Answer to question 2 Figure 13.12 shows a magnetic resonance angiogram of the thoracic cavity. In this angiogram, rapid blood flow is recorded as lighter shading while slower flow is indicated in darker tones. The heart is anterior in this photo (blurred due to motion artifact), and the descending aorta is located posteriorly. Within the aorta a partition is visualized, which is the intimal “flap” of the dissection. On one side of the flap normal blood flow is present and is the lighter of the two zones. This represents the “true lumen” of the aorta. The “false lumen” is the channel created by the dissection process within the media of the aorta and is the darker of the two zones. This patient subsequently underwent contrast aortography (Figure 13.13). The thoracic angiogram shows the catheter in the “true” aortic lumen. In this study the entire length of the dissection is visualized from its origin just above the aortic valve to its distal aspect within the descending aorta. Also note the opacification of the left ventricle, which indicates aortic regurgitation through an incompetent aortic valve. These studies show this to be a proximal (type A) dissection with involvement of the ascending aorta as well as the arch and descending aorta. Answer to question 3 The ideal study would be one that is readily available, quickly performed, sensitive for the diagnosis of dissection anywhere along the aorta, able to identify the site of intimal disruption (which determines the surgical approach), and can identify concomitant aortic regurgitation or pericardial effusion. Historically the “gold standard” for the diagnosis of aortic dissection has therefore been invasive catheterization and angiography. However, the newer non-invasive modalities are highly sensitive and often eliminate the need for angiography. These include magnetic resonance imaging, transesophageal echocardiography, and computed tomography. Although the positive and negative predictive values favor magnetic resonance imaging over the other non-invasive imaging studies (see Table 13.3), the use of magnetic resonance imaging in this setting may be limited by the long image acquisition time. In addition, for critically ill patients magnetic resonance imaging is not practical because it is impossible to attach intravenous infusion pumps with metallic components or mechanical ventilators to the patient within the magnetic imaging field. The advantage of transesophageal echocardiography is that it is usually readily available; it is portable, accurate, and quick to perform and interpret; and it is less costly than magnetic resonance imaging. It can be used to detect aortic regurgitation and to assess ventricular function. Computed tomography is also sensitive and accurate, but suffers the disadvantages of its lack of portability and the inability to assess aortic regurgitation. Thus there are Cardiology Core Curriculum 436 clear trade-offs with any of these non-invasive techniques; therefore, at each medical center the best diagnostic test for aortic dissection is the one that can be performed most rapidly and with the greatest local expertise. Answer to question 4 Once the diagnosis of a proximal aortic dissection is confirmed, the immediate management strategy is to call for surgical consultation followed by emergent repair. Medical management (antihypertensive and vasodilator therapy, as described below) should not delay surgical intervention. Ideally, surgical evaluation should proceed in parallel with the diagnostic strategy if the initial differential diagnosis includes aortic dissection. For patients with a distal (type B) aortic dissection, the goal is to lower intra-aortic pressure and the force of ventricular contraction (dP/dt) in order to prevent further extension of the dissection. This is initially accomplished by the administration of intravenous β-blockers (typically metoprolol or the short-acting agent esmolol), as well as antihypertensive/vasodilator therapy using agents such as intravenous nitroprusside. Once stabilized, oral β-blockers and other antihypertensive agents can be substituted. Answer to question 5 Proximal (type A) aortic dissections should be repaired surgically to improve survival, whereas distal (type B) aortic dissections are treated medically with control of blood pressure as outlined above. However, there are exceptions to this rule. Type B aortic dissections complicated by compromise of blood flow to vital organs, impending aortic rupture, or retrograde extension into the