Abu Zubair meriwayatkan dari Jabir bin Abdullah bahwa Nabi Muhammad SAW bersabda:

"Setiap penyakit ada obatnya. Jika obat yang tepat diberikan dengan izin Allah, penyakit itu akan sembuh".

(HR. Muslim, Ahmad dan Hakim).

Senin, 22 Februari 2010

Pericarditis, Constrictive-Effusive


Effusive-constrictive pericarditis is a clinical syndrome characterized by concurrent pericardial effusion and pericardial constriction where constrictive hemodynamics are persistent after the pericardial effusion is removed. The mechanism of effusive-constrictive pericarditis is thought to be visceral pericardial constriction. Pericardial effusions vary in size and age and may be transudative, exudative, sanguineous, or chylous. An effusion persisting for months to years may evolve into effusive-constrictive pericarditis.1,2,3,4,5,6,7,8,9,10

The pericardium consists of two layers, a parietal layer and visceral layer. The visceral pericardium is composed of 1 or 2 cell layers of mesothelial cells and adheres closely with the epicardium. The parietal pericardium is separated from the visceral pericardium by a small amount of fluid that serves as a lubricant. Any supraphysiological accumulation of this fluid is identified as a pericardial effusion.1,2,11,12,13 In general, a pericardial effusion should be evaluated to determine its etiology and hemodynamic significance.

Patients with effusive-constrictive pericarditis may present with symptoms caused from a limitation of intercardiac end-diastolic volume. These findings are secondary to not only the pericardial effusion but also pericardial constriction. Symptoms, as well as history and physical findings, vary and a moderate-to-large pericardial effusion may occur.

Jugular venous and arterial pressures may be within the reference range, with or without signs of cardiac tamponade. This syndrome can evolve as part of a clinical continuum initiated by pericarditis or a pericardial effusion; thus, its etiologies mirror those of pericarditis, pericardial tamponade, and chronic constrictive pericarditis (see Pericarditis, Constrictive). The hemodynamic definition of this syndrome is the continued elevation of right atrial, end-diastolic right ventricular and left ventricular diastolic pressures after the removal of pericardial fluid returns the pericardial pressure to zero (or near zero).1,3,14

Recognition of effusive-constrictive pericarditis is clinically important because treatment with pericardiocentesis or a pericardial window may be inadequate as it would not address the visceral pericardium. Rather, a visceral pericardiectomy may be indicated for optimal therapy since it is the visceral pericardium that is constricting.

Importantly, not all cases of effusive-constrictive pericarditis progress to chronic constrictive pericarditis. In some clinical situations, relief from the effusion is obtained by means of pericardiocentesis or a pericardial window, and medical treatment is used to manage the underlying condition. The constriction may be transitory and surgical pericardiectomy may be avoided. These situations usually occur in the first months of a chronic effusion and close monitoring is required.

The effusive-constrictive variant of pericarditis was first described in the 1960s. Hancock popularized this definition of a constrictive physiology with a coexisting pericardial effusion.3 In 2004, Sagrista-Sauldea et al reported 15 subjects from Barcelona, Spain who were identified as having effusive-constrictive pericarditis.14 These individuals were among 190 consecutive subjects with clinical tamponade who underwent pericardiocentesis and concurrent catheterization. The etiologies of the effusive-constrictive pericarditis were infectious causes, irradiation, cardiac surgery, and idiopathic. Consistent with Hancock's data, Sagrista-Sauldea reported that most cases were due to idiopathic factors.

