Many systemic diseases may have manifestations in the heart. This section describes those that are most likely to be included on the examination.
Hyperthyroidism Effects
The cardiovascular manifestations of hyperthyroidism include an
increase in heart rate, stroke volume, and cardiac output. Peripheral vascular resistance is decreased, and thus there is a widened pulse pressure. All of these lead to an increase in myocardial oxygen con-sumption and therefore may precipitate angina. Other potential symptoms include palpitations, tachycardia, presyncope or syncope, and shortness of breath on exertion.
• The effects of hyperthyroidism lead to increased myocardial work and oxygen consumption and therefore may precipitate angina and arrhythmias.
Symptoms
Typical clinical scenario: An elderly woman (hyperthyroidism is 4-8 times as common in women as in men) presents with weight loss, weakness, and tachycardia and may or may not have angina or atrial fibrillation (15%). Examination shows tremor of fingers and tongue;
goiter may or may not be present.
Physical Examination
Common physical findings are tachycardia and a bounding pulse with a wide pulse present with forceful apical pulse and a systolic ejection murmur due to increased flows. Cardiac arrhythmias are common, particularly supraventricular tachycardia and atrial fibril-lation. Atrial fibrillation occurs in 10% to 20% of patients with hyperthyroidism. Therefore, thyrotoxicosis should always be sus-pected in patients with atrial fibrillation and the thyroid function should be checked.
• Findings of hyperthyroidism: tachycardia, bounding pulse, force-ful apical impulse, widened pulse pressure, and systolic ejection murmur.
• Cardiac arrhythmias are common, especially atrial fibrillation.
• Thyrotoxicosis in patients with atrial fibrillation.
Treatment
Treatment of underlying hyperthyroidism usually leads to reversal of cardiac symptoms. If atrial fibrillation is present, the risk of emboliza-tion is high and anticoagulaemboliza-tion should be instituted. Cardioversion should not be attempted until a euthyroid state is achieved.
Hypothyroidism Effects
Hypothyroidism leads to cardiac enlargement and decreased func-tion due to infiltrafunc-tion of the myocardium with mucoproteins. This disorder decreases the metabolic rate and circulatory demand and causes bradycardia, decreased myocardial contractility and stroke volume, and an increase in peripheral resistance. In one-third of patients, a pericardial effusion is present. The cardiomyopathy of hypothyroidism is reversible if detected early. The hypothyroid state can increase cholesterol levels and accelerate atherosclerosis.
Symptoms
Typical clinical scenario: An elderly patient presents with depression, lethargy, and slowed mentation. Examination shows hair loss on the Chapter 3 Cardiology 55
scalp and eyebrows and macroglossia. Sinus bradycardia usually is present. Chest radiography shows increased cardiac size.
Electrocardiography shows low voltage of QRS with prolonged intervals of QRS, PR, and QT.
• Hypothyroidism may lead to dilated cardiomyopathy.
Physical Examination
There may be cardiac enlargement due to the myocardial disease or to a commonly found pericardial effusion. The volume of pulses is decreased because of a decrease in myocardial contractility.
• Physical findings in hypothyroidism: cardiac enlargement, reduced myocardial contractility, and pericardial effusion (this occurs in a third of patients).
• Heart failure is less common, but it is reversible if found early.
• Atherosclerosis is accelerated.
Treatment
Treating the underlying cause likely leads to reversal of cardiac involvement.
Diabetes Mellitus Effects
This condition frequently is associated with premature development of atherosclerosis. It is two times more prevalent in diabetic men and three times more prevalent in diabetic women than in a nondiabetic population. Patients with diabetes have an increased prevalence of hypertension and hyperlipidemia. Angina and myocardial infarction may often manifest as either atypical symptoms or silent ischemia.
In fact, congestive heart failure may be the first manifestation of coronary artery disease among the diabetic population. There is also some evidence that cardiomyopathy unassociated with epicardial coronary atherosclerosis exists. This is speculated to be caused by small-vessel disease.
