This chapter discusses cardiac involvement and its echocardiographic features with a number of systemic diseases including sarcoidosis, carcinoid syndrome, hypereosinophilic syndromes, thyroid disorders, hemochromatosis, muscular dystrophies, lysosomal storage diseases, connective tissue diseases, obesity, hypertension, and diabetes mellitus. Marantic endocarditis, which can occur with a number of systemic diseases, is also discussed. Still and moving images of the echocardiographic features are provided.
Keywordscarcinoid, connective tissue disease, echocardiography, hemochromatosis, hyperesosinophilia, lysosomal storage disease, sarcoid
While echocardiography is, of course, critical in the evaluation of primary diseases of the heart, it is an equally important tool in identifying and monitoring the cardiovascular sequelae of systemic diseases and their treatment. Many of these are discussed in variable detail in prior chapters including those on dilated cardiomyopathies (see Chapter 22 ), Restrictive Cardiomyopathies (see Chapter 24 ), Mitral Valve Disease (see Chapter 28 ), Diseases of the Aorta (see Chapter 34 ), and Malignant Diseases (see Chapter 42 ). This chapter focuses on those not previously covered or those conditions with manifestations that are not limited to a single cardiac structure.
Sarcoidosis is a granulomatous disease of uncertain etiology that primarily affects the lungs and lymphatic system. It has an annual incidence of 5–40 cases per 100,000 in the United States and Europe, with blacks at threefold greater risk. Cardiac involvement occurs in 25%–40% of patients overall. The hallmark of sarcoidosis is the development and accumulation of noncaseating granulomas composed of organized collections of macrophages and epithelioid cells surrounded by lymphocytes. Over time, granulomas and associated edema progress to fibrosis, thinning, and scar. Cardiac granulomas and scar occur most commonly in the basal interventricular septum and free wall of the left ventricle (particularly the basal inferior wall). Less common sites of myocardial involvement are the papillary muscles, atrial walls, and right ventricle. Involvement of the valves, pericardium, conduction system, and, rarely, the coronary arteries also occurs. Involvement tends to be patchy and, because of this, the diagnostic yield of myocardial biopsy is only 20%.
Cardiac involvement may be manifest as regional wall motion abnormalities, aneurysms (often atypically located), dilated cardiomyopathy, conduction abnormalities, arrhythmias, valvular regurgitation, pericardial effusion and rarely as acute coronary syndromes due to coronary vasculitis.
Two-dimensional transthoracic echocardiography is typically the first screening tool in the evaluation of cardiac sarcoidosis although note should be made of the important roles played by nuclear cardiology and cardiac magnetic resonance in patients with known or suspected sarcoid. Echocardiographic features of cardiac sarcoidosis include abnormal septal thickness (may be increased initially and then progress to thinning), left ventricular (LV) systolic dysfunction, and segmental wall motion abnormalities in a noncoronary distribution. Ventricular aneurysms in atypical locations, right ventricular (RV) dysfunction, valvular abnormalities, and pericardial effusion may also be seen.
The most common echocardiographic presentation of sarcoid is localized thinning of the basal interventricular septum ( Fig. 41.1 , ). This otherwise unusual pattern should raise the possibility of sarcoidosis. Ventricular aneurysms, most commonly of the basal inferior wall, may be more discrete than is typical of those caused by coronary disease ( Fig. 41.2 , ). These aneurysms may not correspond to typical coronary artery distributions and instead be due to the presence of granulomas within the myocardium. When there is segmental dysfunction, abnormal wall motion is most commonly seen in the anterior and apical LV segments. Impaired global longitudinal strain rate may also be seen in patients with cardiac sarcoidosis, often before the disease is evident clinically.
One of the earliest signs of sarcoid involvement in the heart is diastolic dysfunction, including lower mitral annular tissue velocities of the septal wall. A restrictive pattern is unusual. Valvular dysfunction is also seen in patients with sarcoid due to either granulomatous deposition within the valve leaflets or secondary to ventricular dysfunction or pulmonary hypertension. Mitral and tricuspid regurgitation are the most common abnormalities with transesophageal echocardiography (TEE) playing an important role in understanding the pathophysiology. Pulmonary hypertension and secondary RV dysfunction can result from sarcoid lung involvement and be detected on echocardiographic evaluation. Direct involvement of the right ventricle by granuloma deposition can lead to regional or global RV systolic dysfunction.
Echocardiographic abnormalities may occur in the absence of extracardiac evidence of disease, symptoms, or ECG abnormalities. Conversely, the absence of echocardiographic findings does not exclude the diagnosis of cardiac sarcoid (negative predictive value of only 32%). Fig. 41.3 provides a composite reference for the cardiac findings with cardiac sarcoid.