ascending aorta should prompt surgical repair. In addition, aortic dissections in all patients with Marfan’s syndrome should be surgically repaired because of the high incidence of redissection if treated only with medications. The patient in this case underwent successful surgical repair of the ascending aorta and replacement of the aortic valve, followed by aggressive long-term antihypertensive therapy. Heart tumors Tumors of the heart are uncommon but can cause significant morbidity, often in young individuals. Tumors may be primary, but are more often metastatic from extracardiac sites. Cardiac neoplasms may be asymptomatic. Alternatively, they may result in a constellation of findings due to their ability to act as space occupying lesions and interfere with normal intracardiac blood flow, cause pulmonary or systemic embolism, invade and destroy myocardial Pericardial disease, disease of the aorta, and heart tumors 437 tissue, and cause constitutional symptoms that mimic systemic illnesses. Primary benign tumors of the heart Approximately 75% of the primary tumors of the heart are benign and 25% are malignant. Cardiac myxomas are the most common primary tumors, and are usually pathologically benign and curable in general. Myxomas, such as the one presented in the case history below, appear as large gelatinous, shiny, lobular masses, often several centimeters in diameter (Figure 13.14). Microscopically, they consist of scattered stellate cells in a mucinous matrix. They may arise from the endothelium of any cardiac chamber. However, 75% of myxomas appear in the left atrium, approximately 20% in right atrium, and the remainder in the ventricles or on the surface of the cardiac valves. Atrial myxomas are most often pedunculated and 85% of the time arise from the fossa ovalis in the mid-atrial septum. Myxomas appear as solitary lesions 95% of the time, and in the remainder multiple tumors are present. Up to 10% of myxomas occur in a hereditary manner. The clinical relevance of cardiac myxomas is due to three features of the tumor. First, these are generally large, mobile, space occupying lesions that can obstruct the inflow of blood to or outflow from the cardiac chamber in which they appear. Second, friable tumor Cardiology Core Curriculum 438 Figure 13.14 Gross pathologic specimen of a resected left atrial myxoma. The tumor consists of a stalk with large gelatinous, shiny lobules fragments or superimposed thrombi embolize to the systemic circulation in 30–70% of patients with left atrial myxoma. In a similar manner, pulmonary embolism may result from emboli derived from a right atrial myxoma. Finally, constitutional symptoms such as fever, chills, sweats, fatigue, and myalgias occur and may be related to necrosis of portions of the myxoma or tumor secretory products. Left atrial myxomas may transiently obstruct blood flow across the mitral valve during diastole. Symptoms are intermittent and may relate to changes in body position due to the movement of the tumor within the chamber. In such patients, episodic dyspnea, light- headedness and syncope often occur. The physical examination of a patient with left atrial myxoma may demonstrate the stigmata of peripheral systemic emboli and an abnormal cardiac examination. In early diastole, a low-pitched “tumor plop” may be heard, as the mobile tumor strikes the mitral valve or heart chamber wall. If partial obstruction of transmitral flow ensues, then a diastolic murmur mimicking mitral stenosis can be heard. In some cases, chronic repetitive traumatic injury of the mitral valve by the myxoma may result in leaflet damage and the murmur of mitral regurgitation. Patients with right atrial myxoma may also manifest positional dyspnea and syncope because of intermittent obstruction of the tricuspid valve. In addition, symptoms typical of pulmonary emboli may result if there is dislodgement of tumor fragments. Signs of right sided heart failure may also appear, including jugular venous distension, hepatomegaly, and peripheral edema. A tall “a” wave may be present in the jugular venous pulse if right atrial contraction causes the tumor to partially obstruct blood flow across the tricuspid valve. Laboratory studies in patients with myxomas reveal anemia, leukocytosis, and an elevated erythrocyte sedimentation rate. The chest x ray film usually demonstrates a normal cardiac silhouette; rarely, calcification within a myxoma may be visualized on the plain film. The electrocardiogram may demonstrate left or right atrial enlargement, reflecting