22 Uncommon Cardiac Diseases
Cardiac tumors
Cardiac tumors increasingly are diagnosed before autopsy because of advancements in imaging, especially metastatic tumors of the heart and pericardium that account for a majority of cardiac tumors. Data pooled from 22 large autopsy series show the prevalence rate of adult primary cardiac tumors is 0.02% but causes considerable morbidity and mortality.1 Primary cardiac tumors in adults are usually benign, with only 20% to 25% malignant.2–5 Diagnosis can be elusive because these tumors may be associated with nonspecific symptoms mimicking other disease entities. Two-dimensional (2D) echocardiography (echo) modalities and magnetic resonance imaging (MRI) have allowed earlier, more frequent, and more complete assessment of cardiac tumors.6,7 The advent of three-dimensional (3D) echo increases the confidence of the diagnosis of a cardiac mass by giving more detailed characterization of mass size, composition, location, and relation to other structures.8
Primary cardiac tumors may originate from any cardiac tissue. Myxoma is the most common cardiac neoplasm, accounting for nearly 50% of tumors in adults (Table 22-1). Less frequently observed benign tumors that may require surgery include rhabdomyoma, fibroma, papillary fibroelastoma, lipoma, and angioma. Malignant primary cardiac tumors include sarcomas that are 95% of these tumors, followed by lymphoma. Sarcomas include angiosarcoma, rhabdomyosarcoma, and acquired immunodeficiency syndrome (AIDS)–related sarcomas.9 Rhabdomyosarcoma represents 20% of malignant neoplasms. Excision of these tumors seldom is curative, in part because of the delay in diagnosis caused by the nonspecific nature of the clinical symptoms. Surgery, radiation therapy, and chemotherapy may slow a tumor’s encroachment on intracavitary spaces or relieve obstruction.
TABLE 22-1 Benign Neoplasms of the Heart
| Neoplasms | Incidence Rate in Adults (%) |
|---|---|
| Myxoma | 45 |
| Lipoma | 20 |
| Papillary fibroelastoma | 15 |
| Angioma | 5 |
| Fibroma | 3 |
| Hemangioma | 5 |
| Rhabdomyoma | 1 |
| Teratoma | < 1 |
From Shapiro LM: Cardiac tumors: Diagnosis and management. Heart 85:218, 2001.
The incidence rate of metastatic cardiac tumors has increased from 0.2% to 10% as a result of improved survival.10 Metastatic cardiac tumors are much more common than primary cardiac tumors. Adenocarcinomas of the lung and breast, lymphomas that are commonly associated with AIDS or transplant immunosuppression, and melanoma are the most frequent metastatic cardiac tumors.11 Melanoma has a special tendency for metastasis to the heart and pericardium. However, metastasis of these tumors rarely is limited to the heart. The onset of arrhythmias or congestive heart failure (CHF) in patients with carcinomas suggests invasion of the myocardium by metastasis, but more than 90% of metastatic lesions to the heart are clinically silent.4
The most effective treatment of primary tumors generally is surgical resection, with 2% operative mortality. This is based on a recent retrospective study of 323 consecutive patients who underwent surgical resection of primary cardiac tumors over a period of 48 years in one institution.12 Recurrence rate in these tumors varied between 3% and 13%, but appeared to be related to a biologic propensity rather than surgical technique, as was previously believed. The overall rate of tumor embolization was 25% compared with previous reports of 12% to 45%. Embolic complications were seen more often in patients with minimal or no symptoms than those with large tumors associated with hemodynamic changes. Papillary fibroelastoma and aortic valve tumors are most commonly preceded by an embolic event. Even patients who are diagnosed by embolic events benefit greatly from surgical resection with excellent short- and long-term survival that is comparable with a cohort of patients with tumors undergoing surgery for other reasons.7 Orthotopic cardiac transplantation has been recommended for unresectable tumors,13 but the benefit is indeterminate. Although more infrequent, the surgical risk and outcome for malignant compared with benign tumor resection are usually much worse,2 especially in younger patients.12
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
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
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.
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
Anesthetic Considerations
Tumor location has a strong influence on anesthetic management. Left atrial myxomas most likely will cause mitral valve obstruction, often in conjunction with PAH and pulmonary venous hypertension. Anesthetic management will closely resemble a patient with mitral stenosis. In contrast, right atrial myxomas may produce signs of right-sided heart failure corresponding to tricuspid valve obstruction. Positioning of the patient for surgery must be carefully performed to detect severe restriction of venous return that may often be followed quickly with profound hypotension and arrhythmias. A large tumor increases the likelihood of hemodynamic instability, whereas a small tumor is associated with increased risk for embolization.7 Perioperative arrhythmias, especially atrial fibrillation or flutter, may arise in 25% of these patients, requiring immediate treatment. Hemodynamic instability with low cardiac output (CO) and arrhythmias are common.