Hypereosinophilic Syndrome (Loeffler Endocarditis)
Hypereosinophilic syndrome (HES) refers to a family of disorders that share blood eosinophil counts of >1.5 × 10 9 /L and have directly attributable organ damage, frequently the heart. The hypereosinophilia may be idiopathic or due to leukemia, chronic parasitic infections, allergies, granulomatous disease, hypersensitivity, or neoplastic disorders. There is overlap with Churg-Strauss syndrome and endomyocardial fibrosis.
There are three phases of the cardiac involvement of HES: an acute inflammatory and necrotic state, followed by thrombotic and then fibrotic stages. Either or both ventricles of the heart may be affected and show endocardial thickening of the inflow regions and ventricular apices ( Fig. 41.4 , ). There is also regional thickening of the basal inferior segment of the left ventricle that may impair the movement of the posterior leaflet of the mitral valve and cause significant mitral regurgitation, a mechanism that can be delineated by TEE. The apex may be filled with thrombus contributing to the appearance of Merlon sign, hypercontractility of the base with dysfunction of the apex. Contrast perfusion imaging may be helpful in separating thrombus from muscle in instances where there might be confusion between HES and apical hypertrophic cardiomyopathy. The atria are generally dilated, and there may be additional features of diastolic dysfunction and restrictive myopathy in later stages as well as pericardial effusion.
The main mechanism by which thyroid disease affects the cardiovascular system is perturbation of the amount of thyroid hormone present in the circulation. Both hypothyroidism and hyperthyroidism have long been known to produce changes in the cardiovascular system by causing changes in cardiac contractility, myocardial oxygen consumption, and cardiac output. In addition, both hyperthyroidism and hypothyroidism are known to affect the electrical system of the heart and predispose afflicted individuals to atrial fibrillation and ventricular arrhythmias. Because hyperthyroidism is known to be associated with pulmonary hypertension, LV dysfunction, and mitral valve prolapse, echocardiographic evaluation of the heart in patients with hyperthyroidism should address right heart function and estimation of pulmonary artery systolic pressure, LV systolic function, and mitral valve structure and function. More sophisticated tools such as strain and Doppler tissue imaging are important to assess diastolic function and identify subclinical systolic dysfunction.
Hypothyroidism is associated with decreased cardiac contractility and cardiac output, altered diastolic function, and heart failure. Echocardiographic evaluation of the patient with hypothyroidism should focus on LV systolic and diastolic function, again taking advantage of strain and Doppler tissue imaging indices. Pericardial effusion may also be present and may cause tamponade. Lipid levels are typically elevated in patients with hypothyroidism, and these patients may also exhibit accelerated atherosclerosis. Therefore, stress echocardiography in this subset of patients may be helpful in evaluating pain syndromes.
Carcinoid Heart Disease (see also Chapter 30 )
Carcinoid tumors are neuroendocrine malignancies most commonly located in the gastrointestinal tract. The most frequent locations are the appendix and terminal ileum. Rarely, they may be found in the bronchus and gonads. The presentation of the majority of patients is related to detection of the primary tumor alone, but carcinoid heart disease may be the presenting problem in 20% of patients, making this a diagnosis that can be made in the echo lab. Frequently, carcinoid heart disease is accompanied by other elements of carcinoid syndrome (secretory diarrhea, flushing, and bronchospasm).
The hallmark of carcinoid heart disease is valvular thickening and leaflet retraction due to the paraneoplastic effects of vasoactive substances secreted by the tumors. These substances include serotonin (5-hydroxytryptamine), 5-hydroxytryptophan, histamine, tachykinins, bradykinins, and prostaglandins. Pathologic changes include endocardial plaques of fibrous tissue that typically involve the tricuspid and pulmonary valves, right sided cardiac chambers, vena cavae, pulmonary artery, and coronary sinus. The tissue is most commonly deposited on the ventricular aspect of the tricuspid valve and pulmonary arterial aspect of the pulmonic valve, and the underlying architecture is not altered. Generally, only carcinoid tumors that have metastasized to the liver affect the heart and involvement is typically limited to the right side, because the vasoactive substances are largely inactivated in the lungs. The presence of left-sided involvement, which occurs in 10% of cases, implies the presence of an intracardiac right- to-left shunt or pulmonary metastases.
On echocardiography, the most common finding is tricuspid valve leaflet and subvalvular apparatus thickening, shortening, and retraction so that the leaflets acquire a drumstick appearance. The valve leaflets cannot coapt normally with resultant tricuspid regurgitation, which is often severe ( Fig. 41.5 , ). The continuous-wave Doppler profile may show a characteristic “dagger” shape, corresponding to an early peak and rapidly declining RV to right atrium (RA) pressure gradient, corresponding to rapid equalization of the RV and right atrial pressures. Because such flow will be color-coded as monochromatic, rather than the typical mosaic appearance of valve regurgitation, the severity may be underestimated by color Doppler. However, tricuspid stenosis is rare. The pulmonic valve may also be affected and appear thickened and retracted, resulting in either pulmonic regurgitation or stenosis. In addition to cusp involvement, the annulus may be constricted, but calcification of the valve is generally not seen in carcinoid heart disease.