets with tricuspid regurgitation would be expected in patients with carcinoid and drug-related valve disease (see Tables 24-1 and 24-2).

16. Answer: B. The echocardiogram demonstrates significant apical and midventricular akinesis. The patient is a postmenopausal woman with a presentation that simulates acute myocardial infarction. These features are all consistent with apical ballooning syndrome.

Transient LV apical ballooning syndrome (also known as Takotsubo cardiomyopathy or stress-induced cardiomyopathy) is a reversible cardiomyopathy triggered by profound psychological or physical stress and has a clinical presentation that is similar to acute myocardial infarction. Most patients are postmenopausal women. Proposed criteria for the diagnosis of apical ballooning require all four of the following characteristics: (1) electrocardiographic abnormalities (usually ST elevations followed by T wave inversion), (2) transient apical and midventricular wall motion abnormalities, (3) absence of obstructive coronary artery disease or acute plaque rupture, and (4) absence of other conditions, such as significant head trauma, intracranial hemorrhage, pheochromocytoma, or another etiology of myocardial dysfunction. Catecholamine-induced microvascular dysfunction is currently postulated as a likely mechanism. According to recent reports, RV apical dysfunction may be present in 30%-40% of cases. Dynamic LVOT obstruction, which is due to basal hyperkinesis, is a well-described complication of apical ballooning syndrome and may result in hypotension. Persistent LV systolic dysfunction is not an expected complication in stress-induced cardiomyopathy. Although cardiac biomarkers are always elevated, the elevation is usually mild and disproportionate to the degree of cardiac compromise. Increased urinary 5-hydroxyindole acetic acid is seen in carcinoid patients.

It is important to remember that apical ballooning syndrome is a diagnosis of exclusion and can only be diagnosed once obstructive coronary disease and acute plaque rupture have been excluded. Similar wall motion abnormalities can also result from myocardial infarction due to occlusion of a large wraparound left anterior descending artery. Hence, coronary angiography is required for the diagnosis even in the setting of typical regional wall motion abnormalities.

17. Answer: B. The two-dimensional echocardiographic findings of a pericardial effusion and an enlarged right ventricle with a D-shaped LV cavity due to pulmonary hypertension are suspicions for scleroderma. The clinical presentation of a patient who appears younger than her stated age, likely due to taut facial skin, dyspnea, arthralgias, and swelling of the hands and feet is also consistent with a diagnosis of scleroderma.

The most common primary cardiac abnormality associated with scleroderma is a pericardial effusion, often small. The myocardium may be involved by fibrosis or sclerosis and systolic and diastolic dysfunction may be present. Systemic and pulmonary hypertension are prominent secondary complications of scleroderma.

Cardiac amyloidosis is an infiltrative cardiomyopathy that results in a restrictive disease and is characterized by increased biventricular wall thickness. Hemochromatosis can lead to a dilated cardiomyopathy due to excess deposition of iron within the myocardium. Finally, cardiac manifestations of rheumatoid arthritis include pericarditis and less commonly dilated cardiomyopathy with congestive heart failure.

18. Answer: C. The TEE image demonstrates small verrucous valvular lesions on the tips of the mitral valve leaflets. In the clinical setting of a young woman with arthralgias, low-grade fever, skin rash, photosensitivity, elevated white blood cell count, pleural effusion, and no history of illicit drug use, the most likely diagnosis is SLE with Libman-Sacks endocarditis.

Libman-Sacks endocarditis (also known as nonbacterial thrombotic endocarditis, or marantic endocarditis) refers to a characteristic verrucous valvular lesion that usually affects the mitral valve in patients with SLE. The lesion is typically present on the ventricular aspect of the mitral leaflets and may extend to the chordal and papillary structures.

Ergot-alkaloid use is associated with valvulopathy and valvular regurgitation usually affecting the aortic and mitral valves. Echocardiographic features of infective endocarditis are an oscillating intracardiac mass on a valve or other cardiac structure, abscesses, and dehiscence of a prosthetic valve. The vegetations are typically on the “upstream” surface of the regurgitant jet of the affected valve, that is, on the atrial aspect of atrioventricular valves and on the ventricular aspect of the aortic valve. Rheumatic mitral valve disease is associated with thickened and calcified mitral leaflets and subvalvular apparatus, “hockeystick” deformity of the anterior leaflet and relative immobility of the posterior leaflet, and associated stenosis or regurgitation (see Tables 24-1 and 24-2).

