Myxoma

Often a diagnostic challenge, myxoma, a benign, solitary neoplasm that is slowly and microscopically proliferating, 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. The undifferentiated cells of a myxoma develop along a variety of cell lines, accounting for the multiple presentations and pathologic conditions observed. Any age group can be affected. Myxomas predominate in the 30- to 60-year-old age range, with more than 75% of the affected patients being women.

Rarely discovered by incidental echocardiography examination, myxomas may manifest a variety of symptoms. The classic triad includes embolism, intracardiac obstruction, and constitutional symptoms. Approximately 80% of individuals present with one component of the triad, yet up to 10% may be asymptomatic even with mitral myxomas, arising from both atrial and ventricular sides of the anterior mitral leaflet. The most common initial symptom, dyspnea on exertion, reflects mitral valve obstruction usually present with LA myxomas (Fig. 18-1). 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 may also occur. The persistence of sinus rhythm in the presence of such symptoms may help distinguish atrial myxoma from mitral stenosis. Severe pulmonary hypertension without significant mitral valve involvement suggests obstruction of the tricuspid valve and recurrent pulmonary emboli known to occur with a myxoma in the RA or right ventricle (RV). Before echocardiography, angiography was used to identify all myxomas, but now it is only useful to confirm the diagnosis or determine coronary anatomy if considered necessary. TEE is 100% sensitive for diagnosis of myxoma. Specifically, it yields morphologic detail in the evaluation of cardiac tumors, including points of tumor attachment and degree of mobility. Computed tomography (CT) and MRI can help delineate the extent of the tumor and its relationships to surrounding cardiac and thoracic structures. MRI is especially valuable in the diagnosis of myxoma when masses are equivocal or suboptimal on echocardiography or if the tumor is atypical in presentation. Difficulty may arise in differentiating thrombus from myxoma because both are so heterogeneous.²

Figure 18-1 Transesophageal echocardiogram showing a left atrial myxoma prolapsing across and obstructing the mitral valve.

(Reprinted with permission from Shapiro LM: General cardiology cardiac tumors: Diagnosis and management. Heart 85:219, 2001. Reproduced with permission from the BMJ Publishing Group.)

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, primarily because of the risk of embolization. Generally, the time interval between onset of symptoms and surgical resection is about 4 months, but surgery has been delayed for 10 years. Surgery is associated with a mortality rate of 0% to 3%.

Tumors with Systemic Cardiac Manifestations

Carcinoid tumors are metastasizing tumors that arise primarily from the small bowel, occurring in 1 to 2 per 100,000 people in the population. Fewer than 5% of individuals with carcinoid tumors develop carcinoid syndrome, which is characterized by vasomotor symptoms, bronchospasm, and right-sided heart disease attributed to the 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 that impairs the ability of the liver to inactivate large amounts of vasoactive substances.

Initially described in 1952, carcinoid heart disease develops in more than 50% of patients with carcinoid syndrome and may be the initial feature. The prognosis has improved in the past 20 years for individuals with malignant carcinoid tumors, but carcinoid heart disease still causes considerable morbidity and mortality. Circulating serotonin levels have been found to be more than twice as high in persons with carcinoid syndrome who develop carcinoid heart disease. Carcinoid heart disease characteristically involves tricuspid regurgitation and pulmonic stenosis, resulting in severe right-sided heart failure. The left heart is usually spared involvement in carcinoid heart disease, possibly due to inactivation of serotonin in the lungs, but it may exist with the presence of a bronchial carcinoid or an interatrial shunt.

Without treatment, survival with carcinoid heart disease rarely exceeds 3 years. Surgery to replace both tricuspid and pulmonary valves with either bioprosthetic or mechanical valves is the only viable therapeutic option. The optimal timing to operate is uncertain, but consideration should be given to when signs of RV failure appear, in combination with steady follow-up. Perioperative mortality has been reported as high as 35%, but more recent data suggest it is below 10%. Despite surgery, RV dysfunction persists.