Median sternotomy is recommended for resection of atrial myxoma, although anterior thoracotomy may be used in some benign tumors,2 as well as minimally invasive techniques. Femoral cannulation for initiation of cardiopulmonary bypass (CPB) may minimize the risk for dislodgment or fragmentation of the tumor. Subsequently, a venous cannula can be placed high in the superior vena cava because a biatrial approach to an atrial septal tumor is necessary. The most preferred surgical approach is the single atrial approach.12 Moderate systemic hypothermia, deep topical cooling, and cardioplegic arrest are often used, whereas circulatory arrest is reserved for malignant tumors with significant extension. The heart should not eject during CPB, to minimize systemic embolization of tumor fragments. Electrically induced ventricular fibrillation has been used to prevent ejection of blood after initiation of CPB. Wide excision of the septal base of the myxoma with Dacron or pericardial patching of the resulting defect is the preferred operation.27 Mitral valve replacement may be necessary in large tumors, ventricular side tumors, or tumors with other manifestations besides a propensity to embolize.18 Less extensive operations risk a greater incidence of tumor recurrence because of incomplete tumor excision or a second tumor originating in susceptible atrial tissue. The recurrence rate after complete excision of a sporadic cardiac myxoma is less than 5%.5 After surgery, the most common complication is a 25% incidence rate of transient arrhythmias, mostly supraventricular in nature.
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.
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.)
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.
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
Anesthetic Considerations
Patients who have carcinoid heart disease and require cardiac surgery pose an anesthetic challenge.51–54 A carcinoid crisis with vasoactive mediator release is a life-threatening event that can be provoked by stress, physical stimulation, anesthesia, catecholamines, long-acting opioids (meperidine, morphine), or histamine-releasing muscle relaxants (atracurium). Preoperative control of carcinoid activity is a critical aspect of perioperative management made considerably easier with the administration of octreotide, a synthetic analog of somatostatin that inhibits the vasoactive compounds that produce carcinoid syndrome. It reduces the occurrence of symptoms in more than 70% of patients. The longer half-life of octreotide than somatostatin allows subcutaneous injection of 150 μg three times daily to control symptoms. After surgery, intravenous octreotide (50 to 100 μg/hr) should be started 2 hours before surgery and continued for 48 hours after surgery. Additional intermittent intravenous doses of 50 to 200 μg are given to stop severe hypotension and prevent further carcinoid symptoms.55 Anesthesiologists should be prepared to give large doses of octreotide (300 μg/hr) for stabilization during the intraoperative and postoperative periods. Atrial fibrillation is present in 18% of carcinoid patients, possibly because of the right-sided failure and chamber enlargement, as well as the proarrhythmic effects of seratonin.56 Severe hyperglycemia may occur with octreotide because of its inhibition of insulin secretion, especially in combination with steroids, so glucose monitoring is recommended.50
Preoperative medication to reduce anxiety is strongly suggested for these patients.51 Individuals with more active carcinoid disease experience greater reductions in systolic blood pressure with induction of anesthesia. Etomidate has been recommended for induction instead of thiopental (histamine-releasing) with short-acting opioids (fentanyl and sufentanil) and nonhistamine-releasing muscle relaxants.50 Benzodiazepines are especially valuable for preoperative anxiety, as well as part of anesthetic maintenance. The standard low-to-moderate dose of fentanyl or sufentanil anesthetic with isoflurane is recommended with a nonhistamine-producing muscle relaxant.57
Sudden intraoperative hypotension should be regarded as carcinoid crisis and intravenous octreotide administered until hemodynamic stability returns. Careful attention should be paid to physiologic parameters such as airway pressures as early warning signs of impending carcinoid crisis and treated before onset of severe hypotension. Previously, certain catecholamines (epinephrine, norepinephrine, dopamine, and isoproterenol) were considered to provoke mediator release in carcinoid syndrome, but a recent retrospective study of 100 consecutive patients who underwent cardiac surgery with carcinoid heart disease did not show a significant increase in intraoperative octreotide need or mortality with the use of vasoactive medications.54 The majority of patients in this study received vasopressor agents such as epinephrine, dopamine, and calcium. Because nearly 75% of these patients for cardiac surgery will be in New York Heart Association (NYHA) Class III and require multiple valve replacement, vasoactive medication should be administered according to hemodynamic indices. The safety of vasoactive medications in these patients with octreotide use has been confirmed in a subsequent study.57 Low CO from right ventricular failure and hypotension from vasoplegia are common in the postbypass period, so identifying carcinoid crisis in such circumstances is problematic.
