Myxoma

Often a diagnostic challenge, myxoma, a benign, solitary neoplasm slowly proliferating, microscopically resembles an organized clot, which often obscures its identity as a primary cardiac tumor. The pedunculated mass is believed to arise from undifferentiated cells in the fossa ovalis and adjoining endocardium projecting into the left atrium (LA) and right atrium (RA) 75% and 20% of the time, respectively. However, myxomas appear in other locations of the heart, even occupying more than one chamber.¹⁴ The undifferentiated cells of a myxoma develop along a variety of cell lines, accounting for the multiple presentations and pathologies observed.¹⁵ Besides a variable amount of stroma, myxomas include hemorrhage, hemosiderin, thrombus, and calcium (Figure 22-1). Myxomas predominate in the 30- to 60-year-old age range, but any age group may be affected. More than 75% of the affected patients are women.¹⁶ Although most cases occur sporadically, 7% to 10% of atrial myxomas will occur in a familial pattern with an autosomal dominant transmission pattern.¹⁷

Figure 22-1 A, Parasternal long-axis view of large, firm left atrial myxoma remaining impacted in left atrium. Tumor (T) contains a central region of echolucency (arrowheads) that corresponds to an area of liquefaction. B, Cut section of gross specimen of myxoma. LV, left ventricle; RV, right ventricle; VS, ventricular septum.

(From Fyke FE III, Seward JB, Edwards WD, et al: Primary cardiac tumors: Experience with 30 consecutive patients since the introduction of two-dimensional echocardiography. J Am Coll Cardiol 5:1465, 1985, by permission of the American College of Cardiology.)

Rarely discovered by incidental echo examination, myxomas may manifest a variety of symptoms. The classic triad includes embolism, intracardiac obstruction, and constitutional symptoms. Approximately 80%¹⁴ of individuals will present with one component of the triad. Up to 10% may be asymptomatic even with mitral myxomas that arise from both atrial and ventricular sides of the anterior mitral leaflet.¹⁸ The most common initial symptom, dyspnea on exertion,¹⁶ reflects mitral valve obstruction usually present with left atrial myxomas (Figure 22-2). Because of the pedunculated nature of some myxomas, temporary obstruction of blood flow may cause hemolysis, hypotension, syncope, or sudden death. Other symptoms of mitral obstruction similar to mitral stenosis such as hemoptysis, systemic embolization, fever, and weight loss also may occur. If the tumor is obstructing the mitral valve, a “tumor plop” may be heard after the second heart sound on chest auscultation. The persistence of sinus rhythm in the presence of such symptoms may help distinguish atrial myxoma from mitral stenosis. Severe pulmonary artery hypertension (PAH) without significant mitral valve involvement suggests recurrent pulmonary emboli known to occur with a myxoma in the RA or right ventricle (RV). Occasionally, right-sided tumors may appear as cyanotic congenital heart lesions because of intracardiac shunting.¹⁹

Figure 22-2 A large myxoma (arrow) is seen in the left atrium with its point of attachment at the interatrial septum. Note the irregular shape and nonhomogenous echogenicity of the tumor.

Recurrent fragmentation and embolization of the gelatinous-like tumor usually appear with systemic manifestations and are characteristic of myxoma. It is the smaller myxoma in the LA that does not create hemodynamic complications, exists for years undiagnosed, and is more likely to cause embolization.⁷ Cerebral aneurysms often exist in patients with recurrent systemic embolization from intracardiac myxoma probably secondary to damage by the systemic tumor emboli. The kidneys also are more susceptible to damage from myxoma emboli. Constitutional symptoms such as malaise, fever, and weight loss occur in about one third of patients, reflecting a possible autoimmune component but also delaying the diagnosis. Differential diagnosis includes endocarditis, connective tissue disorders, and malignancies. In general, the anatomic type of myxoma portends the clinical presentation. The solid, ovoid tumors are more often associated with CHF, whereas papillary myxomas present with cerebral embolization.²⁰ Tumor size does not correlate with symptoms.¹⁶

Findings on a chest roentgenogram of a myxoma may be absent in one third of patients. Calcification on the chest roentgenogram is more diagnostic of right atrial myxoma, but rarely presents in left atrial myxoma. Before the availability of echo, angiography was used to identify all myxomas, but currently is probably only useful to determine coronary anatomy if considered necessary.² Computerized tomography (CT) and MRI can help delineate the extent of the tumor and its relations to surrounding cardiac and thoracic structures.²¹ MRI is especially valuable in the diagnosis of myxoma when masses are equivocal or suboptimal by echo, or if the tumor is atypical in presentation.¹⁴ Difficulty may arise in differentiating thrombus from myxoma because both are so heterogenous.

Transthoracic echocardiography (TTE) is excellent for identifying intracavitary tumors because it is noninvasive, identifies tumor type, and permits complete visualization of each cardiac chamber (see Figure 22-1).²² It is the predominant imaging modality for screening.² Transesophageal echocardiography (TEE) increases the diagnostic potential, as the nature of the tumor according to location, dimensions, number of masses, and echogenic pattern is better identified.²³ Specifically, it yields morphologic detail in the evaluation of cardiac tumors, including points of tumor attachment and degree of mobility.

Myxomas have a typical echo appearance and often are irregular in shape with protruding fronds of tissue. There may be areas of calcification, and the echogenicity of the mass may not be homogenous.²⁴ The presence of a large mass in the LA with an attachment to the interatrial septum is highly suggestive of myxoma. However, it must be emphasized that echo cannot provide a tissue diagnosis. Rarely, thrombus can be attached to the atrial septum.²⁵ The degree of obstruction to ventricular filling caused by the tumor may be evaluated with Doppler echo (Figure 22-3). Qualitatively, color-Doppler imaging will show aliasing and flow acceleration through the atrioventricular valve when obstruction is present. Continuous-wave Doppler imaging is able to quantify the gradient between the atrium and ventricle. Before surgery, the goal of echo is to determine the site of tumor attachment, the absence of multiple masses, and to ensure that the tumor is not attached to the valve leaflets. If this cannot be accomplished with TTE, a TEE examination should be performed to aid in planning the surgical approach.

Figure 22-3 Left, A large left atrial myxoma (arrow) can be seen prolapsing through the mitral valve into the left ventricle during diastole. Middle, Color-Doppler imaging shows aliasing of flow indicating obstruction of left ventricular filling during diastole. Indeed, when a continuous-wave Doppler signal is placed through the mitral annulus, a gradient of 8 mm Hg is seen between the left atrium and ventricle. The obstruction to ventricular filling caused by the myxoma prolapse would be equivalent to moderate mitral valve stenosis. LA, left atrium; LV, left ventricle.

Currently, evaluation of cardiac tumors is a Class II indication for intraoperative TEE (supported by weaker evidence and expert opinion).²⁶ When the primary reason for cardiac surgery is removal of an intracardiac mass, an intraoperative TEE evaluation should take place before the surgical incision to ensure that the mass is still present and has not embolized out of the heart (or dissolved as in the case of intracardiac thrombus). In the case of myxoma, an intraoperative examination in the presence of the surgeon can aid in finalizing the surgical plan. After tumor removal, the goal of TEE is to ensure that all visible mass was removed and there was no damage to adjacent structures. Specifically, in the case of a myxoma attached to the atrial septum, it is important to ensure that there is no interatrial shunting after removal. If the tumor was attached to, or near, a valve apparatus, the examiner must determine that the valve is competent after tumor removal.

The first surgical resection of an atrial myxoma was performed in 1954. Subsequently, surgical resection has been recommended even if the myxoma is discovered incidentally, mainly because the risk for embolization to the central nervous system may be 30% to 40%. Generally, the time interval between onset of symptoms and surgical resection is about 4 months, but surgery has been delayed for 10 years.¹⁶ Surgery is associated with a mortality rate of 0% to 7%.^1,7 More importantly, it recently was documented for the first time that the long-term survival of an individual who underwent resection of myxoma was no different from an age- and sex-matched population.¹²

Other Benign Tumors

Papillomas (papillary fibroelastoma) are rare tumors but are the third most common primary cardiac tumor (after myxoma and fibroma).⁵ Initially thought to be incidental findings during autopsies, today most are discovered in living patients.²⁸ Mostly singular (90%), 1 to 4 cm in size, highly papillary, pedunculated, and avascular, papillomas are covered by a single layer of endothelium containing fine elastic fibrils in a hyaline stroma. Macroscopically, they resemble sea anemones. They originate most commonly from valvular endocardium,²⁹ usually involving the ventricular surface of the aortic valve or the atrial surface of the mitral valve, but infrequently rendering the involved valve incompetent. They account for 75% of all primary cardiac valvular tumors.^12,30 Adults between the ages of 40 and 80 primarily are affected, with the mean age at the time of detection of 60 years.⁵ Many patients are asymptomatic, so it is not surprising that 47% of these tumors are discovered incidentally during echo, catheterization, or even cardiac surgery. Echocardiographically, fibroelastomas have a typical appearance (Figure 22-4). They usually are small (mean size, 12 × 9 mm) and their motion is independent from that of the attached valve leaflet.³¹ They may appear similar to vegetations seen in endocarditis, or they may be confused with Lambl’s excrescences, which tend to be more nodular in appearance.

Figure 22-4 The typical appearance of a fibroelastoma (arrow) attached to what is likely the right coronary cusp of the aortic valve. This tumor is thin, and its motion is independent from that of the aortic leaflet.

Currently, many tumors are found in a search to find the cause of embolic symptoms. These symptoms are most common when the aortic valve is involved. Previously believed to be harmless, postmortem studies have shown a high incidence of embolization to the cerebral and coronary circulations.⁴ Not surprisingly, symptoms often are related to stroke or transient ischemic attack and myocardial infarction (MI). Although embolization may be a tumor, it may be a thrombus because tumors are excellent sites for thrombus formation.⁵ It is important that the diagnosis is made because acute valvular dysfunction and even sudden death may occur.²⁹ Surgical resection is curative but may require valvular repair or replacement in one third of cases.²⁸ Recurrence is rare.

The incidence of cardiac lipomas⁴ is similar to papillary fibroelastoma. They occur as intracavitary tumors, intramyocardial masses, and pericardial tumors. Histologically, they usually consist of encapsulated groups of mature fat cells. Patients with these tumors often are asymptomatic, but if they occur in an intracavitary location, they may resemble myxomas. An intramyocardial location may provoke arrhythmias and conduction abnormalities. Pericardial lipomas are associated with tamponade and cardiac compression. These tumors tend to enlarge over time, and when symptoms appear, surgical excision is required.

Rhabdomyomas are primarily childhood tumors (majority before 1 year of age) located intramyocardially, and arise from all areas of the heart and at multiple locations of the heart. Tuberous sclerosis often is associated with these tumors.³² They represent 45% of all benign tumors of childhood, but only 1% of benign adult primary cardiac tumors.⁴ As pedunculated masses, rhabdomyomas usually originate in the ventricle, leading to inflow and outflow ventricular obstruction, and on the atrioventricular valves.⁵ Symptoms are caused by the obstruction of blood flow and arrhythmias, but life-threatening complications are rare. Although surgical resection may be necessary in 25% of cases, these tumors most often resolve spontaneously. Because of their space-occupying properties, rhabdomyomas may mimic other congenital defects such as left hypoplastic heart syndrome.

Fibromas are connective tissue tumors found primarily in children, making up 15% of pediatric benign primary cardiac tumors.⁴ They are usually solitary, located in the wall of the heart, and often involve the apical or septal areas of the left ventricle (LV) (Figure 22-5). Echocardiographically, fibromas tend to be well demarcated from the myocardium by calcifications (Figure 22-6).³³ These tumors frequently interfere with the conduction pathways. Ventricular arrhythmias are common, and ventricular tachycardia with sudden death is not infrequent. The tumor may occlude or displace the coronary arteries. Patients may present with CHF or angina. Surgical resection is favored even for asymptomatic patients in view of the risk for fatal ventricular arrhythmias.³⁴ Cardiac transplantation has been advocated for septal tumors that are unresectable; however, a subtotal resection achieves excellent late survival.

Figure 22-5 Dissection of ventricular fibroma (Patient 12; patient’s head is at top).

(From Cho JM, Danielson GK, Puga FJ, et al: Surgical resection of ventricular cardiac fibromas: Early and late results, Ann Thorac Surg 76:1933, 2003, by permission.)

Figure 22-6 Transthoracic, parasternal long- (A) and short-axis (B) views of a left ventricular (LV) fibroma (arrows). It is well circumscribed in the posterior free wall. It may cause ventricular arrhythmia, but it does not produce any hemodynamic abnormality. LA, left atrium; RV, right ventricle.

(Reprinted from Oh JK, Seward JB, Tajik AJ: The Echo Manual, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2006, by permission.)