Constrictive pericarditis and cardiac tamponade both restrict filling of the cardiac chambers, thereby increasing both systemic and pulmonary filling pressures. In tamponade, single forward flow occurs during systole (prominent x descent in atrial pressure tracings), whereas in constriction, a biphasic pressure tracing is greater during diastole (prominent y descent). Patients with effusive-constrictive pericarditis may have tamponadelike pressure tracings, which change to constrictivelike tracings after pericardiocentesis. This is because the visceral pericardium, not the parietal, is constrictive. In rare cases, a loculated effusion may lead to constriction with regional tamponade of 1 or more cardiac chambers. Almost any form of chronic pericardial effusion has the potential to organize into an effusive-constrictive state even though the absolute number of cases is relatively low.4

Effusive-constrictive pericarditis may be part of a clinical continuum. Stages of infective pericarditis have been observed that range from acute pericarditis and tamponade with effusion to constrictive pericarditis without effusion. Effusive-constrictive pericarditis is likely a middle phase in this evolution. Therefore, suspicion for this entity should be high in cases of indolent, subacute pericarditis, as well in cases of chronic pericardial effusion.
United States

Effusive-constrictive pericarditis is a rare disorder. As a complication of pericarditis, pericardial effusion, pericardial tamponade, or chronic constrictive pericarditis, the incidence of effusive-constrictive pericarditis is proportional to the incidence of each of these entities. Cases in the United States are more often secondary to irradiation, cardiac surgery, uremia, or malignancy, or are idiopathic (see Differentials).6

Effusive-constrictive pericarditis is a rare disorder. As a complication of pericarditis, pericardial effusion, pericardial tamponade, or chronic constrictive pericarditis, the incidence of effusive-constrictive is proportional to the incidence of each of these entities. Cases in the developing countries are more often secondary to infectious causes (eg, tuberculosis) than other causes (see Differentials).15 In a prospective study of 1184 patients with pericarditis, Sagrista-Sauldea et al reported that 6.9% of 218 patients with tamponade had confirmed effusive-constrictive pericarditis.14

* The mortality of effusive-constrictive disease is directly related to its etiology. For example, patients with metastatic carcinoma in the pericardial space usually have a prognosis much poorer than that of patients with postviral or idiopathic pericardial effusion with constriction.
* Constrictive physiology increases the risk of morbidity, but no definitive statistics are available.
* Noncardiac metastatic effusions are often end-stage, with reported mortality rates of 47% and 80% at 3 and 6 months, respectively.


No reported racial predilection exists.

No reported sex predilection exists.

Since the incidences of many of the diseases that can cause effusive-constrictive pericarditis occur more frequently in older age groups, an age association exists. However, this disease can affect people of any age.

* Symptoms of effusive-constrictive pericarditis can be hard to interpret but may include atypical or typical chest pain, chest heaviness, or pressure.
* Other symptoms include dyspnea on exertion, fatigability, or peripheral edema.
* Many patients are asymptomatic until the advanced stages of disease. In more severe cases, impaired mental status may be evident as a result of decreased cardiac output.
* Specific etiologies of effusive-constrictive pericarditis may have characteristic antecedent histories that may suggest pericardial disease (eg, tuberculosis, renal failure, malignancy, radiation therapy, cardiovascular surgery).2


* Physical findings may be a continuum, including findings common with cardiac tamponade (see Cardiac Tamponade).16
* Findings may include hypotension, jugular venous distension, and diminished heart sounds (classic Beck triad).
* Other common findings may include pulsus paradoxus (paradoxical pulse), jugular venous pulse with a prominent x descent and absent y descent, tachycardia, tachypnea, hepatomegaly, ascites, peripheral edema, pleural effusion (in the absence of left-sided congestive signs), renal dysfunction, liver dysfunction and/or auscultation of a pericardial friction rub.
* The classic description of percussible cardiac dullness at the apex may be unreliable.
* Careful attention to all physical findings is required to find clues as to the underlying etiology of the pericardial disease.


Because effusive-constrictive pericarditis is rare, the differential diagnosis is guided by few published series and case reports (see Pericarditis, Constrictive). Effusive-constrictive pericarditis likely occurs at any point along a clinical continuum, from the occurrence of an effusion to the development of chronic pericardial constriction.