obstructed blood flow in the chamber that contains the tumor. The most useful imaging modality is two-dimensional echocardiography because myxomas are usually readily identified using this technique (Figure 13.15). Although less convenient to perform, computed tomography and magnetic resonance imaging have sensitivities of detection similar to that of echocardiography. The curative treatment of an intracardiac myxoma is surgical excision. Rarely, the tumor recurs (most often in the familial forms of myxoma), so that yearly echocardiography is recommended for 5 years following excision of the tumor. Cardiac myxomas have been reported as part of a syndrome including lentigines, blue nevi, and various endocrine abnormalities Pericardial disease, disease of the aorta, and heart tumors 439 (Cushing’s disease, acromegaly, testicular tumors, and myxoid fibroadenomas of the breast). Other benign tumors of the heart are often asymptomatic, but they too may obstruct intracardiac blood flow or result in arrhythmias and/or conduction disturbances. Fibroelastomas are sometimes found as an incidental finding on echocardiography. They arise as small masses on the cardiac valves or adjacent endothelium. They are seldom symptomatic, but occasionally interfere with valvular function. Rhabdomyomas are the most common cardiac tumors in children. They generally occur within the ventricles, are often multiple, and depending on their size and location they may mimic valvular stenosis, restrictive or hypertrophic cardiomyopathy, or result in congestive heart failure. Cardiac lipomas are often an Cardiology Core Curriculum 440 Figure 13.15 Echocardiogram, apical four chamber view, demonstrating a mass (M) extending between the left atrium (LA) and left ventricle (LV). RA, right atrium; RV, right ventricle incidental finding at autopsy. Sometimes they become quite large and obstruct intracardiac flow or cause arrhythmias. Primary malignant tumors of the heart Primary cardiac malignant tumors are usually a form of sarcoma and appear more commonly in the right side of the heart. Symptoms arise from intracavitary growth as well as invasion of the myocardium, conduction system, and pericardium. Depending on the size and rate of progression, malignant cardiac tumors can result in sudden congestive heart failure, syncope, arrhythmias, and conduction disturbances. Myocardial invasion can result in electrocardiographic abnormalities that mimic acute myocardial infarction. Erosion into the pericardium results in large hemorrhagic effusions. In most cases, death occurs within weeks to months following initial presentation of malignant cardiac tumors. Cures are uncommon, even with surgical and radiation therapy. Rarely, cardiac transplantation has been performed successfully. Of the modalities available to image suspected malignant cardiac tumors, magnetic resonance stands out because it provides superb anatomic detail that can delineate the extent of tumor invasion and the relationship to normal cardiac structures. Metastatic tumors to the heart Metastatic tumors to the heart are much more common than primary cardiac tumors. They are found in 10% of patients who die from extracardiac malignancies, but they are rarely symptomatic during life. Cardiac metastases are most commonly found in patients with cancer of the lung, breast, melanoma, leukemia, and lymphoma. Metastases arising from Kaposi’s sarcoma have been found in patients with AIDS. Metastatic cardiac tumors may invade the heart via the blood stream, the lymphatic system, or by direct invasion from the primary neoplastic site. Grossly, they may appear as small nodules or as a diffuse infiltration into the myocardium and/or pericardium. When symptomatic, clinical findings are similar to those of primary cardiac malignant tumors. Most commonly, symptoms are attributable to pericardial metastasis with large malignant hemorrhagic effusions, which often result in cardiac tamponade. Infiltrating tumor can also encase the heart and result in physiology resembling that of constrictive pericarditis. The prognosis of an individual with metastatic cardiac tumor is poor, and therapy is generally palliative. In rare cases, cardiac invasion Pericardial disease, disease of the aorta, and heart tumors 441 may respond to radiation or chemotherapy. Acute deterioration due to cardiac tamponade is treated by pericardiocentesis or, if recurrent, by surgical creation of a pericardial window for continued drainage. Occasionally, certain carcinomas of extracardiac