Treatment
The BARI (Bypass and Angioplasty Revascularization Investigation) trial found that coronary artery bypass grafting reduced the death rate more than percutaneous transluminal coronary angioplasty in patients with diabetes mellitus and multivessel coronary artery disease. However, stents and glycoprotein IIb/IIIa inhibitors were not routinely used in that trial. Patients with diabetes seem to have a higher complication rate than nondiabetics regardless of the inter-ventional strategy chosen. If percutaneous intervention is chosen, glycoprotein IIb/IIIa inhibition and stent placement have better long-term control.
Preventive strategy is important. Trials have shown that aggressive management of traditional risk factors for coronary artery disease lowers mortality. Diabetic-specific risk factors for coronary artery disease include glycemic control and urinary protein excretion.
Randomized control trials have found that the use of antihy-pertensives for aggressive lowering of blood pressure (systolic pressure
≤120 mm Hg, diastolic pressure ≤80 mm Hg) reduces mortality.
Statins and fibrates are effective for primary and secondary prevention of coronary artery disease in patients with both diabetes and hyper-lipidemia. Aspirin also is effective for primary and secondary prevention.
Angiotensin-converting enzyme inhibitors as a class reduce cardiovas-cular events and mortality in patients with diabetes who are older than 55 years and have additional risk factors (HOPE trial).
• Fatal myocardial infarction is more common in diabetics than in nondiabetics.
• Lipid lowering and glycemic control are important in the pre-vention of coronary artery disease.
• The prevalence of hypertension is increased in diabetes, but aggres-sive control lowers mortality.
• The incidence of silent myocardial ischemia is high.
• Angiotensin inhibition should be considered for primary and secondary prevention in diabetics with known vascular disease or with one or more traditional risk factors.
• Aspirin is beneficial for primary and secondary prevention in diabetes.
Amyloidosis Effects
Amyloidosis is the result of multiple diseases leading to the extra-cellular deposition of insoluble proteins in organs. Organs involved typically are the liver, kidney, heart, gastrointestinal tract, and nervous tissue. In primary amyloidosis, nearly 90% of patients have clinical manifestations of cardiac dysfunction. The heart is enlarged, most often a result of thickened ventricular myocardium from the pro-tein infiltration. Abnormalities of diastolic function, conduction, and ultimately systolic dysfunction can occur. Amyloid deposition in the cardiac valves leads to atrioventricular valvular regurgitation, which is usually not severe. Secondary amyloidosis occurs in association with chronic disease such as rheumatoid arthritis, tuber-culosis, chronic infection, neoplasia (especially multiple myeloma), and chronic renal failure. Cardiac involvement occurs in secondary amyloidosis, but it is usually not a prominent feature. The entity of senile amyloidosis does exist, and the heart is the organ most com-monly involved. The prevalence of this disorder increases after age 60 years. Familial amyloidosis is autosomal dominant. The characteristic amyloid protein is pre-albumin, and it can involve the heart.
Clinical Features
The following can occur in cardiac amyloid involvement: conges-tive heart failure, arrhythmias, sudden death, angina, chest pain, pericardial effusion (usually not hemodynamically significant), and murmurs. The natural history of the disease is usually intractable because of ventricular cardiac failure. Diastolic abnor-malities are early common manifestations and are classic for “restric-tive cardiomyopathy.” The restric“restric-tive classification indicates a poor prognosis.
Symptoms
Typical clinical scenario: The diagnosis of amyloidosis should
be given particular consideration when a patient (usually 40-70 years) presents with dyspnea and progressive edema of the lower extremity. Ancillary conditions such as vocal hoarseness, carpal tunnel syndrome, or peripheral neuropathy may be present and point to the systemic nature of the disease. The patient often has received treatment with digoxin and a diuretic but has had little improvement. The key finding is a low-voltage QRS complex with or without other conduction abnormalities (such as increased PR interval or bundle branch block) coupled with echocardio-graphic findings of thick walls and usually preserved ventricular function.