* Leading causes
o Idiopathic factors
o Irradiation
o Cardiac surgery
o Neoplasm - Most commonly lung, breast, or hematologic
o Infectious disease - Particularly in immunocompromised states (most commonly tuberculosis and fungal, although streptococcus species have been reported)17,18
o Myocardial infiltration
o Connective tissue disease
o Uremia
* The etiology can often be suspected from the clinical setting in which the effusion occurs.
* The differential diagnosis of effusive-constrictive pericarditis requires a consideration of all the causes for pericardial effusions and pericardial tamponade and then a determination if the particular patient has constrictive physiology.


Pericarditis, Constrictive


The thousand mysteries around us would not trouble but interest us, if only we had cheerful, healthy hearts.


If we all had healthy hearts, the mysteries of the heart would not trouble us; however, constrictive pericarditis certainly has been a mystery and remains a diagnostic challenge to this day.

The history of constrictive pericarditis is replete with some of the most famous names in medicine. Richard Lower described a patient with dyspnea and an intermittent pulse in 1669. Lancisi first reported on the constrictive syndrome in 1828. Corrigan described the pericardial knock in 1842. Kussmaul described his sign and the associated paradoxical pulse in 1873.1,2,3

Constrictive pericarditis has symptoms that overlap a variety of diseases as diverse as myocardial infarction, aortic dissection, pneumonia, influenza, and connective tissue disorders. This overlap can confuse the most skilled diagnostician. An increased suspicion for constriction helps move it to the top of the broad differential diagnosis and provides for a correct diagnosis and timely therapy.

Constrictive pericarditis occurs when a thickened fibrotic pericardium, of whatever cause, impedes normal diastolic filling. This usually involves the parietal pericardium, although it can involve the visceral pericardium (see Pericarditis, Constrictive-Effusive). Acute and subacute forms of pericarditis (which may or may not be symptomatic) may deposit fibrin, which may, in turn, evoke a pericardial effusion. This often leads to pericardial organization, chronic fibrotic scarring, calcification, and restricted cardiac filling.4

The classic diagnostic conundrum of constrictive pericarditis is the difficulty in distinguishing it from restrictive cardiomyopathy (see Cardiomyopathy, Restrictive) and other syndromes associated with elevated right-sided pressures that all share similar symptoms, physical findings, and hemodynamics. Although obtaining a careful history and performing a physical examination remain the cornerstones of evaluation, technologic advances have facilitated diagnosis, particularly with the appropriate use of Doppler echocardiography, high-resolution computed tomography (CT), magnetic resonance imaging (MRI), and invasive hemodynamic measurement.

The normal pericardium is composed of 2 layers: the tough fibrous parietal pericardium and the smooth visceral pericardium. Usually, approximately 50 mL of fluid (plasma ultrafiltrate) is present in the intrapericardial space to minimize friction during cardiac motion.5

Acute and subacute forms of pericarditis (which may or may not be symptomatic) may deposit fibrin, which may, in turn, evoke a pericardial effusion. This often leads to pericardial organization, chronic fibrotic scarring, and calcification, most often involving the parietal pericardium (see Pericarditis, Constrictive-Effusive).6

This thickened fibrotic pericardium, regardless of cause, impedes normal late diastolic filling, distinguishing constrictive from restrictive pericarditis. Since the myocardium is unaffected, early ventricular filling during the first third of diastole is unimpeded, but afterwards, the stiff pericardium affects flow and hemodynamics. In other words, the ventricular pressure decreases rapidly early (producing a steep y descent on right atrial pressure waveform tracings) and then increases abruptly to a level that is sustained until systole ("dip-and-plateau waveform" or "square root sign" seen on right or left ventricular pressure waveform tracings).7

The clinical symptoms and classic hemodynamic findings can be explained by early rapid diastolic filling and elevation and equalization of the diastolic pressures in all of the cardiac chambers restricting late diastolic filling, leading to venous engorgement and decreased cardiac output, all secondary to a confining pericardium.

United States

Similar to many diseases that in the past were predominantly infectious in origin, the clinical spectrum of constrictive pericarditis has changed in recent years. Approximately 9% of patients with acute pericarditis for any reason go on to develop constrictive physiology.8 T he true frequency is therefore dependent on the incidence of the specific causes of pericarditis, but since acute pericarditis is only clinically diagnosed in 1 in 1,000 hospital admissions, the frequency of a diagnosis of constrictive pericarditis is less than 1 in 10,000 hospital admissions.