origin may extend into the inferior vena cava and enter the right heart chambers via that route. Such lesions are often readily visualized by echocardiography or other imaging modalities. Examples of such tumors include renal cell and hepatocellular carcinoma. Case studies Case 13.3 A 22-year-old male college student and football player has been in previously good health. Over the months before admission he noted intermittent low grade fever, fatigue, and decreased appetite. Over the 2 weeks before admission he experienced repeated episodes of severe light-headedness and sudden dyspnea with rapid changes in position, such as jumping to catch the football. The coach dismissed him from the football team because of his poor performance. His mother, however, was not satisfied that a cause had been found for his symptoms, and brought him to the hospital for evaluation. His past medical history is unremarkable. He is a non-smoker, non-drinker, and denies use of illicit drugs. Examination. Physical examination: the patient appeared tired. No peripheral stigmata of embolic phenomena. Temperature: 99°F (37·2°C). Weight: 200 lb (90·6 kg). Pulse: 64 beats/min, regular, normal sinus rhythm. Blood pressure: 120/80 mmHg. Jugular venous pulse: 5 cm. Cardiac impulse: normal. First heart sound: normal. Second heart sound: splits normally on inspiration. In the left lateral decubitus position, at the apex, an intermittent early diastolic low frequency sound was heard, which was followed by a brief diastolic murmur. Chest examination: normal air entry, no rales or rhonchi. Abdominal examination: soft abdomen, no tenderness. Normal liver span. No other obvious abnormalities. No peripheral edema. Femoral, popliteal, and foot pulses were equally diminished. Carotid pulses: normal, no bruits. Investigations. Hematocrit: 44%. White blood cell count: 8 300/mm 3 . Erythrocyte sedimentation rate: 34. Electrocardiogram: sinus rhythm with normal intervals and axis; a normal tracing. Echocardiography: 5 cm × 5 cm mobile mass within the left atrium (see Figure 13.15). It appears pedunculated and attached to the mid-portion of the atrial Cardiology Core Curriculum 442 septum. During diastole, the mass prolapses into the mitral valve orifice with partial obstruction of left ventricular inflow. Questions 1. What is the differential diagnosis of the echocardiographic lesion? 2. Is this likely to be a benign or malignant lesion? 3. What complications may arise from this process? 4. What therapy is indicated? Answers Answer to question 1 This young man presents with recent onset of constitutional symptoms, positional light-headedness, and a large mass within the left atrium that appears pedunculated. The differential diagnosis of this lesion includes a large thrombus, an intracardiac tumor or possibly infective endocarditis. Any of these conditions may present with the described constitutional symptoms. There is no apparent clinical reason for this individual to have an intracardiac thrombus. Notably, the left atrium is not significantly enlarged, and he does not have mitral valve disease or atrial fibrillation. The pedunculated mass appears to be attached to the interatrial septum, which is the most typical position for a left atrial myxoma. Conversely, thrombus within the left atrium is most commonly observed in the region of the atrial appendage. Blood cultures had been obtained but were negative, ruling against endocarditis. Answer to question 2 Of the heart tumors, the location, pedunculated attachment, and origin at the mid-intra-atrial septum in this case are most consistent with a cardiac myxoma, as described below. Myxomas are usually pathologically benign and are surgically curable. Answer to question 3 The clinical presentation of left atrial myxoma includes constitutional symptoms (fever, chills, sweats, fatigue, myalgias), systemic emboli including stroke, and obstruction in intracardiac blood flow. In this young man’s case, sudden changes in position resulted in syncope due to obstruction of diastolic blood flow across the mitral valve into the left ventricle. Answer to question 4 The presence of a left atrial myxoma with evidence of obstructed blood flow or embolization is a medical emergency, and prompt surgical excision should follow. Pericardial disease, disease of the aorta, and heart tumors 443 Further reading Diseases of the pericardium Cameron J, Oesterle SN, Baldwin JC, Hancock EW. The etiology spectrum of constrictive pericarditis. Am Heart J 1987;113:354–60. Fowler NO. The