The use of an antifibrinolytic is routine in many centers to reduce blood loss and transfusion requirements associated with CPB and cardiac surgery.58 Because patients with carcinoid heart disease often require surgery involving multiple valves in association with liver metastasis, coagulopathy and excessive hemorrhage after CPB are likely and considered one of the two major complications associated with surgery.55,57 Weingarten et al54 reported significant reductions in red blood cell (RBC) and non-RBC transfusions in patients undergoing cardiac surgery for carcinoid heart disease who received aprotinin compared with those who did not. Aprotinin use was not associated with a reduction in mortality. Aprotinin has the dual properties of antifibrinolysis and anti-inflammation compared with other popular synthetic antifibrinolytic agents (tranexamic acid and aminocaproic acid), but it is no longer available for administration. Synthetic antifibrinolytics appear safe for use in carcinoid heart disease.57
Cardiomyopathy
Previously, the World Health Organization (WHO)/International Society of Cardiology defined cardiomyopathy as heart muscle disease of unknown cause, unlike heart muscle disease attributed to a specific cause or associated with a disease process. With more knowledge concerning pathogenesis and causative factors, the difference between cardiomyopathy and specific heart disease has become less distinct. Previously, cardiomyopathy was classified as dilated, hypertrophic, and restrictive. Over time, each classification has become a recognized clinical condition. In 1995, the WHO/International Society of Cardiology redefined the cardiomyopathies according to dominant pathophysiology or, if possible, by “etiologic/pathogenetic factors.”59 Cardiomyopathies are now defined as “diseases of the myocardium associated with cardiac dysfunction.” The original cardiomyopathies classified as dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), and hypertrophic cardiomyopathy (HCM) were preserved, and arrhythmogenic right ventricular cardiomyopathy (ARVC) was added.
The annual incidence of cardiomyopathy in adults is 8.7 cases per 100,000 person-years.60 Underlying causes of cardiomyopathies are different but carry some prognostic significance.61 General characteristics of all four cardiomyopathies are displayed in Table 22-2. Reviews of the clinical, pathophysiologic, and therapeutic aspects of these cardiomyopathies are available.62–64 This section focuses on cardiomyopathy in relation to cardiac surgery, but it is relevant for the larger number of patients with a cardiomyopathy who undergo noncardiac surgery.
All the cardiomyopathies maintain some relation to genetic transmission. The genetics of these cardiomyopathies will not be addressed in detail, but this does not reflect a lack of importance. Genetic testing is advancing rapidly, with the ability to identify disease-causing mutations in those family members at risk but asymptomatic. The result is heightened clinical surveillance and, possibly, earlier intervention and prevention of the sequelae of the disease. More information is available in this review.65
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
| Diagnosis | No. of Patients (%) |
|---|---|
| Idiopathic dilated cardiomyopathy | 616 (50) |
| Myocarditis | 111 (9) |
| Ischemic cardiomyopathy | 91 (7) |
| Infiltrative disease | 59 (5) |
| Peripartum cardiomyopathy | 51 (4) |
| Hypertension | 49 (4) |
| Human immunodeficiency virus infection | 45 (4) |
| Connective tissue disease | 39 (3) |
| Substance abuse | 37 (3) |
| Doxorubicin related | 15 (1) |
| Other causes | 111 (10) |
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.
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
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.
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.