Two vascular tumors, angiomas and pheochromocytomas of the heart (paraganglioma), are rare. Angiomas are found in the interventricular septum, and their vascular nature makes surgery difficult. Primary cardiac pheochromocytomas are located along the atrioventricular groove near the epicardial arteries.³⁵ These tumors arise from neuroendocrine cells. Although cardiac pheochromocytomas became known based on symptoms related to catecholamine secretion, the symptoms are less dramatic than the corresponding adrenal tumors because norepinephrine is not converted to epinephrine in the cardiac tumors. Cardiac pheochromocytomas may go undiagnosed for years while undergoing exploratory laparotomy and multiple diagnostic tests before a cardiac location is considered. If these tumors are nonsecretors of catecholamines, often they are not detected until superior vena cava obstruction, pericardial effusion, or tamponade.³⁶ Fifty percent of these tumors are hereditary, such as in neurofibromatosis or Hippel-Lindau disease. Although surgical excision is curative, total excision may be difficult. Severe intraoperative bleeding is known to occur with these tumors.³⁵ Furthermore, clinicians should be prepared to treat these tumors as catecholamine-secreting tumors that may result in hemodynamic derangements during anesthesia with uncontrolled hypertension, pulmonary edema, and MI.³⁶ Current perioperative management for these tumors has been reviewed.³⁷

Malignant Tumors

Approximately 25% of primary cardiac tumors are malignant,⁵ and 95% of these are sarcomas. They are found infiltrating the RA and causing cavitary obstruction, but may have variable clinical presentations based on the location, causing diagnosis to be elusive. They usually occur between the ages of 30 and 50, preceded by vague symptoms such as dyspnea, but rapidly progressing to death. Angiosarcomas, the most common sarcoma,⁴ are rapidly spreading vascular tumors that arise most often from the RA, appearing near the inferior vena cava with extension to the mediastinum. They occur most commonly in adults and male individuals.⁵ Presenting symptoms include chest pain and dyspnea, progressive CHF, and bloody pericardial effusion.⁹ There are two clinicopathologic forms of the tumor. The first type deposits small tumor in the pericardium or epicardium and is associated with skin lesions or risk factors for Kaposi sarcoma. The second involves large tumor in the RA. Treatment is palliative as the response to chemotherapy and radiation is poor. Resection may be possible, but survival is less than 2 years. Rhabdomyosarcomas are aggressive tumors that have cellular elements that resemble striated muscle. These tumors occur in both sexes equally. They may originate in any chamber of the heart, but in contrast with angiosarcomas, they rarely become diffusely involved with the pericardium. They are bulky and invasive, growing rapidly. Surgical resection is possible, but distant metastasis reduces the chances of success. Chemotherapy and radiation are ineffective.⁵

Echo tends to be less helpful in the management of these patients than it is in patients with benign tumors. It may reveal physiologic complications of the tumor such as cavitary obliteration or valvular regurgitation, and it is helpful in finding associated pericardial effusions and tamponade physiology. However, these tumors have complex anatomy, and the perimeters of the tumor, as well as their involvement in valve apparatuses and coronary anatomy, can be difficult to determine even with TEE. In addition, echo does not image adjacent cardiac structures such as the lung and mediastinum in detail. When echo is combined with other imaging modalities such as CT and MRI, the clinician may obtain the anatomic information needed (from the CT or MRI), as well as the physiologic consequences (from echo).²⁴

Other primary malignant tumors of the heart include malignant fibrous histiocytoma, fibrosarcomas, osteosarcoma, leiomyosarcoma (rarest malignant cardiac tumor), undifferentiated sarcoma, neurogenic sarcoma, and lymphomas. Primary cardiac lymphoma is defined as a non-Hodgkin lymphoma and accounts for about 1% of primary cardiac tumors.³⁸ The prevalence of these tumors has been increasing in part because of AIDS and early detection from imaging advancements such as echo. Lymphomas are generally large masses with extensive infiltration into adjacent areas of the heart from the point of tumor origin. These commonly are located in the RA and RV. These primary tumors are rare, representing less than 2% of all cardiac tumors.³⁹ Treatment involves a combination of chemotherapy and radiation, occasionally extending survival up to 5 years, but the median survival is 1 year. Malignant fibrous histiocytoma, in contrast with other sarcomas, generally is found in the LA. Despite resection, metastasis is common, as well as local recurrence. Surgical excision may be useful to alleviate symptoms but ultimately does not influence the poor survival.⁴⁰

In general, malignant primary cardiac tumors may require a combination of surgery, radiation, and chemotherapy simply to limit cavitary obstruction to blood flow because of rapid growth and metastasis. Local recurrence is more likely to cause death than metastasis.⁴¹ More aggressive approaches for malignant tumors with extensive local disease before metastasis include autotransplantation.³ The heart is removed from the chest cavity and inverted to provide better exposure. Its value is still indeterminate, but no intraoperative deaths have occurred. Although still controversial, orthotopic heart transplantation may be considered for unresectable tumors that involve only the heart, but survival is not extended beyond 1 to 2 years.² The rate of intraoperative death with malignant tumor resection is seven times that of benign resection, and there is twice the morbidity rate.

Most cardiac tumors are rarely associated with airway problems.⁴² Rather, the large pericardial effusions create significant hemodynamic instability and deterioration. Manipulation of these tumors also may exacerbate hemodynamics. If a large pericardial effusion is present before induction of anesthesia, it should be drained. Beyond the standard monitoring used for a cardiac surgical patient, the overall physical status and risk for embolization must be evaluated. Femoral arterial and central venous monitoring are recommended for patients with right atrial tumors. Sudden right-sided tumor embolization may be recognized based on an increased end-tidal carbon dioxide gradient. Left-sided embolization is difficult to assess during anesthesia.

Tumors with Systemic Cardiac Manifestations

Carcinoid tumors are metastasizing neuroendocrine tumors that arise primarily from the small bowel, occurring in 1 to 2 per 100,000 people in the population.⁴³ On diagnosis, 20% to 30% of individuals with carcinoid tumors present with carcinoid syndrome. It is characterized by episodic vasomotor symptoms, bronchospasm, hypotension, diarrhea, and right-sided heart disease attributed to release of serotonin, histamine, bradykinins, and prostaglandins often in response to manipulation or pharmacologic stimulation. Manifestations of carcinoid syndrome occur primarily in patients with liver metastasis and impair the ability of the liver to inactivate large amounts of vasoactive substances.

Initially described in 1952,⁴³ aspects of carcinoid heart disease may occur in 20% to 50% of patients with carcinoid syndrome.^44,45 Carcinoid heart disease may be the initial feature of metastatic carcinoid disease in 20% of patients. The prognosis has improved substantially since the early 1980s for individuals with malignant carcinoid tumors and carcinoid heart disease, but it still causes considerable morbidity and mortality. The median life expectancy is 5.9 years without carcinoid heart disease, but declines to 2.6 years if it is present.⁴⁵ Circulating serotonin levels had been found to be more than twice as high in persons with carcinoid syndrome who develop carcinoid heart disease,⁴⁶ but this is no longer true because most patients receive somatostatin analogs.⁴⁵

Carcinoid heart disease characteristically involves tricuspid regurgitation and pulmonic stenosis and regurgitation resulting in severe right-heart failure (Figure 22-7). Tumor growth in the liver permits large amounts of tumor products to reach the RV without the benefit of first-pass metabolism. Carcinoid plaques composed of myofibroblasts, collagen, and myxoid matrix⁴⁷ are deposited primarily on the tricuspid and pulmonary valves, bringing about immobility and thickening of the valve leaflets, causing the distinctive valvular changes (Figure 22-8). After surgery, 80% of tricuspid valves are observed to be incompetent, with only 20% stenotic, whereas the affected pulmonary valves tend to be equally divided between incompetence and stenosis.⁴⁷ The exact mechanism that causes valve injury is unknown, but high levels of serotonin sometimes are found in those patients with carcinoid heart disease.⁴³ Less than 10% of those with carcinoid heart disease have left-heart involvement, possibly because of inactivation of serotonin in the lungs,⁴⁸ but it may exist with the presence of a bronchial carcinoid or an interatrial shunt.

Figure 22-7 Transthoracic imaging using an apical view in a patient with carcinoid heart disease.

The tricuspid valve (arrow) in both systole (top left) and diastole (top right). Note the thickened tricuspid leaflets move little between systole and diastole, and there is an enormous coaptation defect during systole (top left). Color-Doppler imaging (bottom left) reveals massive tricuspid regurgitation that fills the entire right atrium (RA), which is severely dilated. Bottom right, Continuous-wave Doppler imaging of the hepatic veins reveals systolic flow reversals (deflection of Doppler signal above the baseline during systole) indicative of severe tricuspid regurgitation. RV, right ventricle.

Figure 22-8 A, Two-dimensional echocardiographic systolic image (right ventricular inflow view) demonstrates thickened septal and anterior tricuspid valve leaflets (arrowheads) and enlargement of the right ventricle (RV) and right atrium (RA) in a patient with carcinoid heart disease. B, Color flow Doppler image demonstrates severe tricuspid regurgitation (TR) in the same patient. Note laminar color flow (blue) filling an enlarged right atrium.

(From Otto CM, Bonow RO (eds): Valvular Heart Disease: A Companion to Braunwald’s Heart Disease, 3rd Edition. Philadelphia, Saunders/Elsevier, 2009, P. 339, whith permission.)

Echo features of carcinoid heart disease, particularly of the tricuspid valve, are practically diagnostic of the underlying disease process. The leaflets are thickened and retracted. The appearance of the tricuspid leaflets is often as if the leaflets were curled under (see Figure 22-7). The thickening and retraction result in a large coaptation defect and severe valvular regurgitation. The pulmonic valve may be difficult to image with TTE, but the midesophageal TEE view at 70 to 90 degrees often shows the valve well. With severe tricuspid regurgitation, the RV will dilate and abnormalities of ventricular septal motion may be noted. The thickness of the ventricular wall is usually normal. Doppler imaging of the hepatic veins will show systolic flow reversals consistent with severe tricuspid regurgitation. A careful search for a patent foramen ovale (PFO) should be undertaken because this has implications for left-sided valvular involvement.

Without treatment, median survival with carcinoid heart disease is 11 months.⁴³ A large percentage of patients with carcinoid heart disease are asymptomatic because the disease is mild. Early detection can affect prognosis as progression of cardiac disease, especially to right ventricular failure, increases mortality.⁴⁴ Treatment of the tumor and the malignant carcinoid syndrome does not result in regression of carcinoid heart disease.⁴⁵ Surgery to replace both tricuspid and pulmonary valve with either bioprosthetic or mechanical valve is the only viable therapeutic option.⁴⁹ The decision regarding mechanical or bioprosthetic valve(s) depends on individual risks and concerns.^43,50 The optimal timing to operate is uncertain, but consideration should be given when signs of right ventricular failure appear. Even after surgery, right ventricular dysfunction will persist. Perioperative mortality rate is less than 10%.⁴⁸

Dilated Cardiomyopathy

Formerly referred to as congestive cardiomyopathy or idiopathic cardiomyopathy, DCM is by far the most common of the four cardiomyopathies in adults (60%). The term idiopathic has become less applicable to cardiomyopathies as developments in molecular biology and genetics have provided better insight into the pathogenesis of DCM. In the United States alone, nearly 550,000 individuals are newly diagnosed with CHF, whereas close to 4.6 million receive treatment for it. Even with current management, survival for adults at 1 and 5 years after diagnosis is 76% and 35%, respectively, representing a major health care concern.⁶⁶ Interestingly, diagnosis of DCM in asymptomatic patients occurs in 30% of patients with extended quality of life and survival if medical treatment is initiated.⁶⁷ This would suggest a less-advanced disease process and being more amenable to treatment. Nonischemic causes comprise 25% to 35% of adult patients with left ventricular dysfunction and CHF, of which DCM is a major component.⁶³

DCM has diverse causes, such as viral, inflammatory, toxic, or familial/genetic. It is associated with many cardiac and systemic disorders that influence the prognosis. Approximately 1230 patients with cardiomyopathy were evaluated and grouped according to a specific cause.⁶¹Table 22-3 shows that 50% of patients had common causes for DCM, but 50% were characterized as idiopathic. Currently, there is a greater appreciation for the role of genetic and familial factors in the cause of DCM (Figure 22-9).^64,68,69 Between 10% and 35% of cases of DCM are familial with an autosomal dominant expression.⁶³ Incomplete penetrance may account for differences in disease severity and progression in familial DCM despite sharing identical mutations.⁶⁴ Similarities in clinical course that evoke a common set of molecular and cellular pathways may lead to better therapy in the future despite the many different causes of DCM.

TABLE 22-3 Common Clinicopathologic Diagnoses in 1230 Patients with Initially Unexplained Cardiomyopathy

From Wu LA, Lapeyre AC, Cooper LT: Current role of endomyocardial biopsy in the management of dilated cardiomyopathy and myocarditis. Mayo Clin Proc 76: 1030–1038, 2001.

Figure 22-9 A cardiac myocyte and the molecules that have been implicated in dilated cardiomyopathy. CREB, cyclic AMP response element binding protein; MLP, muscle LIM protein.

(From Leiden JM: The genetics of dilated cardiomyopathy—emerging clues to the puzzle. N Engl J Med 337:1080–1081, 1997, by permission.)

DCM is characterized morphologically by enlargement of right and left ventricular cavities with hypertrophied muscle fibers without an appropriate increase in the ventricular septal or free wall thickness, giving an almost spherical shape to the heart. These hearts are two to three times larger than normal.⁶⁴ The valve leaflets may be normal, yet dilation of the heart has been associated with a regurgitant lesion secondary to displacement of the papillary muscle. Histologic changes are nonspecific and not associated with positive immunohistochemical, ultrastructural, or microbiologic tests. Microscopically, instead of large losses of myocardium, there is patchy and diffuse loss of tissue with interstitial fibrosis and scarring, uncharacteristic of ischemic myocardium.⁶⁴ Degenerative changes are responsible for bundle branch block on the electrocardiogram (ECG).