pericardium in health and disease. New York: Futura Publishing Co, 1985. Klein AL, Cohen GI. Doppler echocardiographic assessment of constrictive pericarditis, cardiac amyloidosis, and cardiac tamponade. Cleve Clin J Med 1992;59:278–90. Lilly LS, ed. Pathophysiology of heart disease. Philadelphia: Lea & Febiger, 2002. Oh JK, Hatle LK, Seward JB, et al. Diagnostic role of Doppler echocardiography in constrictive pericarditis. J Am Coll Cardiol 1994;23:154–62. Shabetai R, ed. Diseases of the pericardium. Cardiol Clin 1990;8:579–716. Singh S, Wann LS, Schuchard GH, et al. Right ventricular and right atrial collapse in patients with cardiac tamponade: a combined echocardiographic and hemodynamic study. Circulation 1984;70 :966. Soulen RL, Stark DD, Higgins CB. Magnetic resonance imaging of constrictive pericardial disease. Am J Cardiol 1985;55:480. Spodick DH. Macrophysiology, microphysiology, and anatomy of the pericardium: a synopsis. Am Heart J 1992;124:1046–51. Diseases of the aorta Belkin M, Donaldson MC, Whittemore AD. Abdominal aortic aneurysms. Curr Opin Cardiol 1994;9:581–90. Cigarroa JE, Isselbacher EM, DeSanctis RW, Eagle KA. Diagnostic imaging in the evaluation of suspected aortic dissection: old standards and new directions. N Engl J Med 1993;328:35–43. Ernst CB. Abdominal aortic aneurysm. N Engl J Med 1993;328:1167–72. Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD). JAMA 2000;283:897–903. Izzo JL, Black HR, ed. Hypertension primer: the essentials of high blood pressure. Dallas: American Heart Association, 1993. Kouchokos NT, Daigenis D. Surgery of the thoracic aorta. N Engl J Med 1997;336:1876–87. Nienaber CA, von Kodolitsch Y, Nicolas V, et al. Definitive diagnosis of thoracic aortic dissection: the emerging role of noninvasive imaging modalities. N Engl J Med 1993;328:1–9. Heart tumors Reynen K. Cardiac myxomas. N Engl J Med 1995;333:1610–17. 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 1985;5:1465–73. Reeder, GS, Khandheria BK, Seward JB, et al. Transesophageal echocardiography and cardiac masses. Mayo Clin Proc 1991;66:1101–9. Salcedo EE, Cohen GI, White, RD, Davison MB. Cardiac tumors: diagnosis and management. Curr Probl Cardiol 1992;17:73–137. Cardiology Core Curriculum 444 445 14: Pulmonary embolism and pulmonary hypertension SAMUEL Z GOLDHABER Pulmonary embolism and deep venous thrombosis (DVT) result in hundreds of thousands of hospitalizations, and attempts at prompt diagnosis and appropriate treatment of this illness cost billions of dollars annually. The incidence of pulmonary embolism and DVT increases steadily with age. For patients with pulmonary embolism, the most dangerous period precedes ascertainment of the correct diagnosis. The latter is quite difficult despite the availability of traditional tests such as lung scanning, right heart catheterization, and pulmonary angiography, as well as plasma D-dimer enzyme linked immunosorbent assay (a blood screening test), leg ultrasonography with color Doppler imaging (to detect venous thrombosis), chest computed tomography scanning, and echocardiography. Contemporary diagnosis of pulmonary embolism emphasizes a strategy that integrates clinical findings with a variety of diagnostic modalities. 1–4 The optimal approach to treatment (primary therapy with thrombolysis or embolectomy versus secondary prevention with anticoagulation alone) is somewhat controversial. Risk stratification has emerged as the key concept in planning the treatment of patients with pulmonary embolism. Because pulmonary embolism is difficult to diagnose, expensive to treat, and occasionally lethal despite therapy, utilization of primary preventive measures is extraordinarily important. 5 Fortunately, a variety of effective mechanical measures and pharmacologic agents can be employed. Primary prophylaxis is cost effective. For every 1 000 000 patients undergoing operation who receive primary prophylaxis against DVT and pulmonary embolism, approximately US$60 000 000 can be saved in direct healthcare costs. Pathophysiology The most spectacular advance in the molecular medicine of venous thrombosis is the discovery of a specific genetic mutation, termed factor V Leiden, which predisposes to pulmonary embolism and DVT. This mutation results from a single nucleotide substitution of adenine for guanine 1691, which replaces the amino acid arginine with [...]