In the developing world, infectious etiologies remain more prominent (tuberculosis has the highest total incidence).

* Scant data exist because the disease is rare.
* The underlying disease usually determines the prognosis. Poorer prognoses are associated with malignancy and New York Heart Association (NYHA) class III or IV heart failure symptoms.
* Long-term survival after pericardiectomy depends on the underlying cause. Of common causes, idiopathic constrictive pericarditis has the best prognosis (88% survival at 7 years), followed by constriction due to cardiac surgery (66% at 7 years). The worst postpericardiectomy prognosis occurs in postradiation constrictive pericarditis (27% survival at 7 years). This likely represents confounding comorbidities. Predictors of poor outcomes in patients who undergo pericardiectomy including history of prior radiation, worsening renal function, pulmonary hypertension, systolic heart failure, hyponatremia, and advanced age.9


* No race predilection exists for this disorder.


* Most likely a male predominance exists, with a male-to-female ratio of 3:1 in some studies.


* Cases have been reported in persons aged 8-70 years. Predilection is likely reflective of the underlying disease.
* Historical studies suggest a median age of 45 years, while more recent studies suggest a median age of 61 years. This likely reflects a demographic change that is likely to continue.


* Constrictive pericarditis presents with a myriad of symptoms, making a diagnosis based solely on clinical history virtually impossible. Additionally, these symptoms may develop slowly over a number of years such that patients may not be aware of all of their symptoms until questioned.
* Dyspnea tends to be the most common presenting symptom and occurs in virtually all patients. Fatigue and orthopnea are common.
* Lower-extremity edema and abdominal swelling and discomfort are other common symptoms. Nausea, vomiting, and right upper quadrant pain, if present, are thought to be due to hepatic congestion, bowel congestion, or both.
* The initial history may be more compatible with liver disease (cryptogenic cirrhosis) than with pericardial constriction because of the predominance of findings related to the venous system.
* Chest pain, presumably due to active inflammation, may be present, although this is observed in a minority of patients.


* General findings
o In the early stages, physical findings may be subtle, requiring close examination to avoid missing the diagnosis.
o In more advanced stages, the patient may appear ill, with marked muscle wasting, cachexia, or jaundice.
o Constriction should be considered in the presence of otherwise unexplained jugular venous distention, pleural effusion, hepatomegaly, or ascites.
* Cardiovascular findings
o Elevated jugular venous pressures are an almost universal finding.
o Avoid examining the patient only in the supine position because venous pressures may be above the angle of the jaw and inadvertently mistaken for normal.
o Sinus tachycardia is common while the blood pressure is normal or low, depending on the stage of the disease process.
o The apical impulse is often impalpable, and the patient may have distant or muffled heart sounds.
o A pericardial knock, which corresponds with the sudden cessation of ventricular filling early in diastole, occurs in approximately half the cases and may be mistaken for an S3 gallop. However, a knock is of higher frequency than an S3 and occurs slightly earlier in diastole.
o A cardiac murmur is typically not present unless concomitant valvular heart disease or a fibrous band that constricts the right ventricular outflow tract is present.
o Pulsus paradoxicum (paradoxus) is a variable finding and, if present, rarely exceeds 10 mm Hg unless a concomitant pericardial effusion with an abnormally elevated pressure exists.
o The Kussmaul sign (ie, elevation of systemic venous pressures with inspiration) is a common nonspecific finding, but this sign is also observed in patients with right ventricular failure, restrictive cardiomyopathy, right ventricular infarction, and tricuspid stenosis, although, importantly, not in patients with cardiac tamponade.
* Gastrointestinal, pulmonary, and other organ system findings
o Hepatomegaly with prominent hepatic pulsations can be detected in as many as 70% of patients.
o Other signs that result from chronic hepatic congestion include ascites, spider angiomata, and palmar erythema, which can contribute to the common but erroneous diagnosis of primary liver disease.
o Peripheral edema is a common finding, although it may be less prominent in younger patients with competent venous valves.