Dilated Cardiomyopathy

DCM is by far the most common of the four cardiomyopathies in adults (60%). It is a condition of diverse etiologies such as viral, inflammatory, toxic, or familial/genetic and is associated with many cardiac and systemic disorders that influence the prognosis.

DCM is characterized morphologically by enlargement of RV and LV cavities without an appropriate increase in the ventricular septal or free wall thickness, giving an almost spherical shape to the heart. The valve leaflets may be normal, yet dilation of the heart may cause a regurgitant lesion secondary to displacement of the papillary muscle.

With DCM, there is more impairment of systolic function even though diastolic function is affected. As contractile function diminishes, stroke volume is initially maintained by augmentation of end-diastolic volume. Despite a severely decreased ejection fraction, stroke volume may be almost normal. Eventually, increased wall stress due to marked LV dilation and normal or thin LV wall thickness, combined with probable 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 of time.

Management of acute decompensated CHF continues to evolve, but the onset of overt CHF is a poor prognostic indicator for patients with DCM. 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.⁴ All patients receive angiotensin-converting enzyme inhibitors (ACEIs) to reduce symptoms, improve exercise tolerance, and reduce cardiovascular mortality without a direct myocardial effect. Perhaps more important than the hemodynamic effects, ACEIs suppress ventricular remodeling and endothelial dysfunction, accounting for the improvement in mortality noted with this medication in DCM. Other afterload-reducing agents, such as selective phosphodiesterase-3 inhibitors like milrinone, may improve quality of life but do not affect mortality, so they are rarely administered in chronic situations. Spironolactone has assumed a greater role in treatment as mortality was reduced by 30% from all causes in patients receiving standard ACEIs for DCM with the addition of spironolactone in a large double-blind randomized trial. The use of β-blockers in DCM has provided not only symptomatic improvement but also substantial reductions in sudden death and progressive death in patients with New York Heart Association (NYHA) class II and III heart failure. This is especially significant because almost 50% of deaths are sudden. High-grade ventricular arrhythmias are common with DCM. Approximately 12% of all patients with DCM die suddenly, but overall prediction of sudden death in an individual with DCM is poor. The best predictor of sudden death remains the degree of LV 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. Antiarrhythmic medications are hazardous in patients with poor ventricular function owing to their negative inotropic and sometimes proarrhythmic properties. Amiodarone is the preferred antiarrhythmic agent in DCM because its negative inotropic effect is less than that of other antiarrhythmic medications and its proarrhythmic potential is lowest. Implantable defibrillators reduce the risk of sudden death as well as reducing mortality. Evidence has indicated that with previous cardiac arrest or sustained ventricular tachycardia, more benefit was gained from use of an implantable defibrillator. This was based on a 27% reduction in the relative risk of death attributed to a 50% reduction in arrhythmia-related mortality compared with treatment with amiodarone.

Patients who are resistant to pharmacologic therapy for CHF may derive benefit from dual-chamber pacing, cardiomyoplasty, or LV assist devices. Placement of LV assist devices has improved patients sufficiently to avoid heart transplantation or enable later transplantation. Transplantation can substantially prolong survival in patients with DCM, with a 5-year survival of 78% in adults.

Hypertrophic Cardiomyopathy

Referred to as idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy, and asymmetric septal hypertrophy, among other names, the accepted term is now hypertrophic cardiomyopathy.⁵ In the past 40 years, advancements regarding the hemodynamics, systolic and diastolic abnormalities, electrophysiology, genetics, and clinical care of HCM have contributed to a greater understanding of this disease. HCM is the most common genetic cardiac disease, with marked heterogeneity in clinical expression, pathophysiology, and prognosis. The overall prevalence for adults in the general population is 0.2%, affecting men and women equally.