With DCM, there is more impairment of systolic function even though diastolic function is affected. As contractile function diminishes, stroke volume initially is maintained by augmentation of end-diastolic volume. Despite a severely decreased ejection fraction, stroke volume may be almost normal. Eventually, increased wall stress caused by marked left ventricular dilation and normal or thin left ventricular wall thickness occurs.⁶³ Increasing left atrial size may indicate worsening diastolic dysfunction in these patients, contributing significantly to functional mitral regurgitation.⁷⁰ It is important to expand the diagnosis of mitral regurgitation with echo beyond the left ventricular geometry and mitral orifice because contractility and dyssynchrony are essential for the correct diagnosis. Dilation, combined with valvular regurgitation, compromises the metabolic capabilities of heart muscle and produces overt circulatory failure. Compensatory mechanisms may allow symptoms of myocardial dysfunction to go unnoticed for an extended period. However, the onset of mitral regurgitation signals a poor prognosis as the ventricular function progressively worsens without intervention. The importance of corresponding neurohumoral influences, such as the renin-angiotensin system, on this pathologic process recently was appreciated as a major factor in the appearance of typical signs and symptoms of CHF and formation of therapeutic options (Figure 22-10).^71,72 Additional evidence of cytokine activity and endothelium dysfunction provide a complex interplay of forces leading to circulatory failure. The possibility of blocking this neurohumoral response of CHF pharmacologically has not been fully realized, as early trials have been disappointing.⁷³

Figure 22-10 Impact of pathophysiologic mediators on hemodynamics in patients with heart failure. PCWP, pulmonary capillary wedge pressure; SNS, sympathetic nervous system; SVR, systemic vascular resistance.

(From McBride BF, White CM: Acute decompensated heart failure: A contemporary approach to pharmacotherapeutic management. Pharmacotherapy 23:1002, 2003, by permission.)

Although DCM occurs in children, its presentation is generally in the fourth and fifth decades of life.⁶⁴ The clinical picture of DCM typically includes signs and symptoms of CHF often corresponding to months of fatigue, weakness, and reduced exercise tolerance before diagnosis.⁶² One-third of individuals report chest pain.⁶³ However, the first indication of DCM may be a stroke, arrhythmia, or even sudden death. Increasingly, individuals are presenting for routine medical screening to be informed of cardiomegaly on a routine chest roentgenogram. Symptoms may appear insidiously over a period of years or evolve rapidly after an unrelated illness. Physical signs of DCM, depending on the disease’s progression, include pulsus alternans, jugular venous distention, murmurs of atrioventricular valvular regurgitation, tachycardia, and gallop heart sounds.

A chest roentgenogram demonstrates variable degrees of cardiomegaly and pulmonary venous congestion (Figure 22-11). An ECG may be surprisingly normal or depict low QRS voltage, abnormal axis, nonspecific ST-segment abnormalities, left ventricular hypertrophy, conduction defects, and evidence of atrial enlargement. Atrial fibrillation is common, and about one fourth of patients have nonsustained ventricular tachycardia.⁶² Although the LV is affected, the RV may be spared in some patients, and this finding has been associated with improved survival.⁷⁴ Coronary catheterization usually reveals normal coronary vessels. Coronary angiography also will distinguish between ischemic and idiopathic DCM, a finding that has therapeutic and prognostic implications. An endomyocardial biopsy rarely is valuable to identify the cause of DCM but may be useful to rule out other pathologies with similar presentation to DCM.⁶⁴ The biopsy has no prognostic value or correlation with ventricular function.

Figure 22-11 A, Chest radiograph showing marked cardiomegaly in a 28-year-old man with idiopathic dilated cardiomyopathy. Pulmonary vascularity is within normal limits. B, Left ventriculogram in systole shows marked dilatation. Ao, aorta; LV, left ventricle.

(From Stevenson, LW, Perloff JK: The dilated cardiomyopathies: Clinical aspects. Cardiol Clin 6:187, 1988, by permission.)

Echo is extremely useful in the ambulatory management of patients with DCM. The characteristic 2D findings are a dilated LV with globally decreased systolic function. Indeed, all markers of systolic function (ejection fraction, fractional shortening, stroke volume, and CO) are uniformly decreased.³³ Other associated findings may include a dilated mitral annulus with incomplete mitral leaflet coaptation, dilated atria, right ventricular enlargement, and thrombus in the left ventricular apex (Figure 22-12). In some instances, regional wall motion abnormalities will be present. Color Doppler imaging is useful in assessing the presence or absence of valvular regurgitation. Pulsed-wave and continuous-wave Doppler are used to quantify CO and evaluate filling pressures and pulmonary artery pressures. Well-compensated patients with DCM may have only mild impairment of diastolic function. As the disease progresses and patients become less well-compensated, the left ventricular diastolic filling pattern changes to that of restricted filling. Although systolic function may not change in these patients, the increased filling pressures associated with restrictive left ventricular filling will often worsen their CHF symptomatology.

Figure 22-12 Transesophageal echocardiogram, midesophageal, two-chamber view in a patient with dilated cardiomyopathy.

There is a large amount of the thrombus (arrow) seen in the apex of the left ventricle. In any patient with severe left ventricular dysfunction undergoing an echocardiographic examination, it is important to image the left ventricle as completely as possible to rule out the presence of thrombus.

Management of acute decompensated CHF continues to evolve, but the onset of overt CHF is a poor prognostic indicator for persons with DCM.⁷¹ However, compared with ischemic CHF, patients with nonischemic DCM show greater improvement in symptoms, left ventricular function, and remodeling during more contemporary therapy than in the past.⁷⁵ Treatment revolves around management of symptoms and progression of DCM, whereas other measures are designed to prevent complications such as pulmonary thromboembolism and arrhythmias. The mainstay of therapy for DCM is vasodilators combined with digoxin and diuretics. All patients receive angiotensin-converting enzyme inhibitors to reduce symptoms, improve exercise tolerance, and reduce cardiovascular mortality without a direct myocardial effect.^62,76,77Perhaps more important than the hemodynamic effects, angiotensin-converting enzyme inhibitors suppress ventricular remodeling and endothelial dysfunction, accounting for the improvement in mortality noted with this medication in DCM.⁷⁸ Other afterload-reducing agents, such as selective phosphodiesterase-3 inhibitors like milrinone, may improve quality of life but do not affect mortality, and thus are rarely administered in chronic situations. More recently, spironolactone has assumed a greater role in treatment as mortality rate was reduced by 30% from all causes in patients receiving standard angiotensin-converting enzyme inhibitors for DCM with the addition of spironolactone in a large, double-blind, randomized trial.⁷⁹ Although aldosterone increases sodium retention and reduces potassium loss, it also has been shown to cause myocardial and vascular fibrosis, impair baroreceptor function, and prevent catecholamine reuptake by the myocardium.

Until recently, β-blockers were contraindicated in DCM. In 1982, Bristow et al⁸⁰ found decreased catecholamine sensitivity and β-receptor density in the failing human myocardium, leading to loss of contractility. The association between excess sympathetic activity and the failing heart has been aptly demonstrated.⁸¹ Recently, the dobutamine stress test has been shown to identify changes that reflect increased sympathetic stimulation in the ventricle of asymptomatic to mildly symptomatic patients with DCM.⁸² This finding may aid in the initiation of β-blockers in patients with normal resting parameters. The use of β-blockers in DCM has not only provided symptomatic improvement, but also substantial reductions in sudden and progressive death with NYHA Class II and III heart failure.⁸³ This is especially significant because almost 50% of deaths are sudden.⁸⁴

High-grade ventricular arrhythmias are common with DCM. Approximately 12% of all patients with DCM die suddenly,⁸⁵ but overall prediction of sudden death in an individual with DCM is poor.⁸⁴ Electrophysiologic (EP) testing has a poor negative predictive value that limits its usefulness. The best predictor of sudden death remains the degree of left ventricular dysfunction. Patients who have sustained ventricular tachycardia or out-of-hospital ventricular fibrillation are at increased risk for sudden death, but more than 70% of patients with DCM have nonsustained ventricular tachycardia during ambulatory monitoring.⁷⁷ Furthermore, the prognostic significance of ventricular arrhythmias and response to prophylactic antiarrhythmia therapy in patients with DCM are not well established.

Antiarrhythmic medications are hazardous in patients with poor ventricular function because of their negative inotropic and sometimes proarrhythmic properties. Antiarrhythmic therapy may only be considered in DCM if inducible ventricular tachycardia or symptomatic arrhythmias are present. Class I agents are not indicated because they clearly have demonstrated increased mortality in patients with advanced CHF.⁶² Amiodarone is the preferred antiarrhythmic agent in DCM because its negative inotropic effect is less than other antiarrhythmic medications⁸⁴ and its proarrhythmic potential is lowest.⁸⁶ Counter to most trials of antiarrhythmic prophylaxis, results of a recent large multicenter trial of antiarrhythmic therapy in patients with CHF⁸⁶ demonstrated that amiodarone was associated with a significantly lower mortality rate of 38% compared with 62% without therapy in persons with a higher resting heart rate. Not withstanding these results, implantable defibrillators reduce the risk for sudden death, as well as reducing mortality.^84,85 Recent evidence has indicated that with previous cardiac arrest or sustained ventricular tachycardia, more benefit was gained from an implantable defibrillator.⁸⁷ This was based on a 27% reduction in the relative risk for death attributed to a 50% reduction in arrhythmia-related mortality compared with treatment with amiodarone (see Chapters 4,10, and 25).

Other treatments for DCM include digoxin, which has been reaffirmed as clinically beneficial in two large trials of adults.⁷⁴ The risk for thromboembolic complications is significant in DCM for adults. Patients with moderate ventricular dilation and moderate-to-severe systolic dysfunction have intracavitary stasis and a decreased ejection of blood, so they are likely to receive anticoagulants if any history of stroke, atrial fibrillation, or evidence of intracardiac thrombus exists.

Patients who are resistant to pharmacologic therapy for CHF have received dual-chamber pacing, cardiomyoplasty, left ventricular assist devices, cardiac surgery (nontransplantation) and transplantation in recent years. Cardiac resynchronization therapy with dual ventricular pacing improves NYHA functional class and ejection fraction 6 months after implantation.⁸⁸ Placement of implantable left ventricular assist devices has enabled end-stage patients to reach transplantation or become destination therapy for those in whom transplantation is not an option.⁸⁹ If mitral regurgitation develops in patients with DCM, mitral valve repair or replacement is recommended. The surgery in this high-risk population is safe and improves NYHA classification and survival.⁹⁰ Transplantation can substantially prolong lives, with current survival at 15 years of 50% if younger than 55 years of age⁹¹; however, limited organ availability and drug-related morbidity for those with end-stage DCM looks to future improvements in assist devices and new surgical procedures to provide the best opportunity for increased survival. An example is a new surgical procedure called surgical ventricular restoration that may improve symptoms and cardiac status. It is performed with an arrested heart during CPB. Coronary artery bypass grafting (CABG) is first performed followed by ventriculotomy to insert the mannequin to reshape the ventricle (see Chapters 18 and 27).⁹²

Hypertrophic Cardiomyopathy

Referred to as idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy, and asymmetric septal hypertrophy, among other names, the accepted name is hypertrophic cardiomyopathy (HCM). It is the most common genetic cardiac disease with marked heterogeneity in clinical expression, pathophysiology, and prognosis. The overall prevalence rate for adults in the general population is 0.2%,¹¹⁰ affecting men and women equally. The management continues to evolve with ever-increasing information discovered regarding HCM.

HCM is a primary myocardial abnormality with sarcomeric disarray and asymmetric left ventricular hypertrophy (Figure 22-13). The extent of sarcomeric disarray distinguishes HCM from other conditions.⁵⁹ The hypertrophied muscle is composed of muscle cells with bizarre shapes and multiple intercellular connections arranged in a chaotic pattern.¹¹⁰ Increased connective tissue, combined with markedly disorganized and hypertrophied myocytes, contributes to the diastolic abnormalities of HCM that manifest as increased chamber stiffness, impaired and prolonged relaxation, and an unstable EP substrate that causes complex arrhythmias and sudden death. In contrast with the diastolic function, systolic function in HCM usually is normal or hyperdynamic, but eventually diminishes in the later stages of the disease.

Figure 22-13 A, Hypertrophic cardiomyopathy (HCM) from the long-axis view. Ventricular cavity is small and has pronounced septal and posterior wall thickening. Arrows indicate narrowing of the left ventricular outflow tract caused by the thickened ventricular septum and anterior leaflet of the mitral valve. PW, posterior wall of the left ventricle; VS, ventricular septum. B, Photomicrograph of the myocardium in HCM. There are pronounced disarray and hypertrophy of the individual muscle fibers, resulting in a “whorling” appearance of the muscle fiber. Hematoxylin and eosin stain, original magnification ×165.

(A, From Edwards WD, Zakheim R, Mattioli L: Asymmetric septal hypertrophy in childhood: Unreliability of histologic criteria for differentiation of obstructive and nonobstructive forms. Hum Pathol 8:277, 1977, by permission; B, courtesy of William D. Edwards, MD; from Giuliani ER, Fuster V, Gersh BJ, et al: Cardiology: Fundamentals and Practice. St. Louis, Mosby, 1991, by permission of Mayo Foundation, by permission.)