... Pulmonary artery dilatation Decreased inspiratory collapse of inferior vena cava Right heart catheterization and pulmonary angiography Before undertaking diagnostic pulmonary angiography, accurate and high quality recordings of right heart pressures and waveforms should be obtained A carefully performed right heart catheterization may provide important clues to alternative diagnoses such as cardiac tamponade... of a duodenal ulcer 3 years previously At age 36 years he presented with syncope accompanied by tachycardia and diaphoresis His electrocardiogram at that time was notable for atrial fibrillation and inverted T waves in leads V1–V3 Five years later he complained of exertional dyspnea A lung scan demonstrated a high probability of pulmonary embolism At that time his mean pulmonary arterial pressure was... Right heart catheterization and pulmonary angiography were repeated, as part of a preoperative evaluation for planned pulmonary thromboendarterectomy Catheterization demonstrated a right atrial pressure of 10 mmHg, right ventricular pressure 55/10 mmHg, and pulmonary arterial pressure 55/ 28 mmHg, with a mean pulmonary arterial pressure of 35 mmHg Pulmonary angiography (Figure 14. 8a) revealed total occlusion... DIC, disseminated intravascular coagulation; PTT, partial thromboplastin time; rt-PA, recombinant tissue-type plasminogen activator 461 Cardiology Core Curriculum pulmonary arterial thrombus It consists of a 10 F steerable catheter with a suction cup attached at the tip Because of the cup’s large size, a surgical venotomy is utilized, usually in the right internal jugular vein A steerable handle controls... thrombocytopenia are the major side effects of shortterm unfractionated heparin administration When unfractionated heparin is administered chronically (the usual case when pulmonary embolism is being treated during pregnancy), heparin associated osteopenia may develop Oral anticoagulation with warfarin can be started as soon as the partial thromboplastin time is within the therapeutic range Patients should... catheter through the right cardiac chambers and the pulmonary arterial branches If catheter based strategies fail, then emergent surgical embolectomy with cardiopulmonary bypass can be undertaken.20 A non-randomized comparison of recombinant tissue-type plasminogen activator thrombolysis versus surgical embolectomy indicated that both approaches can be lifesaving in the majority of patients with massive... demonstrated a large right lower lobar pulmonary embolism (Figure 14.7) Therefore, she was maintained on continuous intravenous heparin for her entire pregnancy and was anticoagulated with warfarin postpartum Her delivery was entirely unremarkable and she was discharged home uneventfully Case 14.2 A 53-year-old man presented with gradually worsening dyspnea on exertion He complained of fatigue and inability... myocardial infarction, sepsis, or almost any other systemic illness Therefore, the plasma D-dimer ELISA is best utilized when suspected pulmonary embolism patients have no coexisting acute systemic illness The usual D-dimer measurement obtained in hospital laboratories employs a latex agglutination assay to detect disseminated intravascular coagulation Unlike the ELISA, the latex agglutination assay... thrombosis, especially among patients who already have subclinical hypercoagulable states These conditions include surgery, immobilization, trauma, obesity, increasing age, oral contraceptives, pregnancy, cancer (particularly occult adenocarcinoma), stroke, spinal cord injury, and indwelling central venous catheters Of course, patients who have had a prior pulmonary embolism or DVT are particularly susceptible... catheter embolectomy in the interventional laboratory Overall diagnostic strategy An integrated diagnostic approach is advocated, which combines clinical assessment, lung scanning, and evaluation for DVT This strategy narrows the number of patients who require pulmonary angiography Often, a definitive diagnosis can be obtained by combining clinical likelihood, plasma D-dimer ELISA, leg ultrasonography, . of an individual with metastatic cardiac tumor is poor, and therapy is generally palliative. In rare cases, cardiac invasion Pericardial disease, disease of the aorta, and heart tumors 441 may. patients with cancer of the lung, breast, melanoma, leukemia, and lymphoma. Metastases arising from Kaposi’s sarcoma have been found in patients with AIDS. Metastatic cardiac tumors may invade. light- headedness and syncope often occur. The physical examination of a patient with left atrial myxoma may demonstrate the stigmata of peripheral systemic emboli and an abnormal cardiac examination. In early