HCM is a primary myocardial abnormality with sarcomeric disarray and asymmetric LV hypertrophy. The extent of sarcomeric disarray distinguishes HCM from other conditions. The hypertrophied muscle is composed of muscle cells with bizarre shapes and multiple intercellular connections arranged in a chaotic pattern. Increased connective tissue combined with markedly disorganized and hypertrophied myocytes contributes to the diastolic abnormalities of HCM that manifest as increased chamber stiffness, impaired prolonged relaxation, and an unstable EP substrate that causes complex arrhythmias and sudden death. Diastolic abnormalities are more a function of impaired relaxation than of decreased compliance. Impaired relaxation produces a reduced rate of volume during rapid ventricular filling, with an increase in atrial systolic filling associated with atrial dilation. As the abnormal diastolic properties affect ventricular filling, the clinical manifestations of HCM become evident. In contrast to the diastolic function, systolic function in HCM is usually normal, with an increased ejection fraction that eventually diminishes in the later stages of the disease.

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 is marked in the basal anterior ventricular septum, with a disproportionate increase in the thickness of the ventricular wall relative to the posterior free wall. The LV wall thickness is the most extensive of all cardiac conditions. 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.

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.

Two-dimensional echocardiography establishes the diagnosis of HCM easily and reliably. Classic echocardiography features are thickening of the entire ventricular septum from base to apex disproportional to that of the posterior wall, poor septal motion, and anterior displacement of the mitral valve without LV dilation (Fig. 18-2). Echocardiography has reduced the need for invasive catheterization procedures, unless coronary artery disease (CAD) or severe mitral valve disease is suspected or diagnostic problems are present. MRI has been useful in cases in which echocardiography is technically inadequate.

Figure 18-2 A, Parasternal long-axis view of a patient with hypertrophic cardiomyopathy (HCM). There is increased thickness of the septum from the base to the apex as well as the anterior free wall. The left ventricular cavity size is normal here. B, Transesophageal echocardiography in a patient with HCM for myectomy-myotomy. Early systole, demonstrating septal hypertrophy and narrowing of the left ventricular outflow tract (LVOT). C, Same patient in late systole. Systolic anterior motion of the mitral leaflets produced by a Venturi effect in the LVOT created by the high blood velocity. D, After myectomy-myotomy, the arrowheads point to the area of myocardium removed and the widened LVOT. LA = left atrium; RA = right atrium; LV = left ventricle; RV = right ventricle; VS = ventricular septum; MV = mitral valve; Ao = aorta; PW = posterior wall.

(A, reprinted with permission from Giuliani ER, Fuster V, Gersh BJ, et al: Cardiology: Fundamentals and Practice. St. Louis, Mosby, 1991; B, C, and D courtesy of Martin D. Abel, MD, Mayo Clinic, Rochester, MN.)

Two thirds of individuals with LV outflow tract obstruction become severely symptomatic and 10% die within 4 years of diagnosis. The outflow tract is narrowed from septal hypertrophy and anterior displacement of the papillary muscles and mitral leaflets, creating a dynamic LV outflow obstruction (see Fig. 18-2). 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 systolic anterior motion (SAM), mitral septal contact, and ultimately LV outflow obstruction. SAM of the anterior leaflet may also cause mitral regurgitation. 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 is worsened by decreased end-diastolic volume, increased contractility, or decreased aortic outflow resistance (Fig. 18-3).

Figure 18-3 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; MV = mitral valve; VS = ventricular septum; LV = left ventricle; PW = posterior wall.

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

Surgical correction of HCM is directed primarily at relieving symptoms of LV obstruction in the 5% of patients who are refractory to medication.⁶ In general, these are individuals with subaortic gradients more than 50 mmHg and frequently associated with severe CHF. A myotomy-myectomy through a transaortic approach relieves the obstruction. The muscle is excised from the proximal septum extending just beyond the mitral valve leaflets to widen the LV outflow tract. This is a technically challenging operation due to the limited exposure and precise area to excise the muscle. It is usually reserved for centers with considerable experience. When myectomy is successful, the outflow tract of the LV is widened and SAM, mitral regurgitation, and outflow gradient are all decreased.

Restrictive Cardiomyopathy

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.” 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.

RCM may be classified as myocardial (infiltrative, noninfiltrative, and storage) or endomyocardial (Box 18-1) according to etiology. RCM may be associated with another disease entity except pericardial disease. Restrictive myocardial disorders are characteristically atypical in presentation and hemodynamics at times, complicating perioperative management.