19. Answer: C. The clue to the correct diagnosis in this case lies in the dermatologic findings. The skin lesions are angiokeratomas, which occur commonly in the groin, hip, and periumbilical areas. They are characteristically seen in patients with Fabry disease. Fabry disease is a rare X-linked inborn error of the glycosphingolipid metabolic pathway that results in accumulation of globotriaosylceramide in several organs including the skin, kidney, nervous system, cornea, and the heart leading to the clinical manifestations that usually begin in childhood or adolescence. The prominent features include severe neuropathic pain, telangiectasias and angiokeratomas, heat and exercise intolerance, and gastrointestinal symptoms, such as abdominal pain and diarrhea. Renal manifestations include proteinuria and renal failure. Cardiac involvement is usually manifested by concentric LV hypertrophy, myocardial dysfunction, aortic and mitral valve abnormalities (see Tables 24-1 and 24-2), and conduction abnormalities. In some patients, LV hypertrophy may be the only overt manifestation of the disease. Fabry disease may be present in up to 4% of patients suspected to have hypertrophic cardiomyopathy. Thus, in patients presenting with unexplained LV hypertrophy, Fabry disease should be included in the differential diagnosis. The diagnosis is usually confirmed by demonstrating decreased leukocyte or plasma alpha-Gal A activity but can also be made histologically on endomyocardial biopsy.

Acromegaly, cardiac amyloid, and Fabry disease can all result in increased LV wall thickness, and rarely asymmetric wall involvement that can mimic hypertrophic cardiomyopathy. Moreover, dynamic LVOT obstruction, typically seen in hypertrophic obstructive cardiomyopathy with systolic anterior motion of the anterior mitral leaflet may be present. In cardiac amyloid, the ECG voltage would be expected to be normal or even reduced and is thus an unlikely diagnosis in this case. This case illustrates the importance of integrating the clinical and echocardiographic findings to make an accurate diagnosis.

20. Answer: A. The skin lesion is an angiofibroma, which is a typical skin lesion seen in patients with tuberous sclerosis. Tuberous sclerosis is an inherited autosomal dominant neurocutaneous disorder that is characterized by multiorgan system involvement, including multiple benign hamartomas of the brain, eyes, heart, lung, liver, kidney, as well as skin. The diagnosis of tuberous sclerosis is made clinically. The characteristic cardiac feature of tuberous sclerosis is a rhabdomyoma, the most frequent cardiac neoplasm of childhood representing 60% of pediatric cardiac tumors. Rhabdomyomas are benign tumors that almost always present as multiple lesions. Although they are often associated with tuberous sclerosis, they can occur as an isolated finding. They typically develop in utero and are often detected on prenatal ultrasound. They occur with equal frequency in both ventricles growing in the ventricular walls or on the atrioventricular valves. They vary in size from a few millimeters to a few centimeters and may be pedunculated often obstructing ventricular inflow or outflow. The morbidity and mortality associated with these tumors reflect the potential for flow abnormalities, if they grow to sufficient size to restrict blood flow. Although many are asymptomatic, some present with heart failure, a cardiac murmur, or arrhythmia. A unique and peculiar feature of cardiac rhabdomyomas is that they usually undergo spontaneous regression in the first few years of life. There is no evidence that these tumors undergo malignant transformation and no treatment is necessary for asymptomatic tumors. Thus, the most appropriate management strategy in this patient is reassurance with follow-up echocardiography in 1 year as well as family screening for affected siblings.

21. Answer: B. This young man has Marfan syndrome. The characteristic pear-shaped dilatation of the aortic root (aortic sinuses) is characteristic and a major diagnostic criterion of this autosomal dominant inherited condition usually resulting from a fibrillin 1 gene mutation (see Table 24-1). An additional major Ghent diagnostic criterion is the history of lens dislocation. Since there is an increased risk of aortic dissection or rupture when the aortic caliber reaches a dimension of 50 mm, elective aortic root replacement is indicated as first-line therapy.

A TEE is not indicated at this time since the patient is asymptomatic and there is no suspicion of a dissection flap on the image shown. Although beta-blockers or angiotensin receptor blockers are both used in patients with Marfan syndrome to delay progression of aortic root dilatation, this patient should preferentially undergo aortic surgery in the near future due to the size of the aorta and family history of sudden death, presumed to be related to aortic dissection.

22. Answer: B. Takayasu arteritis is a chronic vasculitis of unknown etiology affecting primarily the aorta and its primary branches. Figures 24-7A and 24-7B document aortic regurgitation. Figure 24-7C demonstrates pulsed-wave Doppler of the abdominal aorta documenting diastolic flow reversals consistent with severe aortic regurgitation. The inflammation may be localized or may involve the entire vessel. The initial vascular lesions frequently occur in the middle or proximal subclavian artery. As the disease progresses, the carotids, vertebrals, brachiocephalic, right middle or proximal subclavian artery, and aorta may also be affected. The abdominal aorta and pulmonary arteries are involved in approximately 50% of patients. The inflammatory process causes thickening of the walls of the affected arteries or involved segment of the aorta. The proximal aorta may become dilated secondary to inflammatory injury. Aortic valve regurgitation may be present and is usually caused by dilatation of the proximal ascending aorta (see Table 24-1).