Diagnosis
The diagnosis of cardiac involvement is made on the basis of elec-trocardiography, which shows a classic low-voltage QRS complex, which is nonspecific. In addition, echocardiography is particularly useful. Classically, echocardiography shows an increase in left ven-tricular wall thickness, in contradistinction to the small (or normal) voltage on electrocardiography (Fig. 3-12). Tissue characteristics on echocardiography are often described as granular. The atria gen-erally are dilated. The cardiac valves may show some thickening and regurgitation. There may be a small pericardial effusion.
Diastolic function generally is abnormal; in the early stages of the disease it shows a prolongation of the relaxation, and in the later stages it shows restrictive filling (consistent with high left ventric-ular filling pressures).
• In primary amyloidosis, 90% of patients have cardiac dysfunction.
• Echocardiographic features: thickened ventricular walls, granular myocardial appearance, dilated atria.
• Abnormal diastolic function: consistent with delay and relaxation in the early stages and with restrictive (increased ventricular filling pressure) patterns in the later stages.
• Hallmark: normal to reduced voltage on electrocardiography, in the face of “thick” walls on echocardiography.
Treatment
Treatment of the underlying cause may lead to a better prognosis.
However, once cardiac amyloidosis is diagnosed, the prognosis generally is poor. Referral to a tertiary center with expertise in amyloid-osis is warranted because experimental protocols have evolved into worthy treatments, such as stem cell transplantation in primary amy-loidosis.
Hemochromatosis Effects
Hemochromatosis is an iron-storage disease. There is a primary or a secondary form related to exogenous iron (usually from repeated blood transfusions) deposits within the cardiac cells. Cardiac hemochromatosis generally does not occur alone and is accompanied by involvement of other organ systems, primarily the tetrad of diabetes, liver disease, brown skin pigmentation, and congestive heart failure.
Chapter 3 Cardiology 57
I
II
III
II
V1
V5
aVR
aVL
aVF
V1
V2
V3
V4
V5
V6
Fig. 3-12.Low-voltage complexes on electrocardiography in a patient with cardiac amyloidosis.
The condition may present with cardiomegaly, congestive heart failure, and arrhythmias. This disease has features of poor systolic and diastolic function. Once clinical cardiac symptoms appear, the prognosis is very poor unless treatment is initiated with a combination of phlebotomy and iron chelation.
Symptoms
Typical clinical scenario: Patients are middle-aged and present with symptoms and signs of heart failure. Clues to hemochromatosis are a well-tanned patient with diabetes or, at minimum, increased blood glucose value, arthralgias, and loss of libido. The diagnosis is made on the basis of increased transferrin saturation and increased serum ferritin value.
• Hemochromatosis is related to iron deposits within cardiac cells.
• Cardiac involvement in hemochromatosis does not occur alone;
other organs are involved.
• The key to diagnosis is the tetrad of diabetes, liver disease, skin hyperpigmentation, and congestive heart failure.
Carcinoid Heart Disease Effects
Carcinoid tumor is a malignant tumor. The primary site, usually gastrointestinal (terminal ileum), can produce a classic syndrome (in about 4% of patients) when metastatic to the liver or lungs. Malignant carcinoid tumors produce serotonin-like substances that cause cuta-neous flushing, wheezing, and diarrhea, which is the carcinoid syn-drome. These circulating substances are also toxic to valvular tissues.
They are metabolized in the liver and lungs. Cardiac involvement occurs in approximately 50% of patients after hepatic or pulmonary metastasis. Therefore, toxic effects generally affect right-sided car-diac valves unless there is a shunt (generally a patent foramen ovale) that allows right-to-left movement of blood substances. Carcinoid lesions are fibrous plaques that form on valvular endocardium. The valve leaflets become thickened, relatively immobile, and retracted.
The result is regurgitation with an element of stenosis of both the tricuspid and the pulmonary valves.
Symptoms
Typical clinical scenario: A 50- to 70-year-old patient presents with weight loss, fatigue, watery diarrhea (>10 stools daily), dyspnea on exertion, and audible wheezes. The patient has a red complexion and notes feeling hot flashes intermittently.
Physical Examination
Examination typically reveals a prominent v wave in an increased jugular venous pressure profile, a pulsatile liver that may be enlarged, ascites, and usually considerable peripheral edema.