Besides diastolic dysfunction, the other major abnormality and fundamental characteristic of HCM is myocardial hypertrophy unrelated to increased systemic vascular resistance (SVR). This nonuniform, asymmetric hypertrophy typically occurs in the basal anterior ventricular septum and anterior free wall, with a disproportionate increase in the thickness of the ventricular wall relative to the posterior free wall (Figure 22-13A). Less commonly, the hypertrophy occurs at the apex, lateral wall, or concentrically. The left ventricular wall thickness is the most extensive of all cardiac conditions.¹¹⁰ Heart size may be deceptive because it may vary from normal to more than 100% enlarged. However, chamber enlargement is not responsible for the increase in ventricular mass but rather increases in wall thickness.

HCM is the most common genetic cardiovascular disease inherited in an autosomal dominant manner (1:500 of the general population).⁵⁹ It may be caused by mutations in any of 10 genes; however, 3 genes that encode proteins of the cardiac sarcomere predominate in frequency.¹¹¹ The similarity of the genes accounts for the many different expressions of HCM while resembling one disease entity. Patients without a family history of HCM may have sporadic gene mutations or simply a mild form of the disease. DNA analysis of mutant genes is the most definitive method to establish the diagnosis. The phenotype appears not only to depend on the mutation but also other modifier genes and environmental factors.^111,112 Not all patients who possess a gene for HCM will manifest clinical features of the disease, reflecting incomplete genetic expression.¹¹⁰ A preclinical diagnosis in a patient without symptoms is possible with gene testing not routinely performed now or used to establish a treatment strategy.

HCM is unique for its range of clinical presentations from infancy to 90 years of age. Although major referral centers describe a disease with severe symptomatology, many elderly adults with mild-to-asymptomatic disease were unaccounted for, resulting in an actual annual mortality rate for HCM closer to 1% per year than previously reported to be 3% to 6% per year.¹¹⁰ Even left ventricular outflow tract (LVOT) obstruction may be tolerated longer than initially believed. Most patients with HCM are asymptomatic or have mild symptoms that progress slowly or not at all.⁶³

Symptoms of HCM are nonspecific and include chest pain, palpitations, dyspnea, and syncope. Dyspnea occurs in 90% of patients secondary to diastolic abnormalities that increase filling pressures causing pulmonary congestion. Syncope occurs in only 20% of patients, but 50% may have presyncopal symptoms. The physical examination is sometimes unreliable because classic physical findings are associated with LVOT obstruction that is not present in all patients; however, a recent study observed prospectively 320 patients with HCM and their gradients.¹¹³ They found that 37% of patients had LVOT obstruction at rest and another 33% only with provocation. Symptoms usually appear in the second or third decade, but HCM is not a static disease, and left ventricular hypertrophy can occur at any age and increase or decrease dynamically throughout the person’s life.¹¹⁰ The ECG is abnormal in most individuals showing increased QRS voltage, ST-segment and T-wave abnormalities, QRS axis shift, and left ventricular hypertrophy with strain pattern. There is little correlation between ECG voltages and the degree of left ventricular hypertrophy.¹¹⁰ A chest roentgenogram may show left atrial enlargement or be normal.

Echo is the modality of choice for the evaluation of HCM. Two-dimensional TTE usually allows the clinician to characterize the morphology of the disease and location of the hypertrophy. Doppler and color-flow imaging have typical appearances in HCM. Continuous-wave Doppler is used to quantify the gradient across the LVOT. The Doppler signal has a unique “dagger-shaped” appearance (Figure 22-14). The LVOT Doppler signal typically is obtained with an apical position of the transducer during TTE or from a deep transgastric view when TEE is utilized. If the LVOT gradient is less than expected, provocative maneuvers should be utilized in an effort to demonstrate an increased gradient. A Valsalva maneuver, by decreasing preload and ventricular filling, and inhalation of amyl nitrite are both noninvasive techniques that can be used in the conscious patient (see Figure 22-14). Mitral regurgitation usually accompanies LVOT obstruction when the obstruction is severe or symptomatic. The narrowing of the LVOT by septal hypertrophy necessitates an increase in flow velocity through the LVOT. This increase in flow velocity draws the anterior leaflet of the mitral valve into the LVOT, called the Venturi effect. The mitral leaflet and apparatus subsequently cause obstruction of flow through the LVOT, as well as mitral regurgitation. Temporally, mitral regurgitation occurs after LVOT obstruction: ejection → obstruction to left ventricular outflow → mitral regurgitation. The jet of mitral regurgitation typically is directed posterolaterally (Figure 22-15). It is important to note that if the mitral regurgitant jet is not posterolateral, there likely is another component to the mitral regurgitation such as mitral valve prolapse (MVP) or ruptured chordae. This has important ramifications in terms of planning a surgical repair. The diastolic filling pattern associated with HCM is that of severely impaired myocardial relaxation secondary to hypertrophy.¹¹⁰

Figure 22-14 Continuous-wave Doppler spectra obtained from the apex demonstrating dynamic left ventricular outflow tract (LVOT) obstruction. Note the typical late-peaking configuration resembling a dagger or ski slope (arrows). The baseline (left) velocity is 2.8 m/sec, corresponding to the peak LVOT of 31 mm Hg (4 × 2.8²). With the Valsalva maneuver (right), the velocity increased to 3.5 m/sec, corresponding to a gradient of 55 mm Hg.

(From Oh JK, Seward JB, Tajik AJ: The Echo Manual, 3rd ed. Philadelphia, 2006, Lippincott Williams & Wilkins, by permission.)

Figure 22-15 Transesophageal long-axis view of the aortic valve and left ventricular outflow tract (LVOT) in a patient with hypertrophic obstructive cardiomyopathy (HCM).

Left, Two-dimensional image. The septum is thickened (arrow). The aortic valve is opening indicating systole, and both of the mitral valve leaflets have been drawn into the LVOT. Right, Classic color Doppler image of a patient with HCM is displayed. Aliasing of the Doppler spectra begins at the base of the heart, the site of the septal hypertrophy (yellow arrow), and becomes more severe in the LVOT (white arrow). The mitral regurgitation signal (red arrow) is directed posterolaterally. The three color signals form a Y shape. AO, aorta; LA, left atrium; LV, left ventricle.

Intraoperative TEE is essential in the care of patients undergoing septal myectomy.¹¹⁴ Before incision, TEE can identify the location of hypertrophy in relation to the aortic annulus, as well as the thickness of the ventricular septum, which assists the surgeon in planning the location and depth of the myectomy. The mitral valve should be closely evaluated for abnormalities that may contribute to mitral regurgitation, particularly if the regurgitant jet is directed centrally or anterior. After the myectomy, TEE is used to assess the degree of residual mitral regurgitation and evidence of continued systolic anterior motion (SAM) and LVOT obstruction. The ventricular septum also must be closely evaluated for evidence of shunting via an iatrogenic ventricular septal defect (VSD). It is common to see small shunts into the area of the LVOT from transection of coronary vessels at the site of the myectomy (Figure 22-16). It is important that these are not confused with shunting from a VSD. When an iatrogenic VSD occurs, the expected shunt would be from the LV into the RV, as opposed to the flow observed into the LV from transection of septal coronary artery branches. In addition, shunting through a VSD would be expected to occur predominantly during systole, whereas flow into the LV from septal perforators is predominantly during diastole.

Figure 22-16 Transesophageal image from a patient after a septal myectomy for hypertrophic obstructive cardiomyopathy.

The probe is in the midesophagus in a modified long-axis view. Color Doppler imaging reveals two jets of blood flow into the left ventricular outflow (arrows) tract from small coronary perforators that were transected during the myectomy. It is important that these jets of blood flow are not confused with a ventricular septal defect. LA, left atrium; LV left ventricle.

Angiography may show a left ventricular pressure gradient, decreased ventricular volume, and increased left ventricular end-diastolic pressure. Coronary artery diseases may be absent angiographically, but thallium redistribution scans demonstrate that HCM patients may experience myocardial ischemia often associated with atypical chest pain, not relieved with nitrates.¹¹⁵ Blunted coronary perfusion despite angiographically normal coronary arteries is characteristic of a coronary microvascular dysfunction that increases the risk for ischemia, especially in the subendocardium. More recently, the degree of LVOT obstruction and wall stress were found to exacerbate microvascular dysfunction.¹¹⁶ This may have implications for treatments that reduce left ventricular mass and wall stress instead of increasing diastolic filling time with medications such as β-blockers and calcium channel blockers, and partially explain the benefit of myectomy. Thallium abnormalities may represent relatively underperfused myocardium with abnormal intramyocardial coronary arteries that exist in patients with HCM. Abnormal coronary vasodilation in both nonhypertrophied and hypertrophied myocardium occur in HCM.¹¹⁷ This suggests that impaired coronary vasodilation has a major role in the pathogenesis of HCM and is not secondary to only myocardial hypertrophy. However, a mismatch between myocardial oxygen demand resulting from systolic and diastolic abnormalities, increased ventricular mass, and coronary circulation may exacerbate myocardial ischemia. Thus, myocardial death and scarring may then serve as a substrate for ventricular tachycardia and fibrillation.¹¹⁰

Two thirds of individuals with LVOT obstruction will become severely symptomatic, and there is a 10% mortality rate within 4 years of diagnosis. The LVOT is narrowed from septal hypertrophy and anterior displacement of the papillary muscles and mitral leaflets, creating a dynamic left ventricular outflow obstruction. Elongation of the mitral leaflets results in coaptation of the body of the leaflets instead of the tips. The part of the anterior leaflet distal to the coaptation is subjected to strong Venturi forces that provoke SAM, mitral septal contact, and ultimately, LVOT obstruction (Figure 22-17).¹¹¹ However, studies suggest that the mechanism of SAM is more complex. SAM can occur before the opening of the aortic valve and the generation of maximum Venturi effect because of the position of the mitral leaflets on the LVOT, reflecting its importance in SAM compared with traditional explanations. Longitudinal flow in the ventricle may push the mitral valve into the LVOT.¹¹⁸ SAM of the anterior leaflet also may cause mitral regurgitation that is unlike that seen with intrinsic structural abnormalities of the valve. The onset and duration of mitral leaflet-septal contact determine the magnitude of the gradient and the degree of mitral regurgitation. The pressure gradient between the aorta and LV (Figure 22-18) is worsened by decreased end-diastolic volume, increased contractility, or decreased aortic outflow resistance (Figure 22-19).¹¹⁹ The cavity of the LV often is small in those with severe gradients (Figure 22-20).

Figure 22-17 Depiction of the modern concepts of the mechanism of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. In early systole (bottom left), abnormal flow around the hypertrophied septum pushes the mitral valve in the outflow tract and results in obstruction and mitral valve regurgitation (bottom right).

(From Ommen SR, Shah PM, Tajik AJ: Left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: Past, present and future. Heart 94:1276–1281, 2008, by permission.)

Figure 22-18 Simultaneous left ventricular (LV) and aortic pressure tracings from a patient with muscular subaortic stenosis (resting obstruction).

(From Wigle ED, Sasson Z, Henderson MA, et al: Hypertrophic cardiomyopathy: The importance of the site and extent of hypertrophy: A review. Prog Cardiovasc Dis 28:1, 1985, by permission.)

Figure 22-19 Interventions that change the outflow gradient in hypertrophic cardiomyopathy (HCM), with resultant change in intensity of the systolic murmur in HCM. Outflow gradient is affected by changes in afterload, preload, and contractility. Ao, aorta; LA, left atrium; LV, left ventricle; MV, mitral valve; PW, posterior wall; VS, ventricular septum.

(From Giuliani ER, Fuster V, Gersh BJ, et al: Cardiology: Fundamentals and Practice. St. Louis, Mosby, 1991, by permission of Mayo Foundation.)

Figure 22-20 Midventricular hypertrophy.

Cross-sectional slices of the heart from a patient who was shown, by hemodynamic, angiographic, and echocardiographic techniques, to have midventricular obstruction. The site of the obstruction was at the level of the papillary muscles, where there was massive hypertrophy (second slice from left). The slice at left is from the base of the heart, and the two slices at the right are from the apex. The apex of the left ventricle was the site of extensive myocardial infarction and aneurysm formation that was evidenced in life by a dyskinetic apical chamber on angiography and by persistent ST-segment elevation in leads V₄ to V₆ on the electrocardiogram. The coronary arteries revealed no significant luminal narrowings. The patient died of intractable ventricular arrhythmias.

(From Wigle ED, Rakowski H, Kimball BP, et al: Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation 92:1680, 1995, by permission.)

Dynamic LVOT obstruction is not limited to HCM but may occur in cardiac tamponade or acute MI.¹¹⁹ It may be seen in the immediate postoperative period after aortic valve replacement for aortic stenosis or mitral valve repair. Importantly, dynamic pressure gradients do not necessarily correlate with symptoms of HCM. Significant functional limitation, disability, and sudden death may all occur even with no gradient. However, gradients exceeding 30 mm Hg are usually of physiologic and prognostic importance in HCM patients.¹¹¹ The severity of symptoms is not worse once a gradient exceeds 30 mm Hg. LVOT obstruction is an independent predictor of death in HCM.¹²⁰ Because LVOT obstruction is likely to be associated with increased wall stress, myocardial ischemia, cell death, and eventual fibrosis, treatment to relieve it is desirable.