The varied etiologies of constrictive pericarditis parallel those of acute pericarditis (see Pericarditis, Acute), which is a common precipitant. All forms of pericarditis may eventually lead to pericardial constriction. Generally, these can be broken down by frequency into common, less common, and rare forms. The top 3 causes of constrictive pericarditis are idiopathic (presumably viral), postcardiothoracic surgery, and irradiation therapy, which, according to a recent study, are responsible for 46%, 37%, and 9%, respectively, of cases of constrictive pericarditis (in patients who underwent surgical therapy).9

* The following are common etiologies:
o Idiopathic: In many cases, particularly in developed countries, no antecedent diagnosis can be found. These cases are termed idiopathic. Reports by many authors indicate that a high percentage of idiopathic cases of constrictive pericarditis may be related to previously recognized or unrecognized viral pericarditis. Of the viruses, coxsackievirus A and B, other echoviruses, and adenoviruses are most commonly implicated.8
o Infectious (bacterial): Tuberculosis is the leading cause of constrictive pericarditis in developing nations but represents only a minority of causes in the United States and other developed countries. Bacterial infections that lead to purulent pericarditis are also declining in frequency. In the past, purulent pericarditis associated with pneumococcal pneumonia was the most common presentation of a bacterial source. However, the widespread use of antibiotics has drastically changed the frequency and spectrum of purulent pericarditis such that the most common presentation now occurs following cardiac surgery. An increasing number of gram-positive organisms, including multiple resistant strains of staphylococci, may be isolated. Group A and B streptococci and gram-negative rods (eg, Pseudomonas species, Escherichia coli, and Klebsiella species) have also been documented.
o Infectious (viral [see also Idiopathic]): Coxsackievirus, hepatitis, adenovirus, and echovirus.
o Radiation-induced: The long-term effects of thoracic and mediastinal radiation therapy (eg, used in the treatment of hematological, breast, and other malignancies) are being increasingly realized. The common features of radiation-induced cardiac complications stem from microcirculation injury with endothelial damage, capillary rupture, and platelet adhesion. This sets up an inflammatory response, which may either resolve or organize to form adhesions between the visceral pericardium and the parietal pericardium, which leads to constriction. Generally, radiation-induced constrictive pericarditis presents 5-10 years after radiation therapy and is more likely to present with an associated pericardial effusion. In a study by Bertog in 2004, the median time between radiation and pericardiectomy was 11 years, with a broad range of 2-30 years, which is consistent with other previous studies.9
o Postsurgical: Any operative or invasive (catheterization) procedure in which the pericardium is opened, manipulated, or damaged may invoke an inflammatory response, leading to constrictive pericarditis. The most common example is constrictive pericarditis in the setting of previous coronary artery bypass grafting.
* The following are less common etiologies:
o Infectious (fungal): Fungal infections are an uncommon source of constrictive pericarditis in patients who are immunocompetent. Nocardia species can be causative organisms, especially in endemic areas such as the Ohio Valley. Aspergillus, Candida, and Coccidioides species are important pathogens in patients infected with HIV and in other immunocompromised hosts.
o Neoplasms: Malignant involvement may also manifest as pericardial effusion (with or without tamponade) or as an encased heart with thickening of both visceral and parietal layers, resulting in constrictive physiology. Although many types of neoplasms have been reported, breast and lung carcinomas and lymphomas are the most common metastatic malignancies associated with constrictive pericarditis. Other malignancies that involve the pericardium with relative frequency include melanoma and mesothelioma.
o Uremia: Constrictive pericarditis may develop in association with long-term hemodialysis.
o Connective tissue disorders: Autoimmune disorders that involve the pericardium are not unusual, typically manifesting as a small pericardial effusion or as an episode of acute pericarditis. Chronic pericardial involvement is less common but can occur in patients with rheumatoid arthritis, usually associated with the presence of subcutaneous nodules. Systemic lupus erythematosus and scleroderma also may lead to constrictive pericarditis, and, in the latter, this carries a poor prognosis.
o Drug-induced: Procainamide and hydralazine have been reported to cause constrictive pericarditis through a drug-induced lupuslike syndrome. Methysergide therapy also has been implicated as a cause of constrictive pericarditis.
o Trauma: Although uncommon, both blunt and penetrating trauma to the chest wall have been reported to cause constrictive pericarditis, presumably through an inflammatory mechanism.
o Myocardial infarction: Postmyocardial infarction constrictive pericarditis has been reported. The patient typically has a history of Dressler syndrome or hemopericardium after thrombolytic therapy.
* The following are rare etiologies:
o Toxic or metabolic: Uremia with chronic hemodialysis can lead to constrictive pericarditis and is usually associated with a pericardial effusion.
o Intrapericardial instrumentation: Constrictive pericarditis after implantation of an epicardial pacemaker or automated implantable cardiac defibrillator is a rare but reported phenomenon.
o Hereditary: Mulibrey nanism is an autosomal recessive disorder characterized by multiple abnormalities, including dwarfism, constrictive pericarditis, abnormal fundi, and fibrous dysplasia of the long bones.
o Chemical trauma: Constrictive pericarditis following sclerotherapy for esophageal varices is rare.
o Chylopericardium: This is a rare cause of constrictive pericarditis.