Diagnosis
Electrocardiography typically shows right ventricular hypertrophy and right bundle branch block. Diagnosis is made by identification of a thickened tricuspid valve and pulmonary valve (left-sided valves only if a shunt is present) and the finding of liver metastasis on
com-puted tomography, confirmed by a 24-hour urine study for 5-hydroxyindoleacetic acid. Acquired tricuspid and pulmonary steno-sis with or without regurgitation is rare and should always raise the possibility of carcinoid heart disease.
• Carcinoid tumors produce serotonin-like substances that cause flushing, wheezing, and diarrhea.
• Changes occur in the tricuspid and pulmonary valves. Dominant lesions are tricuspid regurgitation, pulmonary regurgitation, and stenosis.
• Acquired tricuspid and pulmonary stenosis with or without regur-gitation is rare and should always raise the possibility of carcinoid heart disease.
Treatment
Treatment of underlying carcinoid tumor is important for relief of symptoms. If there is evidence of right heart failure (intractable edema, ascites, dyspnea), then intervention may be warranted. Surgical therapies include tricuspid valve replacement and pulmonary valve resection.
Hypereosinophilic Syndrome Effects
This syndrome affects young patients, generally male, who have a persistent eosinophil concentration of more than 1.5 × 109/L. The causes are several, including idiopathic hypereosinophilia, Löffler endocarditis, reactive or allergic eosinophilia, leukemic or neoplastic eosinophilia, or Churg-Strauss syndrome. All of these may have cardiac manifestations.
Clinical Features
Patients present with weight loss, fatigue, dyspnea, syncope, and systemic embolization. Cardiac manifestations include arrhythmias, myocarditis, conduction abnormalities, and thrombosis. Eosinophilic deposition occurs in the heart, where a clot forms in the apices of the ventricles and in the inflow portions under the mitral and tricuspid valves. This ultimately leads to matting down of the atrioventricular valve and causes considerable regurgitation. The clot ultimately scars, leading to endomyocardial fibrosis and restrictive cardiomyopathy.
• Hypereosinophilic syndrome may be present in patients with a persistent eosinophil value >1.5 × 109/L.
• Hypereosinophilic syndrome presents with restrictive car-diomyopathy, atrioventricular valve regurgitation, and systemic embolization.
• Unexpected thromboembolism in the presence of normal left ventricular function should raise suspicion of this syndrome.
• Churg-Strauss syndrome should be considered if pulmonary involvement is present.
• Typical clinical scenario: A young patient has fatigue, weight loss, and dyspnea of relatively recent onset (months) and presents to the emergency department because of new right-sided weakness.
Echocardiography shows a normal to small left ventricle, mitral valve abnormalities, and apical ventricular thrombus. The
diag-nosis is confirmed on the basis of a complete blood count with differential count.
Systemic Lupus Erythematosus
Systemic lupus erythematosus may involve any of the cardiac struc-tures. Special features of involvement include the antiphospholipid syndrome, Libman-Sacks endocarditis, and congenital heart block in the offspring of mothers with lupus.
Offspring of mothers with anti-La and anti-Ro antibodies are at risk for development of neonatal lupus, characterized by myocardi-tis and inflammation and fibrosis of the conduction system, which may lead to congenital heart block.
Cardiac involvement in patients with systemic lupus erythe-matosus may include pericarditis, which is characterized by a positive antinuclear antibody in the pericardial fluid, myocarditis (more com-mon in patients with anti-Ro antibody), a valvulopathy, coronary arteritis, and Libman-Sacks endocarditis.
Libman-Sacks endocarditis is a noninfective vegetation that may be present in up to 50% of patients with systemic lupus ery-thematosus. It does not generally embolize or interfere with valvular function.
• The offspring of mothers with anti-La and anti-Ro antibodies are at risk for congenital heart block.
• Approximately a third of patients with systemic lupus erythe-matosus may have clinical evidence of cardiac involvement, includ-ing pericarditis, endocarditis, myocarditis, and coronary arteritis.
• Typical clinical scenario: A mother with a history of multiple spontaneous abortions carries a baby to term, and the baby is born with complete heart block.