The clinical course and treatment of HCM are best approached in relation to subgroups: sudden death, CHF, and atrial fibrillation with embolic stroke (Figure 22-21). Sudden death increases the annual mortality rate from 1% to 5% overall.¹¹⁰ Often these patients are asymptomatic or mildly symptomatic and constitute a small part of the HCM population. Sudden death is not age restricted but occurs more commonly in younger individuals, frequently in association with physical exertion. HCM is the most common cause of sudden death in otherwise healthy young individuals, reaching up to 6% per year in those 20 to 30 years of age.¹²¹ Risk stratification for sudden death is useful now that it has been found that ventricular tachycardia or ventricular fibrillation is the culprit.^110,122 High-risk individuals are more likely to have these characteristics: diagnosis by 30 years of age, prior cardiac arrest, symptomatic ventricular tachycardia per Holter monitor, and family history of sudden death or syncope.¹²¹ Additional risk factors include identification of a high-risk mutant gene, unexplained syncope, abnormal blood pressure with exercise, resting LVOT obstruction of 30 mm Hg or greater, atrial fibrillation, and even coronary artery disease.^111,121 Two or more risk factors are associated with a risk for sudden death of 4% to 5% per year.

Figure 22-21 Hypertrophic cardiomyopathy (HCM) clinical subgroups are not necessarily mutually exclusive; overlap or progression from one subgroup to another may occur (thin solid and dashed arrows). Most patients with HCM who are at high risk for sudden death or who experience development of atrial fibrillation are initially in the “None or Mild Symptoms” clinical subgroup. Asterisk indicates that patients with a positive genotype and negative phenotype may subsequently show morphologic conversion to the HCM phenotype with left ventricular hypertrophy (usually in adolescence, but also in midlife or later). Dagger indicates that drug therapy may include β-blockers, calcium channel blockers (particularly verapamil), disopyramide, as well as diuretic agents. Double dagger indicates that for major interventions, obstructive HCM is generally regarded as a left ventricular outflow gradient of approximately 50 mm Hg at rest or with provocative maneuvers; in this context, nonobstructive HCM is regarded as a left ventricular outflow gradient of less than approximately 30 to 50 mm Hg at rest, as well as with provocative maneuvers. Width of the arrows from the overall HCM population represent the approximate relative proportion of patients with HCM within each major clinical subgroup.

(Originally adapted from Spirto et al: The management of hypertrophic cardiomyopathy. N Engl J Med 336:775–785, 1997, by permission of the Massachusetts Medical Society; reprinted with permission from Maron BJ: Hypertrophic cardiomyopathy: A systematic review JAMA 287:1313, 2002.)

The value of EP testing as it relates to prediction of sudden death is mixed.^111,123,124 Recently, routine risk stratification with EP testing was abandoned in HCM patients.¹¹¹ Extreme left ventricular wall thickness has been associated with greater incidence of spontaneous ventricular arrhythmias and sudden death. Myocardial ischemia also appears to be related to sudden death in younger patients.¹²⁵ In the future, genotyping may be able to reliably define the risk for sudden death, but currently there is no ability to screen patients to determine risk stratification with clinical gene tests for characteristics such as sudden death.¹²⁶ Septal myectomy reduces the risk for sudden death in patients compared with those with LVOT obstruction and no surgery and those with nonobstructive HCM. The mechanism for this improved survival is indeterminate.¹²⁷

The only effective modality to prevent sudden death associated with HCM currently is the implantable cardioverter-defibrillator. Pharmacologic therapy for prevention of sudden death recently was shown to reduce symptoms but not risk for sudden death.¹²⁸ Symptomatic patients or those with a positive EP test appear to benefit from implantable cardioverter-defibrillator placement. A retrospective study found that 25% of high-risk cohorts required termination of lethal ventricular arrhythmias and 60% experienced some type of intervention by an implantable cardioverter-defibrillator.¹²² The implantable cardioverter-defibrillator has been shown in a randomized, prospective trial to be superior to drug therapy.¹²⁹ However, a long-term follow-up of patients receiving implantable cardioverter-defibrillators for HCM has shown a worrisome rate of inappropriate (5.3%/year) versus appropriate (4%/year) shocks.¹³⁰ The overall incidence rate of device complications was concerning at 36% during a 5-year period. Even though the implantable cardioverter-defibrillator saves lives in high-risk patients, the risk for complications should factor into the decision to implant it. Amiodarone is no longer the first line of antiarrhythmic therapy for patients at risk for sudden death as previous studies were nonrandomized case studies.⁶³

Another subgroup is patients with CHF who develop progressive symptoms with preserved systolic function but quickly advance to end-stage CHF with impaired systolic function.¹¹¹ Symptoms are primarily attributed to the diastolic abnormality; therefore, symptomatic relief is achieved by improving ventricular relaxation. Medications with negative inotropic effect generally are successful in relieving symptoms of exercise intolerance and dyspnea associated with CHF,¹³¹ but symptoms may return in up to 60% of pharmacologically treated patients.¹³² In general, β-blockers have been a mainstay of therapy for years in adults and are preferred over calcium channel blockers. High doses of β-blockers usually are needed for therapeutic value. Verapamil may be given if β-blockers are not tolerated or ineffective, but symptomatic improvement may be less than 50%.¹³² The combination of β-blockers and calcium channel blockers has not proven beneficial. β-Blockers relieve symptoms of angina and dyspnea and improve exercise tolerance by limiting the gradient associated with exercise. The gradient is not reduced at rest by these medications.¹¹¹ Other beneficial effects of β-blockers include heart rate reduction, lower myocardial oxygen demand, and longer diastolic filling times, but diastolic function is neither improved nor is long-term survival prolonged. Verapamil improves diastolic function and ventricular relaxation, causing improved filling and decreased obstructive features in 50% of HCM patients. Patients with obstructive symptoms may worsen with calcium channel blockers that contain strong vasodilator properties. Disopyramide, a negative inotrope that alters calcium kinetics and produces a vasoconstrictor effect, has been recommended instead of calcium channel blockers in obstructive HCM.¹¹¹ Disopyramide is the most effective agent to reduce LVOT obstruction and gradient, as well as relieve symptoms.¹³³ Combined with β-blockers, disopyramide prolongs exercise times more successfully than verapamil.

Surgical correction of HCM is directed primarily at relieving symptoms of LVOT obstruction in the 5% of patients who are refractory to medication.¹¹¹ In general, these are individuals with subaortic gradients in excess of 50 mm Hg with or without provocation and frequently associated with severe CHF.^63,110 A myotomy-myectomy through a transaortic approach is the primary method used to relieve the obstruction (Figure 22-22). The muscle is excised from the proximal septum extending just beyond the mitral valve leaflets that widens the LVOT. Currently, the classic Morrow technique has been replaced by a more extensive resection that is described in more detail elsewhere.^133,134 This is a technically challenging operation because of the limited exposure and precise area to excise the muscle. It usually is reserved for centers with considerable experience with myectomy. When myectomy is successful, the LVOT is widened and SAM, mitral regurgitation, and outflow gradient are all decreased. Mitral valve repair or replacement has accompanied myectomy when there is coexistent primary mitral valve structural abnormalities, but mitral valve replacement is not indicated for treating LVOT obstruction alone.¹¹⁸ If the valve is not repaired during myectomy, incomplete or temporary relief of obstruction may occur. Recently, Wan et al¹³⁵ described the use of mitral valve repair in those with LVOT obstruction and degenerative mitral valve disease. Mitral valve repair was effective compared with replacement with low early mortality and successful treatment of both obstruction and mitral valve regurgitation. Mitral valve replacement is rare.

Figure 22-22 Two operative approaches for performing septal myectomy in obstructive hypertrophic cardiomyopathy. A, Typical outflow tract morphology with predominant basal septal hypertrophy and subaortic obstruction caused primarily by systolic anterior motion of the mitral valve. Endocardial thickening at the line of apposition of the anterior mitral leaflet to the septum (friction lesion) can be seen (right insert). A standard rectangular myectomy trough (Morrow procedure) is created from 1 cm below the aortic valve apically to a point beyond the line of mitral-septal contact and intraventricular obstruction, allowing relief of the outflow tract gradient and preservation of sinus rhythm (left insert). B, In the presence of muscular midcavity obstruction caused by anomalous papillary muscles with direct insertion into the mitral valve or to extensive diffuse septal hypertrophy extending to the bases of the papillary muscles, a much more substantial myectomy is performed by combining the standard operation with an extended midventricular resection. The apical portion of the myectomy trough is much wider and includes the distal third of the right side of the septum.

(From Dearani JA, Ommen SR, Gersh BJ, et al: Surgery insight: Septal myectomy for obstructive hypertrophic cardiomyopathy—the Mayo Clinic experience. Nat Clin Pract Cardiovasc Med 4:503–512, 2007, by permission.)

Surgery provides persistent, long-lasting relief from symptoms that exceeds any form of current medical treatment.¹³¹ Five years after myectomy, 85% of patients have improved enough to advance one NYHA functional class.¹³⁶ The concomitant reduction in left atrial size may partially account for the lower incidence of atrial fibrillation after myectomy.¹¹¹ Septal myectomy results in reduction in left ventricular mass that exceeds the myocardium resected over time, indicating a relief of the pressure overload.¹³⁷ Myectomy also is associated with a mortality rate of less than 1% in major institutions.¹³² This low mortality rate is even more noteworthy because surgical patients usually have more severe disease than those treated medically. Long-term survival rates at 1, 5, and 10 years are 98%, 96%, and 83%, respectively. Surgical patients have an overall survival rate that is equivalent to the age- and sex-matched general population.¹²⁷ Complications of myectomy such as complete heart block or septal perforation (0% to 2%) are rare.¹³³ Similarly, recurrence of LVOT gradient or SAM requiring repeat myectomy is less than 2%.¹¹⁸

Surgery is not recommended for HCM without an obstructive component or if the individual is asymptomatic to mildly symptomatic for the following reasons: (1) Better survival with surgery versus medical therapy is not established; (2) operative mortality may exceed the risk of HCM in mildly affected patients; (3) LVOT obstruction may be compatible with longevity in selected individuals; and (4) no evidence exists that surgery halts the progression of HCM to end-stage.¹¹¹ End-stage patients with nonobstructive HCM who have severely reduced systolic function are effectively treated with heart transplantation with 7-year survival rate of 90% that compares equally to those with DCM who require transplantation.¹³⁸ Medical treatment for asymptomatic HCM patients is not clearly indicated.

Possible alternatives to surgery have included dual-chamber pacing and percutaneous alcohol septal ablation. Previously, atrioventricular sequential pacing had been shown to decrease subaortic gradients, possibly by causing abnormal septal motion, and thus was considered a possible treatment even though the mechanism has not been proved.¹³¹ Pacing has become the most rigorously evaluated treatment of all therapies for HCM. A series of nonrandomized and randomized studies have shown reductions in the LVOT gradient and improvement in symptoms, but others have found no differences in gradient, NYHA class, quality-of-life score, exercise duration, or maximal oxygen uptake, reflecting a significant placebo effect.¹³⁹ Within groups, there appear to be responders, but no variables that identified these patients.¹¹⁸ Consequently, the optimal use of pacing in HCM requires continued reevaluation.¹³¹ When pacing was compared with surgical therapy, LVOT gradient was reduced to less than 20 mm Hg in only 26% of patients, compared with more than 90% of surgical patients,¹¹⁸ creating drastically fewer indications for pacing. Furthermore, symptoms were improved in all patients with surgery compared with only 50% with pacing. The role of pacing has been relegated to one in which there are absolute contraindications to other therapies.

Septal ablation with alcohol is a nonsurgical myocardial reduction first attempted in 1994 based on interruption of blood supply to the interventricular septum, causing infarction. This resulted in reduced septal thickness and LVOT modeling with resolution of symptoms in HCM.¹⁴⁰ Alcohol is administered through an angioplasty balloon to the first major septal perforator of the left anterior descending coronary artery. The success rate has been good as indicated by a recent systematic review of ablation incorporating 42 studies and nearly 3000 patients.¹⁴¹ The study showed effective gradient reduction and improvement in NYHA class comparable with myectomy 12 months after ablation. However, 20% of patients required a second procedure, and some even required myectomy after alcohol ablation. A retrospective review of 375 patients who underwent alcohol ablation identified 20 patients who underwent subsequent surgical myectomy for recurrent dynamic LVOT obstruction.¹⁴² The surgery was successful in all of the failed ablation patients, indicating myectomy as rescue therapy for failed alcohol septal ablation. There is concern about the incidences of complications and mortality accompanying alcohol ablation. Annual mortality rate with alcohol septal ablation in the best centers in the United States is 2%, with Canada reporting 4% to 10%.¹¹⁸ Besides mortality, the incidence of nonfatal complications is a concern compared with surgical myectomy. Heart block necessitating pacemaker placement has been reported in between 11% and 38% of patients.¹⁴³ The toxic effect of alcohol on both the coronary circulation and the myocardium has the potential to generate morbidity.¹³¹

Perhaps the greatest concern is that fewer surgeons are learning and performing myectomy because of the steep learning curve, but the relative ease of the septal ablation in comparison with myectomy has greatly increased the individuals performing ablation. Because the longest follow-up studies for alcohol ablation are 2 years, long-term benefit for this procedure is lacking. Retrospective studies do not permit any conclusion regarding the superiority of septal ablation with myectomy, so clinicians are awaiting a long-term comparative study to define its role in HCM. Because management of HCM continues to be made based on experience and consensus to a large degree, surgical myectomy remains the first option for HCM with ablation as an alternative, especially if serious comorbidity exists.¹¹¹ Treatment will continue to evolve as the proper patient selection and long-term effects are evaluated.