Aortitis is literally inflammation of the aorta, and it is representative of a cluster of large-vessel diseases that have various or unknown etiologies. While inflammation can occur in response to any injury, including trauma, the most common known causes are infections or connective tissue disorders. Infections can trigger a noninfectious vasculitis by generating immune complexes or by cross-reactivity. The etiology is important because immunosuppressive therapy, the main treatment for vasculitis, could aggravate an active infectious process.

Inflammation of the aorta can cause aortic dilation, resulting in aortic insufficiency. Also, it can cause fibrous thickening and ostial stenosis of major branches, resulting in reduced or absent pulses, low blood pressure in the arms, possibly with central hypertension due to renal artery stenosis. Depending on what other vessels are involved, ocular disturbances, neurological deficits, claudication, and other manifestations of vascular impairment may accompany this disorder.

Agents known to infect the aorta include Neisseria (eg, gonorrhea), tuberculosis, Rickettsia (eg, Rocky Mountain spotted fever) species, spirochetes (eg, syphilis), fungi (eg, aspergillosis, mucormycosis), and viruses (eg, herpes, varicella-zoster, hepatitis B, hepatitis C).

Immune disorders affecting the aorta include Takayasu arteritis, giant cell arteritis, polyarteritis nodosa, Behcet disease, Cogan syndrome, sarcoidosis, spondyloarthropathy, serum sickness, cryoglobulinemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, Henoch-Schönlein purpura, and postinfectious or drug-induced immune complex disease.

Also, anti-neutrophil cytoplasmic autoantibody (ANCA) can affect the large vessels, as in Wegener granulomatosis, polyangiitis, and Churg-Strauss syndrome. Other antibodies such as anti-glomerular basement membrane (ie, Goodpasture syndrome) and anti-endothelial (ie, Kawasaki disease) also can be culprits. Transplant rejection, inflammatory bowel diseases, and paraneoplastic vasculitis also may afflict the large vessels.

The cause or causes of giant cell or temporal arteritis, Takayasu arteritis, and polyarteritis nodosa are unknown.

The disease has 3 phases. Phase I is the prepulseless inflammatory period characterized by nonspecific systemic symptoms including low-grade fever, fatigue, arthralgia, and weight loss. Phase II involves vascular inflammation associated with pain (eg, carotidynia) and tenderness over the arteries. Phase III is the fibrosis stage, with predominant ischemic symptoms and signs secondary to dilation, narrowing, or occlusion of the proximal or distal branches of the aorta. Bruits frequently are heard, especially over carotid arteries and the abdominal aorta. The extremities become cool, and pain develops with use (ie, arm or leg claudication). Even in phase III, a significant number of patients seem to have insidious vascular inflammation, which has been demonstrated in surgical specimens and postmortem series.