Scleroderma
Scleroderma affects the skin with sclerotic changes, the esophagus with dysphagia, and small vessels with manifestations such as Raynaud phenomenon. Cardiac involvement is manifested by intramural coronary involvement and immune-mediated endothelial injury, which is often associated with the Raynaud phenomenon clinically.
Cardiac involvement is the third most common cause of mortality in patients with scleroderma. Conduction defects occur in up to 20% of patients, and a pericardial effusion is found in a third of patients, but it is often asymptomatic. Indirect cardiac involvement due to pulmonary hypertension and cor pulmonale is frequent.
• Cardiac involvement is the third most common cause of mortal-ity in patients with scleroderma.
• Coronary vasculitis is associated with clinical Raynaud phe-nomenon.
• Conduction defects may occur in up to 20% of patients.
Rheumatoid Arthritis
Rheumatoid arthritis may be associated with involvement of nearly all cardiac components, including pericardium, myocardium, valves, coronary arteries, and aorta. Rheumatoid arthritis may cause both granulomatous and nongranulomatous inflammation of valve leaflets, which rarely leads to severe valvular incompetence. Pericarditis of
rheumatoid arthritis usually is associated with a low glucose level and complement depletion in the pericardial fluid. Rheumatoid nod-ules may be deposited in the conduction system, leading to degrees of heart block. Aortitis and pulmonary hypertension due to pul-monary vasculitis are very rare complications of rheumatoid arthritis.
• Pericardial fluid accumulation in patients with rheumatoid peri-carditis will be low in glucose and complement and is associated with nodular rheumatoid arthritis.
• Granulomatous involvement in the conduction system may lead to heart block.
• Nongranulomatous and granulomatous involvement of valvular tissue may lead to incompetence of cardiac valve structures.
Ankylosing Spondylitis
Aortic dilatation and aortic regurgitation may be present in approx-imately 10% of patients. Aortic valve cusps become distorted and retracted, leading to considerable aortic regurgitation. The conduc-tion system may become involved as a result of both fibrosis and inflammation.
Marfan Syndrome
Marfan syndrome is an autosomal dominant condition associated with degenerative elastic tissues, leading to arachnodactyly, tall stature, pectus excavatum, kyphoscoliosis, and lenticular dislocation.
Common cardiac manifestations include mitral valve prolapse, aortic regurgitation due to aortic dilatation, and increased risk of aortic dissection. Long-term β-adrenergic blockade has been shown to decrease the rate of aortic dilatation and potential for dissection.
Dissection occurs rarely in an aorta less than 55 mm in diameter.
When dissection occurs, it tends to start in the ascending aorta and extend along the entire aorta.
Friedreich Ataxia
This is an autosomal recessive neurologic disorder that involves the heart in up to 90% of cases. It usually manifests as a symmetric hypertrophy and less commonly as a dilated cardiomyopathy.
Osteogenesis Imperfecta
Brittle bones, blue sclera, and deafness are the hallmarks of this con-dition, which leads to a lack of collagen-supporting matrix. Ultimately, there is a degeneration of elastic tissues, including aortic root dilata-tion, aortic regurgitadilata-tion, annular dilatadilata-tion, and chordal stretch leading to significant atrioventricular regurgitation.
Lyme Disease
Lyme disease is a spirochete infection by Borrelia burgdorferi organ-isms. Up to 10% of cases have clinical cardiac involvement. Cardiac manifestations include atrioventricular block and Lyme carditis.
The diagnosis is generally made by biopsy of the right ventricular myocardium or gallium scanning.
Acquired Immunodeficiency Syndrome (AIDS)
Clinically apparent cardiac involvement may occur in up to 10% of patients with AIDS. Cardiac involvement has been reported as a Chapter 3 Cardiology 59
myocarditis in up to 50% of patients at autopsy. This may be asso-ciated with ventricular arrhythmias, dilated cardiomyopathy, peri-carditis, or infectious or malignant invasion of the cardiac structures.
Cardiac Trauma
Contusion, in the acute stage, may lead to arrhythmia, increased
Contusion, in the acute stage, may lead to arrhythmia, increased