Restrictive Cardiomyopathy

RCM has included such entities as amyloidosis and eosinophilic endomyocardial disease. The 1995 WHO guidelines defined RCM as “restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness.”⁵⁹ Instead of being classified according to morphologic criteria, as are HCM and DCM, RCM is characterized by function. It may appear in the final stages of other cardiac conditions. Although a clinically challenging diagnosis to make, it is important to distinguish “restrictive” physiology from “constrictive” because management and treatment are decidedly different. Restrictive/constrictive physiology is not solely limited to RCM, but occurs in mitral stenosis, tricuspid stenosis, and aortic stenosis.

RCM is much less frequent than DCM or HCM.¹⁴⁸ It is classified as myocardial (infiltrative, noninfiltrative, and storage) or endomyocardial (Box 22-1) according to cause. The compliance of the “restrictive” myocardium is reduced by one of these processes: extracellular infiltration, intracellular accumulation of abnormal substances, inflammation, or endocardial disease.^148,149 Restrictive myocardial disorders are characteristically atypical in presentation and hemodynamics at times, complicating perioperative management. With idiopathic RCM, the cause is entirely unknown and lacks any identifiable histopathologic distinctiveness. Its occurrence is quite rare, with few actual series in adults.¹⁵⁰ More extensive reviews of the many types of RCM are available.^150–152

Systolic function is minimally affected in RCM. Diastolic dysfunction is evident by abnormalities of ventricular relaxation and compliance. Impaired ventricular relaxation occurs before abnormal compliance. Poor compliance of the ventricle causes rapid filling in early diastole and the characteristic ventricular diastolic waveform of dip-and-plateau (square-root sign; Figure 22-23). However, the characteristic dip-and-plateau pattern may be absent in 50% of affected individuals because it depends on the degree of impaired ventricular relaxation and the level of atrial driving pressure.¹⁵¹ The atrial pressure waveform will have the appearance of an M or W pattern because of the rapid y descent combined with a slightly greater x descent. The rapid y descent is due to the rapid early decline of the atrial pressure corresponding to the early diastolic ventricular filling. Filling early in diastole is accentuated and impeded during the rest of diastole because of reduced ventricular distensibility. Pressure in the ventricle increases precipitously in response to small volume. Once ventricular filling is restricted, the prognosis is much worse. Both ventricles appear thick with small cavities. In contrast, the corresponding atria appear dilated despite normal left ventricular volumes. Cardiomegaly or ventricular dilation should not exist. The left-sided pulmonary venous pressures usually exceed the right-sided venous pressures by 5 mm Hg. The pulmonary artery systolic pressure also may be increased to 50 mm Hg.

Figure 22-23 Intracardiac pressure tracings from a patient with idiopathic primary restrictive cardiomyopathy.

Top, Right ventricular (RV) and right atrial (RA) tracings with a typical diastolic square-root configuration in the RV tracing and a prominent y descent in the early diastolic period of the right atrial tracing. Bottom, Simultaneous left ventricular (LV)-RV pressures and LV-RA pressures, showing a square-root configuration in the LV tracing and equalization of pressures during diastole in the three chambers. FA, femoral artery.

(From Giuliani ER, Fuster V, Gersh BJ, et al: Cardiology: Fundamentals and Practice. St. Louis, Mosby, 1991, by permission of Mayo Foundation.)

Because one or both ventricles may be involved, symptoms may predominate as right- or left-sided. The increased filling pressures that occur in early diastole of both ventricles lead to symptoms of right-sided failure manifested by increased venous pressures, peripheral edema, and ascites, or left-sided failure manifested by CHF, progressive dyspnea, and orthopnea. Both groups of symptoms may occur separately or simultaneously. Insidious onset of fatigue and exertional dyspnea are common. Symptoms and signs should be present without evidence of cardiomegaly. The jugular venous pulse fails to fall during inspiration and may even rise (Kussmaul’s sign).¹⁵² Pulsus paradoxus is infrequent and nonspecific. The liver may be enlarged and actually pulsatile. The chest roentgenogram is nondiagnostic. Pulmonary congestion and a normal or smaller than anticipated heart size suggest a diagnosis of RCM. Thromboembolic complications are common with the initial presentation of the disease. The ECG may reflect abnormalities of depolarization such as bundle branch block, low voltage, and QR or QS complexes, but these are not specific to RCM and rarely are useful to distinguish RCM from constrictive pericarditis (CP). ECG evidence of biatrial enlargement may be present.¹⁴⁹

It is important to distinguish between RCM and CP because management of the two diseases is very different. Important distinguishing features of CP and RCM are listed in Table 22-4. Both conditions have rapid and early diastolic filling with increased filling pressures and normal filling volumes. In RCM, the impediment to filling is usually an infiltrative process involving the myocardium rather than the pericardium. Although not an absolute sign, the right ventricular and left ventricular end-diastolic pressures are increased and equal with constrictive physiology, whereas in RCM, end-diastolic pressure is usually 5 mm Hg greater on the left than on the right side because of the unequal compliance between the two ventricles.^150,153 Unfortunately, symptoms and physical signs do not reliably discriminate between RCM and CP.

TABLE 22-4 Differentiation of Pericardial Constriction versus Myocardial Restriction

CT, computerized axial tomography; LAP, left atrial pressure; MRI, magnetic resonance imaging; RAP, right atrial pressure.

From Hancock EW: Cardiomyopathy: Differential diagnosis of restrictive cardiomyopathy and constrictive pericarditis. Heart 86:343–349, 2001; and Chatterjee K, Alpert J: Constrictive pericarditis and restrictive cardiomyopathy: Similarities and differences. Heart Failure Monit 3:118–126, 2003.

Advances in echo and other noninvasive methods have been used to try to reliably discriminate between pericardial disease and RCM. The usual 2D echo findings are those of normal size, thickness, and preserved systolic function of the ventricles with enlargement of the atria (Figure 22-24). Classic Doppler findings are described in Table 22-5. Doppler findings may indicate the severity of RCM once the diagnosis is certain. Because the pericardium is responsible for CP and a noncompliant ventricle for RCM, some differences exist between RCM and CP regarding M-mode, 2D, and Doppler examinations.¹⁵⁴ A pericardial thickness of 3 mm measured by echo is indicative of CP. But overall, Doppler and echo have insufficient sensitivity and specificity to provide a clinically significant differentiation between RCM and CP. More recently, tissue Doppler imaging has demonstrated some success in providing differentiation between RCM and CP by measuring E velocity to determine ventricular relaxation with 89% sensitivity and 100% specificity.¹⁵⁵ Other noninvasive methods that may be helpful are the CT to determine the thickness of the pericardium and the MRI to diagnose infiltrative processes such as amyloidosis.¹⁴⁹

Figure 22-24 Apical four-chamber view of a typical case of restrictive cardiomyopathy with normal left ventricular (LA) size, normal LV ejection fraction, and marked biatrial enlargement. B, Patients with restrictive cardiomyopathy are frequently in atrial fibrillation. A mitral inflow pulsed-wave Doppler velocity recording shows a deceleration time (DecT) of 170 milliseconds and mild variation in E velocities. C, Mitral annulus tissue velocity recording demonstrating E′ of 8 cm/sec and delayed relaxation (arrow), and a′ related to atrial fluttering or fibrillating motion. E′, mitral annulus early diastolic velocity; E/E′, 100/8 = 13, consistent with a mild increase in filling pressures; LA, left atrium; RA, right atrium; RV, right ventricle; S′, systolic velocity of the mitral annulus.

(From Oh JK, Seward JB, Tajik AJ: The Echo Manual, 3rd ed. Philadelphia, 2006, Lippincott Williams & Wilkins, by permission.)

TABLE 22-5 Doppler and Echocardiographic Features Differentiating Restrictive Cardiomyopathy and Constrictive Pericarditis

E′, early peak velocity; IVRT, isovolumic relation time; RVSP, right ventricular systolic pressure; S/D, systolic/diastolic; Vp, propagation velocity.

From Tam JW, Shaikh N, Sutherland E: Echocardiographic assessment of patients with hypertrophic and restrictive cardiomyopathy: imaging and echocardiography. Curr Opin Cardiol 17:474, 2002.

Cardiac catheterization still is performed to differentiate between RCM and CP. During catheterization, increased left and right venous pressures with large A and V waves may be observed in RCM (see Figure 22-23). It is not uncommon to see right atrial pressures of 15 to 20 mm Hg. The ventricular pressure curve may display the diastolic dip-and-plateau pattern (square-root sign) as described previously. Recently, more advanced catheterization criteria for differentiation of RCM and CP have been devised.¹⁵⁶ This new measurement, systolic area index, assesses the dynamic changes in ventricular pressure area during inspiration and expiration to distinguish CP from RCM. In CP, there is a dissociation between intrathoracic and intracardiac pressures that causes decreased filling in the LV during inspiration. The constricting pericardium also causes increased ventricular interaction so that the RV is better filled during inspiration. This new index has 97% sensitivity and 100% predictive accuracy in patients with documented CP compared with older catheterization indices that generated predictive accuracy for RCM and CP that was less than 75%.

Endomyocardial biopsy may differentiate RCM from CP. The biopsy in RCM rarely is normal compared with CP. Although a biopsy may identify specific causes of restrictive physiology,¹⁴⁸ more often, only patchy endocardial and interstitial fibrosis with some myofibril hypertrophy are found.^150,153 If biopsy or tests such as radionuclide angiography, Doppler, or echo do not identify either RCM or pericardial disease, exploratory surgery may be needed. Surgery is the most definitive method of differentiating RCM from CP, but the patient with RCM may not tolerate anesthesia and surgery well, so it is used sparingly.¹⁵⁷

There is no specific treatment for RCM. Various regimens have been developed based on the specific cause of RCM¹⁵⁸ (Table 22-6). It is important to rule out the presence of extracardiac diseases that may hamper effective treatment of RCM before it becomes intractable. Diuretics often are administered to reduce pulmonary and venous congestion, but low CO with severe hypoperfusion is a risk. With the characteristic limited stroke volume, heart rate with atrial contraction is important to support CO. Enlarging atria may increase the risk for supraventricular arrhythmias. The lower CO and enlarging atria make chronic anticoagulation important in view of the risk for thrombin formation. A surgical option for RCM is rare with the exception of endomyocardial fibrosis with eosinophilic cardiomyopathy. The fibrotic endocardium may be excised in combination with mitral or tricuspid valve replacement.

TABLE 22-6 Treatment Strategies in Restrictive Cardiomyopathy

CCB, calcium channel blocker.

From Chatterjee K, Alpert J: Constrictive pericarditis and restrictive cardiomyopathy: Similarities and differences. Heart Failure Mont 3:125, 2003.

Survival with RCM depends largely on the causative factor. True idiopathic RCM has a 5-year overall survival rate of 64%, but if increasing signs of pulmonary venous congestion appear, the prognosis worsens.¹⁵⁰ Transplantation is not always an option for adults with RCM because the processes responsible for RCM would invariably affect the newly transplanted heart.

Arrhythmogenic Right Ventricular Cardiomyopathy

Formerly called arrhythmogenic right ventricular dysphasia, arrhythmogenic right ventricular cardiomyopathy (ARVC) was defined by the 1995 WHO as “progressive fibrofatty replacement of right ventricular myocardium, initially with typical regional and later global right ventricular and some left ventricular involvement, with relative sparing of the septum.”⁵⁹ Evidence of a more progressive involvement of not only the RV but LV with long-term follow-up convinced the WHO to classify ARVC as a “disease of the myocardium” that incorporates the many different clinical presentations and aspects of this condition.

ARVC is familial in 30% to 50% of cases, with primarily autosomal dominant inheritance with variable expressivity and reduced penetrance.⁶⁵ The incidence and prevalence are uncertain, but it usually appears during adolescence, though it may occur in younger individuals. It presents most commonly with the onset of arrhythmias ranging from premature ventricular contractions to ventricular fibrillation originating from the RV. The disease is now known to proceed through three phases: (1) concealed phase without symptoms but some EP changes that place patients at risk for sudden death; (2) overt arrhythmias; and (3) advanced stage with myocardial loss, biventricular involvement with CHF.¹⁶⁰ Diagnosis is rare in the early stages,¹⁶¹ but not at autopsy.¹⁶² Distinguishing symptoms may be missing when the structural and functional changes are present or absent in the RV.¹⁶³ Standard diagnostic criteria have continued to be revised.¹⁶⁴ Postmortem examination reveals diffuse or segmental loss of myocardium, primarily in the RV, replaced with fat and fibrous tissue, and right ventricular dilation and thinning of the wall (Figure 22-25). The diagnosis also includes the functional changes associated with the RV beyond the structural alterations. These changes are believed to occur by three possible mechanisms: myoblasts differentiate to adipoblasts, apoptosis, or inflammation.¹⁶¹ An inflammatory process is evident within the myocardial tissue. The replacement of myocardium with fat and fibrous tissue creates an excellent environment for a fatal arrhythmia, possibly the first sign of ARVC.¹⁶⁰ Although considered a disease of the RV, left ventricular involvement also can occur and even precede RV presentation.¹⁶⁵ Sudden death occurs in up to 75% of patients, although it is difficult to accurately state in view of number of patients who go undiagnosed. Sudden death occurs most often during sports-related exercise, primarily from ventricular tachycardia/fibrillation.¹⁶⁶ Although a rare disease, it accounts for 20% of sudden deaths in the young.¹⁶³

Figure 22-25 A, Gross view of the RV outflow tract showing severe transmural loss of the RV freewall and infundibular parchment-like aneurysm. B, Histologic view at high magnification of surviving degenerated RV myocytes in the setting of extensive fatty replacement and tiny interstitial fibrosis. C, Gross and (D) histologic sections of the anterior left ventricular wall showing striking subepicardial fatty infiltration and fibrosis.