In advanced cases, occlusion of the vessels to the extremities may result in ischemic ulcerations or gangrene, and with the involvement of cerebral arteries, strokes can occur. Because of the chronic nature of the disease, however, collateral circulation usually develops in the areas involved by vasculitis.

Pathologic changes involved in Takayasu arteritis are the same as for giant cell arteritis. Involved vessel walls develop irregular thickening and intimal wrinkling. Early in the disease, mononuclear infiltration with perivascular cuffing is seen. That extends to the media, followed by granulomatous changes and patches of necrosis and scarring (fibrosis) of all layers, especially the intima. Late stages have lymphocytic infiltration.

The distinction between Takayasu and giant cell arteritis is primarily the clinical pattern of vessels involved. Giant cell arteritis commonly involves the temporal artery, whereas Takayasu arteritis primarily involves the aorta, its main branches, and, in 50% of cases, the pulmonary artery. The initial vascular lesions frequently occur in or at the origin of the left subclavian artery, which can cause weakened radial pulse and easy fatigability in the left arm. As the disease progresses, the left common carotid, vertebral, brachiocephalic, right-middle or proximal subclavian, right carotid, and vertebral arteries, as well as the aorta, also are affected, as well as retinal vessels.

When the abdominal aorta and its branches, eg, the renal arteries, are involved, central hypertension may develop. Accurate blood pressure measurement may be difficult because of arterial lesions affecting supply to the extremities.

Varying degrees of narrowing and occlusion or dilation of involved portions of the arteries result in a wide variety of symptoms.
United States

In the United States and Europe, incidence is 1-3 new cases per year per million population. In a cohort of 1204 surgical aortic specimens described by Rojo-Leyva et al1 , 168 (14%) had inflammation and 52 (4.3%) were classified as having idiopathic aortitis. Among 383 individuals with thoracic aortic aneurysms, 12% had idiopathic aortitis.

Vasculitis has a worldwide distribution, with the greatest prevalence among Asians. An extensive epidemiological study conducted in Japan in 1984 identified 20 cases per million population. In 1990, Takayasu arteritis was added to the list of intractable diseases maintained by the Japanese Ministry of Health and Welfare; by the year 2000, 5000 patients were registered (the reported prevalence increased 2.5-fold).

The 2 major predictors of poor outcome are complications (eg, Takayasu retinopathy, hypertension, aortic regurgitation, aneurysm) and progressive course.

* Patients with no complications or with mild to moderately severe complications have a 10-year survival rate of 100% and a 15-year survival rate of 93-96%. With notable complications or progression, the 10-year survival rate is 80-90% and the 15-year survival rate is 66-68 %.
* The occurrence of both a major complication and progressive course predicts the worst outcome (43% survival rate at 15 y).


Vasculitis is most common among women of reproductive age (female cases outnumber male at a ratio of 9:1).

Aortitis is most commonly discovered at age 10-40 years.

In 1905, at the 12th Annual Meeting of the Japanese Ophthalmology Society, Mikito Takayasu, an ophthalmologist, described a 21-year-old Japanese woman with a peculiar retinal arteriovenous anastomosis. At the same meeting, Onishi described a patient with similar funduscopic findings and absence of radial pulses. Giovan B. Morgagni, an Italian pathologist, reported the first case with signs and symptoms consistent with Takayasu arteritis. In 1948, Shimizu and Sano described a condition characterized by absent pulses, peripapillary arteriovenous anastomosis of the retina, and accelerated carotid sinus reflex, which they called pulseless disease. The name "Takayasu's disease" was applied by Caccamis in 1954, and that eponym held.