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
Anesthetic Considerations
Individuals with DCM are extremely sensitive to cardiodepressant anesthetic drugs. Intravenously administered anesthetic agents such as fentanyl (30 μg/kg) provide excellent anesthesia and hemodynamics in patients with ejection fractions less than 30%93 but contribute to prolonged respiratory depression delaying extubation. Shorter-acting narcotics such as remifentanil may be unsuitable for patients with poor left ventricular function undergoing cardiac surgery because of high incidences of bradycardia and severe hypotension.94 A comparison of remifentanil-sevoflurane with fentanyl-etomidate-isoflurane found significantly greater reduction in mean arterial pressure and greater incidence of bradycardia with the remifentanil anesthetic.95 Also, etomidate has been shown to have little effect on the contractility of the cardiac muscle in patients undergoing cardiac transplantation.96 Ketamine has been recommended for induction in critically ill patients97,98 because of its cardiovascular actions attributed mainly to a sympathomimetic effect from the central nervous system. Ketamine is a positive inotrope in the isolated rat papillary muscle and, more importantly, in a model of cardiomyopathic hamsters, did not display a negative inotropic effect.99 This makes ketamine (less than 0.5 mg/kg) an excellent choice to use in combination with fentanyl for induction in patients with severe myocardial dysfunction secondary to cardiomyopathy. The use of propofol with cardiomyopathy may be a concern because cardiovascular depression has been observed possibly because of inhibition of sympathetic activity and a vasodilatory property. However, in a cardiomyopathic hamster model, there was no direct effect on myocardial contractility with propofol.100 Caution is still prudent with propofol because of the indirect inhibitory effects of sympathetic activity that many patients with cardiomyopathy and reduced left ventricular function may depend on for hemodynamic stability.
Volatile agents have long been a concern in persons with failing hearts because of their known depressant effects on myocardial contractility. The effect of currently used volatile anesthetics on intrinsic myocardial contractility is difficult to project clinically. Animal data indicate halogenated volatile agents may have more profound negative inotropic effects in cardiomyopathic muscle than healthy cardiac muscle.101 An anesthetic technique that minimizes myocardial depression is essential. There is little from a cardiovascular standpoint to support a selection of sevoflurane over isoflurane in adults. Although the failing myocardium has been thought to be more sensitive to the depressant effects of volatile agents, there is no synergistic myocardial depression in the presence of moderate left ventricular dysfunction and volatile agents.102 Desflurane, which possesses the lowest blood/gas partition coefficient of the volatile agents allowing rapid induction and emergence, would appear to have some theoretic benefit for early extubation in patients undergoing cardiac surgery. In healthy hamster papillary muscles, desflurane did not appear to have a negative inotropic effect; however, in cardiomyopathic papillary muscles, there was a profound negative inotropic effect.103 On the other hand, sevoflurane and desflurane were shown not to adversely affect the ability of the LV to respond to increased work despite their negative inotropic properties in patients undergoing CPB and cardiac surgery.104 Even with the limitations of generalizing findings of in vitro experiments to clinical situations, this difference of inotropic effect regarding healthy versus cardiomyopathic myocardium is an important distinction not present in all halogenated anesthetics and should be considered in patients with cardiomyopathy.
Invasive hemodynamic monitoring is indispensable with volatile agents and DCM. Of particular pertinence for anesthesiologists is that physical signs and symptoms of DCM may not accurately reflect physiologic parameters. Eighty percent of patients with pulmonary capillary wedge pressures greater than 25 mm Hg have no detectable rales.105 The use of more aggressive monitoring will depend partially on the operation. Patients receiving implantable defibrillators usually have severely depressed left ventricular function but are routinely managed without a PAC. Echo also is useful for patients undergoing both cardiac and noncardiac surgery. For most cardiac surgical procedures (mitral valve surgery, left ventricular assist devices), echo is considered necessary to evaluate the results of the operation. In both cardiac and noncardiac surgery, echo can provide real-time data as to how interventions such as addition of inotropes or vasodilators change ventricular function and indirectly assess CO.
Hemodynamic instability that may occur with DCM can be lessened with a low dose of inotrope and vasodilator. Acute administration of inotropes, such as dobutamine, improves hemodynamics temporarily, but tolerance begins in 3 to 4 days.77 Phosphodiesterase-3 inhibitors are useful if combined with another β-adrenergic agonist, such as milrinone and epinephrine, for short-term hemodynamic support. Afterload reduction in DCM is important because it improves regional and global indices of ventricular relaxation and ejection fraction during anesthesia when myocardial depression may be significant. It also may reduce valvular regurgitation and atrial volumes.106 The use of levosimendan, an effective calcium-sensitizing agent with vasodilatory and inotropic features, may be an excellent agent to maintain hemodynamics because it also increases myocardial performance without major changes in the oxygen consumption or effects on the diastolic function.107 Some patients with DCM may be chronically taking amiodarone, which has a negative inotropic effect that interacts with volatile agents to further reduce contractility and conduction, requiring careful titration of these anesthetic agents.108 Arrhythmogenic factors such as hypokalemia, hypomagnesemia, and sympathetic activation should be monitored and corrected. Because of the structural nature of DCM, atrial fibrillation is likely to be present in 25% of cases. Patients with atrial fibrillation and DCM show significantly diminished myocardial perfusion and perfusion reserve compared with those in normal sinus rhythm.109
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.
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
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