(From Corrado D, Basso C, Thiene G, et al: Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: A multicenter study. J Am Coll Cardiol 30;1517, 1997, by permission.)

The electrical instability characteristic of ARVC is not solely responsible for the natural history of the disease. Clinical presentation may range from asymptomatic myopathic involvement to overt clinical disease with diffuse biventricular involvement.^160,166 Progressive right and left ventricular dysfunction can be appreciated with serial echo examinations. Echo findings from 29 patients with ARVC have been described (Figure 22-26).¹⁶⁷ The systolic and diastolic right ventricular outflow tract dimensions were increased on 2D echo. Regional wall motion abnormalities of the RV were common, and more than half of patients had abnormal right ventricular systolic function. Right ventricular trabeculations were also commonly found. Although there are typical echo features in ARVC, the disease may present before the appearance of these morphologic features. Recently, it has been shown that significant ventricular mechanical dyssynchrony is present in 50% of patients.¹⁶⁸ This leads to a more dilated RV, as well as one with poorer function compared with those without it. Myocardial loss with progressive ventricular dysfunction progresses ultimately to CHF, accounting for 20% of deaths. End-stage ARVC may be difficult to distinguish from DCM because the extent of left ventricular involvement only recently has been appreciated.

Figure 22-26 Echocardiographic views from probands meeting Task Force Criteria for arrhythmogenic right ventricular (RV) dysplasia.

A, Right ventricular outflow tract (RVOT) enlargement for the parasternal long-axis view. B, RVOT enlargement from the parasternal short-axis view. C, apical four-chamber view showing a focal RV apical aneurysm (arrow). D, apical four-chamber view showing excessive trabeculations (arrows). E, apical four-chamber view showing a hyper-reflective moderator band (arrow). AoV, aortic valve; LA, left atrium; LV, left ventricle; RA, right atrium.

(From Yoerger DM, Marcus F, Sherrill D, et al: Echocardiographic findings in patients meeting task force criteria for arrhenogenic right ventricular dysplasia. J Am Coll Cardiol 45:860–865, 2005, by permission.).

Diagnosis is based on ECG, structure, genetic studies, and arrhythmias.¹⁶¹ The characteristic ECG includes inverted T waves in the right precordial leads, QRS prolongation > 110 milliseconds, and extrasystoles with left bundle branch block. Diagnosis may depend on endomyocardial biopsy to reveal the distinctive changes of ARVC, yet is unrewarding if the biopsy is obtained from the septal area of the myocardium known for its lack of characteristic features.⁶³ A new immunohistochemical analysis of a biopsy sample has proved to be highly sensitive and specific for the identification of ARVC.¹⁶⁹ The importance of this test is that it has been used to differentiate those patients in the early stages of the disease from the more advanced state. A prospective longitudinal study examined 108 newly diagnosed patients over a 2-year period and found that their clinical profile differed from the patient with the more advanced disease. This finding may offer some options for future treatments.¹⁶³

Anesthesia

Anesthesia management for PFO closure percutaneously requires only conscious sedation in most patients. Anesthesia management for closure of an incidental PFO requires little deviation from the original anesthetic management of the scheduled original cardiac operation. However, once the PFO has been identified, there are some considerations specifically for a PFO.

Routine care for preventing venous air should be standard for cardiac surgery. Obviously, there is a great need to be diligent with the injection of medications to remove extraneous air from entering the venous system. It is important to appreciate the potential for paradoxic embolus with any patient who requires mechanical ventilation. In situations in which the pulmonary vascular resistance may increase, such as during hypercapnia or with positive end-expiratory pressure greater than 15 mm Hg, the potential for right-to-left shunting is increased.²¹¹ Choice of anesthetic seems to have little impact on management of PFO because the patients will tolerate most regimens.

Acute Pericarditis

Acute pericarditis is common, but the actual incidence is unknown because it often goes unrecognized. It generally is self-limited, lasting 6 weeks. Acute pericarditis has many causes (Box 22-4); the most common is viral (30% to 50%).²³⁵ Only 25% of cases have a defined cause, although this is improving.²³⁶ Unfortunately, acute pericarditis resembles many other conditions. Anesthesiologists encounter patients with acute pericarditis in situations of malignancy, MI, postcardiotomy syndrome, uremia, or infection when surgery is required because symptoms are incapacitating and medical therapy has failed.

Acute pericarditis is characterized by fibrin deposits localized on the pericardial surface. A serous effusion may accompany the fibrinous inflammation. Consequently, the mesothelial cell layer is replaced by a fibrin membrane that has white blood cells scattered throughout it. Pericardial fluid may suggest a bacterial, neoplastic, or viral and inflammatory cause.²³⁵ Pericarditis occurs in about 20% of patients who suffer an MI, primarily within the first week.²³⁷ A distinction is made between pericarditis that occurs during the first week and Dressler syndrome, which usually appears 2 to 3 months after an MI. With acute pericarditis, pleuritic chest pain is described in the center of the chest radiating to the back and left trapezius muscle. This pain is more continuous than the intermittent pain of myocardial ischemia. Some degree of dyspnea may be present with acute pericarditis. Occasionally, pericarditis may present as right-heart failure because large and rapid accumulations of pericardial fluid will increase intrapericardial pressure sufficiently to obstruct right ventricular filling through the superior and inferior vena cava, resulting in tamponade. Atrial arrhythmias also may occur.

In general, acute pericarditis can be differentiated from MI by measurement of serum cardiac enzymes, but myocardial enzymes are sometimes found in the serum of patients with pericarditis. It also is common to see the early onset of a low-grade fever that lasts for days to weeks and the presence of a friction rub after the onset of chest pain. Pericardial friction rub is pathognomonic of pericarditis but may be heard only intermittently. Early ECG changes typical of pericarditis are ST-segment elevation in 2 or 3 standard limb leads and in most of the precordial leads. ST-T wave elevation often is present but may be confused with MI (Figure 22-36). Acute pericarditis generally results in diffuse ST-T changes, whereas MI usually is associated with more localized ST-T changes. T-wave inversions follow the acute ST-segment abnormalities as pericarditis enters the subacute phase. Q waves usually do not appear during progression of ECG changes. The echo findings in a patient with suspected acute pericarditis are variable. There may be a pericardial effusion present, the pericardium may be thickened, or it may appear completely normal. If an effusion is present, tamponade physiology must be excluded. If the pericardium appears thickened, additional evidence for constrictive physiology should be sought (see later). The chest roentgenogram may reveal a slightly enlarged cardiac silhouette with a pericardial effusion that indicates the effusion is at least 250 mL. A rapid accumulation of pericardial fluid may cause tamponade. Conversely, if it accumulates slowly, a liter or more of pericardial fluid may collect without symptoms of cardiac tamponade. Pericardial fluid also may be found with CHF, valvular disease, or endocarditis. Pericardiocentesis is performed in acute pericarditis, either to confirm the diagnosis or to relieve tamponade. It may be associated with serious complications, even cardiovascular collapse and shock. Echo should evaluate ventricular contractile function before pericardiocentesis. If repeated aspirations are required for relief of tamponade, pericardiectomy may be necessary.

Figure 22-36 Acute pericarditis: Note the upward-concavity ST elevations in limb leads I, II, aVF, and aVL, and in precordial leads V_3, V_4, V₅, and V₆(light arrows) and the PR-segment elevation in aVR (bold arrow). Acute myocardial infarction: Note the concavity-downward ST elevation in leads I, aVL, V_1, V_2, V_3, V_4, V_5, and V₆(light arrows), indicating a large anterior myocardial infarction.

(Aikat S, Ghaffari S: A review of pericardial diseases: Clinical, ECG and hemodynamic features and management. Cleve Clin J Med 67: 907, 2000, by permission.)

Detection of myocardially directed serum antibodies in Dressler syndrome and in postpericardiotomy syndrome suggests that these syndromes are immune-related responses. Postpericardiotomy syndrome consists of acute nonspecific pericarditis that usually begins between 10 days and 3 months after cardiac surgery or trauma. In a prospective study of 944 adult patients who underwent cardiac surgery, the incidence rate of postpericardiotomy syndrome was 17.8%, although it has been reported as high as 50% of postoperative cardiac patients.²³⁸

Treatment of acute pericarditis consists of symptomatic relief and treating the underlying systemic illness. Symptomatic relief involves support, bed rest, and nonsteroidal anti-inflammatory agents for analgesia. Left stellate ganglion block has been used to relieve unremitting pain.

Constrictive Pericarditis

CP is a dense fusion of the parietal and visceral pericardium that limits diastolic filling of the heart irrespective of cause. The changes in the pericardium can be caused by scarring, induced by a single episode of acute pericarditis or by a prolonged exposure to a recurrent or chronic inflammatory process. CP is a progressive disease. Tuberculosis was a major cause of CP, but currently most cases (33%) are idiopathic.²³⁹ The leading identifiable causes of CP are pericarditis, cardiac surgery, and mediastinal irradiation in the developed world.²⁴⁰Table 22-8 lists some of the causes of chronic CP. Idiopathic, neoplastic, postirradiation, or uremic pericarditis account for most cases of CP that require surgery. Eighteen percent of pericardiectomies are attributed to previous cardiac surgery,²³⁹ which may explain the increase in the number of cases of CP since the middle 1990s.²⁴¹

TABLE 22-8 Causes of Constrictive Pericarditis

CABG, coronary artery bypass grafting.

From Kabbani SS, LeWinter MM: Diastolic heart failure, constrictive, restrictive and pericardial. Cardiol Clin 18:505, 2000.

CP clinically resembles the congestive states of myocardial and chronic liver disease.²³⁴ The most frequent physical signs are jugular venous distention, hepatomegaly, and ascites suggestive of heart failure. Symptoms are nonspecific and progress over years unless the cause is radiation, cardiac surgery, or trauma that can instead develop over months. The normal filling phases of the jugular venous pulse are shown in Figure 22-37. Venous pressure waves in pericardial constriction are characterized by a prominent y descent. Kussmaul’s sign (a paradoxical increase in venous pressure with inspiration) may be present. Systemic venous congestion accounts for some of the classic symptoms of CP such as hepatic congestion and peripheral edema.¹⁵¹ A significant paradoxical pulse occurs in only one third of patients with chronic CP.

Figure 22-37 Schematic depiction of normal jugular venous pressure waves in relation to the electrocardiogram (ECG).

The A wave is a result of atrial contraction; the prominent negative x descent occurs during ventricular systole and is a result of downward displacement of the base of the heart and tricuspid valve, as well as continued atrial relaxation. The small C wave, which interrupts the x descent, is probably caused by the bulging of the tricuspid valve into the right atrium. The V wave represents right atrial filling while the tricuspid valve is closed. Finally, the y descent occurs after opening of the tricuspid valve and during rapid inflow of blood from the right atrium into the ventricle.

(From Legler D: Uncommon diseases and cardiac anesthesia. In Kaplan JA [ed]: Cardiac Anesthesia, 2nd ed. Philadelphia, WB Saunders Company, 1987, p 785, by permission.)

Characteristic ECG changes are P mitrale (broadened P wave), low QRS voltage, and T-wave inversion.²⁴¹ One fourth of patients have atrial fibrillation. Cardiomegaly on chest roentgenogram is nonspecific. Pericardial calcification sometimes is apparent in lateral chest roentgenograms (< 30%),²⁴⁰ although less common than in the past because the incidence of tuberculosis has declined so greatly in developed nations. Although calcification is very specific for CP, it is not very sensitive. CT and MRI may demonstrate the typically thickened pericardium of CP; however, patients with surgically proven CP may have a normal-appearing pericardium with imaging tests in 28% of individuals.¹⁵⁶

A comprehensive echo examination including 2D and Doppler imaging is an essential part of the diagnostic workup and often adequate for diagnosis. The 2D findings may include a thickened pericardium, abnormal motion of the ventricular septum, inferior vena cava dilation, and flattening of the left ventricular posterior wall during diastole.³³ A key diagnostic finding in constriction is ventricular interdependence. Diastolic filling of the ventricles is reliant on each other because the overall cardiac volume is fixed by the stiffened pericardium. With inspiration, intrathoracic pressure declines, as does the pressure in the pulmonary vasculature. The thickened pericardium prevents transmission of this pressure decrease to the ventricles. Thus, filling of the LV decreases just after inspiration because of the decline in pressure within the pulmonary vasculature. Because the interpericardial space is fixed, a decrease in filling pressure to the LV allows increased filling in the RV. The result is a shift in the ventricular septum into the LV during inspiration, as well as an increase in hepatic vein diastolic flow.³³ With expiration, intrathoracic pressure increases, the pressure in the pulmonary vasculature increases, and left ventricular filling is augmented with a shift of the ventricular septum into the RV during diastole. Right ventricular filling is now decreased because of the positive intrathoracic pressure, and flow reversals occur during diastole in the hepatic veins. When several cardiac cycles are viewed consecutively, the ventricular septum appears to “bounce” between the LV and RV.

Ideally, a respiratory variation of 25% or more in mitral inflow E velocity will accompany the diastolic flow reversals in the hepatic veins during expiration and support the diagnosis of pericardial constriction (Figure 22-38). However, this finding is present in only approximately 50% of patients with constriction.^242,243 More recently, tissue Doppler imaging of the mitral annulus has become a valuable tool in the diagnosis of constriction. In myocardial disease, such as RCM, relaxation is impaired and the mitral annular velocity is low (< 7 cm/sec).³³ However, in constriction, relaxation is normal or increased. This can be a valuable tool in differentiating between restrictive and constrictive disease, but there is no uniform acceptance of Doppler indices that differentiate CP from RCM.²³⁴ Right and left cardiac catheterization are necessary to confirm hemodynamic abnormalities in cases that are seen with Doppler imaging.^151,241 Even with the Doppler echo, clinicians must be aware of the loading conditions and respiratory effort of the patient during the Doppler examination. Doppler features in CP have been more extensively reviewed.^151,156,240

Figure 22-38 A, Diagram of a heart with a thickened pericardium to illustrate the respiratory variation in ventricular filling and the corresponding Doppler features of the mitral valve, tricuspid valve, pulmonary vein (PV), and hepatic vein (HV). These changes are related to discordant pressure changes in the vessels in the thorax, such as pulmonary capillary wedge pressure (PCWP) and intrapericardial (IP) and intracardiac pressures. B, Typical mitral inflow and hepatic vein pulsed-wave Doppler recordings in constrictive pericarditis together with simultaneous recording of respiration (bottom) (onset of inspiration at upward deflection and onset of expiration at downward deflection). Left, The first mitral inflow is at the onset of inspiration, and the fourth mitral inflow is soon after the onset of expiration. Mitral inflow E velocity is decreased with inspiration (first and sixth beats). Right, With expiration there is a marked diastolic flow reversal (arrow) in the hepatic vein (sixth beat soon after the downward deflection of the respirometer recording). Hatched area under curve indicates reversal of flow; thicker arrows denote greater filling; D, diastolic flow; exp, expiration; Insp, inspiration; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; S, systolic flow.

(From Oh JK, Seward JB, Tajik AJ: The Echo Manual, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2006, by permission.)

TEE is not tremendously helpful in patients presenting for pericardiectomy. When it is utilized, right ventricular function and degree of tricuspid regurgitation can be evaluated before and after the procedure. However, it is important to remember that the diagnosis of constriction relies on the Doppler findings in spontaneously breathing individuals. These findings have never been evaluated in patients undergoing positive-pressure ventilation, and the operating room is not the correct place to confirm or refute a suspected diagnosis of constriction.

The hemodynamic changes of CP are primarily related to the isolation of the cardiac chambers from respiratory effects on thoracic pressure and a fixed end-diastolic ventricular volume.²⁴⁰ The pericardium limits the filling of the LV during inspiration, which leads to increased filling in the RV because the pericardium is so noncompliant. With expiration, the opposite is seen as the LV is overfilled and the RV is limited. Limitation of right ventricular diastolic filling occurs when the cardiac volume approximates the pericardial volume, usually in mid and late diastole characterized by the square-root or dip-and-plateau sign (Figure 22-39). Filling is limited by the noncompliant pericardium. The square-root sign occurs because the constricting pericardium is essentially part of the ventricular wall. When the ventricle contracts, the pericardium is deformed like a spring. As diastole begins, the spring is released and the ventricle fills rapidly, decreasing the ventricular pressure and creating the dip of the dip-and-plateau wave. As cardiac filling approaches the limit set by the fixed pericardium, the plateau of the ventricular filling curve arrives. There are marked increases of right atrial and left atrial and ventricular filling pressures. Pulmonary artery diastolic pressure, pulmonary capillary wedge pressure, and right atrial pressure are equal and elevated (“pressure plateau”) in CP because of the limitation of the pericardium. Pulmonary artery systolic and right ventricular systolic pressures range from 35 to 45 mm Hg, although PAH is rare. Most importantly, the myocardium is unaffected in CP. The systolic and early diastolic functions are normal. Differences between CP and RCM have been reviewed previously.

Figure 22-39 Right ventricular (RV) and right atrial (RA) pressure tracings recorded with a fluid-filled system from a patient with chronic constrictive pericarditis.

(From Shabetai R: Pathophysiology and differential diagnosis of restrictive cardiomyopathy. Cardiovasc Clin 19:123, 1988, by permission.)

Pericardiectomy is performed for recurrent pericardial effusion and CP. Pericardial dissection for effusive pericarditis is straightforward; however, pericardiectomy for CP is a surgical challenge with an operative mortality rate of 5.9% to 11.9%.²⁴⁴ The 5-year survival rate is 78%.^157,245 The occurrence of tricuspid regurgitation may present similar to CP with signs of right-heart failure and volume overload. In fact, a recent review found one fifth of patients presenting to surgery for CP with significant tricuspid regurgitation.²⁴⁴ Unfortunately, surgical treatment of tricuspid regurgitation with CP had no effect on long-term survival, but also did not increase the risk for surgery. The presence of tricuspid regurgitation may identify a subset of patients with CP who have more advanced disease and may need special attention during anesthetic management.

Persistent low CO immediately after pericardiectomy is the primary cause of morbidity and mortality, occurring in 14% to 28% of patients in the immediate postoperative period.²⁴⁶ The pathophysiologic mechanism of early death after pericardiectomy remains unsolved. Examination of patients who had pericardiectomy for CP with preoperative cardiac catheterization utilizing a micromanometer catheter was performed recently.²⁴⁶ The specialized catheter allowed nonejection indices of cardiac function to be obtained. The study compared patients with abnormalities with those with normal nonejection measurements. The most important finding was that a significant number of patients with CP had abnormal left ventricular contractility and relaxation abnormalities based on a high-fidelity manometer. More importantly, they incurred the greatest risk for operative and long-term mortality. This finding is in contrast with the accepted notion that the pericardium is the problem in these patients and the LV should be normal. Myocardial function is important as a determinant of outcome and even inotropic support. This is consistent with the clinical behavior of patients after pericardiectomy. Although patients with cardiac tamponade usually improve clinically once the pericardium is opened, improvement is not always apparent immediately after pericardiectomy. Instead, noticeable improvement in cardiac function may take weeks, but 90% of patients ultimately experience relief of symptoms with surgery.²³⁹

Median sternotomy provides excellent exposure and access for pericardiectomy, but thoracotomy in the left anterolateral position also is an option. Opinions vary regarding the extent of pericardial resection for alleviation of cardiac constriction and the need for CPB. Recently, total pericardiectomy was found to result in superior outcomes compared with partial pericardiectomy in a retrospective review.²⁴⁷ Removal of adherent and scarred pericardium to release both the RV and LV involves extensive manipulation of the heart and hemodynamic instability. The decision to use CPB is influenced by the surgeon’s confidence in being able to achieve complete pericardial excision with hemodynamic stability. More aggressive approaches to pericardiectomy with CPB have increased over the years as survival has improved, and the trend may continue.²⁴⁴ However, good results have been reported with and without CPB.²⁴⁷ The use of CPB entails full heparinization and may exacerbate blood loss from the many exposed cardiac surfaces. Furthermore, prolonged CPB in debilitated patients contributes to early mortality associated with pericardiectomy. An especially high-risk group of patients undergoing pericardiectomy are those with postradiation CP. They suffer not only from the effects of radiation on the myocardium that may create a more sustained restrictive effect even after pericardiectomy, but also from radiation injury to the lungs.²⁴⁴

Cardiac Tamponade

Cardiac tamponade occurs in a variety of clinical situations, but most often in malignancies with medical patients and after pericardiocentesis.²⁴⁸ It is a continuum of physiologic changes that necessitate rapid diagnosis and treatment. It may be easily missed in the early stages as the signs and symptoms are subtle until it is critical. Decompensated cardiac tamponade is an emergency that requires either immediate pericardiocentesis or surgery to maintain viability.

Tamponade exists when fluid accumulation in the pericardial sac increases to an intrapericardial pressure that limits filling of the heart. The rate of fluid accumulation is the critical factor rather than the absolute volume of fluid that creates the urgency of the condition. The suspicion for cardiac tamponade must exist to increase the chance for a good outcome. Mild tamponade often is asymptomatic. One of the reasons for greater delay in the appreciation of tamponade today than 10 years ago is the tendency of clinicians to overestimate the sensitivity of clinical signs such as hypotension, pulsus paradoxus, and jugular venous distention.²⁴⁹ In several studies, dyspnea is the earliest and most sensitive symptom to indicate tamponade,²⁴⁹ and severe tamponade is accompanied by both dyspnea and chest discomfort.²³⁴ If an ECG is obtained, tamponade may show low-voltage QRS complexes, electrical alternans, and T-wave abnormalities (Figure 22-40).²⁵⁰ Sinus rhythm usually is present in tamponade. The chest roentogram requires at least 200 mL fluid to accumulate in the pericardium before the silhouette, known as the “water-bottle” effect, is seen.²⁵¹ The classic diagnostic triad, known as Beck’s triad, of acute tamponade consists of (1) decreasing arterial pressure; (2) increasing venous pressure; and (3) a small, quiet heart. It is observed in only 10% to 40% of patients.²⁵¹ Pulsus paradoxus may be present (Figure 22-41). It is a decline in systolic blood pressure of more than 12 mm Hg during inspiration caused by a reduced left ventricular stroke volume generated by increased filling of the right heart during inspiration. It is not sensitive or specific for tamponade because it may be present in those with obstructive pulmonary disease, right ventricular infarction, or CP. It may be absent if there is left ventricular dysfunction, positive-pressure breathing, atrial septal defect, or severe aortic regurgitation.

Figure 22-40 Electrical alternans in pericardial tamponade caused by the swinging of the heart within the pericardial space.

(From Aikat S, Ghaffari S: A review of pericardial diseases: Clinical, ECG and hemodynamic features and management. Cleve Clin J Med 67:909, 2000, by permission; originally modified from Longo MJ, Jaffe CC: Images in clinical medicine electrical alternans. N Engl J Med 341:2060, 1999, by permission.)

Figure 22-41 Pulsus paradoxus.

During inspiration, arterial systolic pressure declines by more than 12 mm Hg. EXP, expiration; INSP, inspiration.

(From Reddy PS, Curtiss EI: Cardiac tamponade. Cardiol Clin 8:627–637, 1990, by permission.)

Hemodynamic monitoring may aid in the diagnosis of cardiac tamponade. As diastolic filling begins to disappear, the jugular venous pulse loses a prominent y descent. A prominent x descent remains by the decrease in intrapericardial pressure that occurs during ventricular ejection. Eventually, the pericardial pressure-volume curve becomes almost vertical, so any additional fluid greatly restricts cardiac filling and reduces diastolic compliance.²⁵² Ultimately, the right atrial pressure, pulmonary artery diastolic pressure, and pulmonary capillary wedge pressure equilibrate (Figure 22-42). Equilibration of these pressures (within 5 mm Hg of each other) merits immediate action to rule out acute tamponade. Echo is the current method of choice and most reliable noninvasive method to detect pericardial effusion and exclude tamponade.

Figure 22-42 Hemodynamic changes in cardiac tamponade.

Equilibration of right atrial (RA), pulmonary artery (PA) diastolic, and pulmonary artery wedge (PAW) pressures is demonstrated.

(From Temkin LP, Ewy GA: Cardiac catheterization. In Conahan TJ III [ed]: Cardiac Anesthesia. Menlo Park, CA, 1982, Addison-Wesley, p 1.)

The major hemodynamic changes and compensatory mechanisms of tamponade are outlined in Figure 22-43. Increased intrapericardial pressure on the heart during the cardiac cycle except for ejection is responsible for the hemodynamic changes of cardiac tamponade. Hemodynamic manifestations are due mainly to atrial rather than ventricular compression. Initially, with mild tamponade, increased atrial and pericardial pressures limit diastolic filling. Even though the intracardiac pressures are increased with tamponade, the effective preload is greatly reduced, causing lower stroke volume and CO. Sympathetic reflexes are stimulated to increase heart rate and contractility to maintain CO.²⁴¹ The increasing right atrial pressure also reflexly stimulates tachycardia and peripheral vasoconstriction. Blood pressure is maintained by vasoconstriction, but CO begins to decline, as well as blood pressure, as pericardial fluid continues to increase. Once venous pressures are unable to increase to equal pericardial pressures, the decline in blood pressure is so precipitous that coronary perfusion pressure and blood flow cause ischemia, especially subendocardially.²⁵² This resembles hypovolemic shock and will respond to fluid resuscitation, initially further confusing the diagnosis, but deterioration will soon occur if tamponade is not treated and can become fatal.²³⁴

Figure 22-43 Cardiac tamponade.

Relations among major hemodynamic events and major compensatory mechanisms. Simple arrows represent tamponade sequences; pointed arrowheads represent stimulatory compensatory action; blunt arrowheads represent oppositional compensatory actions.

(From Spokick DH: Pathophysiology of cardiac tamponade. Chest 113:1374, 1998, by permission; originally modified from Spodick DH: In: Spodick DH [ed]: The Pericardium: a Comprehensive Textbook. New York, 1997, Dekker, p 182.)