* Vanoli et al2 reported a study of 104 Italian patients (91 female, 13 male) with Takayasu arteritis. Median delay in diagnosis was 15.5 months. The main clinical features and laboratory findings were arterial bruit (90%), decreased or absent pulse (85%), blood pressure deference over 10 mm Hg (70%), claudication of extremities (45%), hypertension (40%), asthenia (50%), fever (30%), arthralgia/arthritis (25%), weight loss over 5 kg (20%), headache (20%), erythrocyte sedimentation rate greater than 30 mm/hr (85%), anemia (60%), and leukocytosis (20%). Vascular involvement based on full aortography revealed involvement of the left subclavian (65%), right subclavian (52%), left carotid (44%), abdominal aorta (39%), and right carotid (36%).
* Many patients have ischemia of the upper extremities that may manifest as arm claudication or numbness at the time of disease recognition. Claudication of the lower limbs is less common as a presenting symptom.
* Hall et al3 reported arthralgias or myalgias in about one half of patients at the early stage of disease. Symmetric inflammatory polyarthritides resembling rheumatoid arthritis were observed in 5 of 32 patients. Articular symptoms were either transient or continual for several months or longer. Myalgia sometimes dominates the clinical presentation and may mislead clinicians.
* Neurologic symptoms are generally caused by decreased cerebral blood flow in the carotid and vertebral arteries. Neurologic manifestations include vertigo, syncope, orthostasis, headaches, convulsions, transient ischemic attacks, stroke, and dementia. Seizures are often attributed to hypertensive encephalopathy. Because of central retinal hypoperfusion, visual impairment is most often bilateral and 48% of patients with vertebral artery involvement and 40% with common carotid artery involvement have visual aberrations.
* In a minority of cases (8-18% of pooled series), skin lesions resembling erythema nodosum or pyoderma gangrenosum were found over the legs. Upon biopsy, the lesions frequently showed vasculitis of the small vessels. Erythema nodosum is the predominant dermatologic finding in the United States and Europe, whereas pyoderma gangrenosum is found more frequently in Japan. Raynaud phenomenon has also been reported in 8-14% of patients.
* Angina pectoris occurs as a result of coronary artery ostial narrowing from aortitis or coronary arteritis and can lead to myocardial infarction, heart failure, or sudden death. Congestive heart failure may be caused by valvular disease. Aortic regurgitation that results from dilation of the aortic root is common.
* In cases of documented pulmonary artery involvement, fewer than 25% of patients had related clinical manifestations and only 20% had pulmonary hypertension. Pulmonary symptoms include cough, dyspnea, and hemoptysis.
* Abdominal pain, diarrhea, and gastrointestinal hemorrhage may result from mesenteric artery ischemia, but this is rare.
* Specific arteries that are inflamed may be tender to the touch (eg, carotid, temporal).


Patients frequently appear chronically ill. Mild to moderate fever may be present. Heart rate and rhythm are unaffected. Reduced blood pressure in one or both arms is common. Laterality of blood pressure (ie, a difference between left and right arms greater than 10 mm Hg) suggests vascular obstruction, and the difference may be greater than 30 mm Hg. Maneuvers can distinguish this pressure drop and/or pulse weakness from scalenus anticus syndrome, in which arm elevation and turning of the head are influential.

* Arterial pulse intensity in any of the limbs may be diminished, often asymmetrically. Bruits may be audible over the carotid arteries, abdominal aorta, and sometimes the subclavian and brachial arteries. In a North American study by Kerr et al, bruit was the most common clinical finding (80%), and the most common site was in the carotid vessels (70%). A diastolic decrescendo murmur may signal aortic valve insufficiency. The cardiac apex may be displaced laterally. Rales, edema, liver congestion, elevated venous pressure, and hepatojugular reflux, if present, signify the complication of heart failure.
* Hypertension develops in 33-76% of patients, most frequently resulting from narrowing of the renal artery, but narrowing and decreased elasticity of the aorta and branches also can be exacerbating factors. As narrowing or occlusion may lower the pressure in the arms, all limbs must be checked, and measuring central pressure by catheterization may be required to identify hypertension.
* Synovitis mimicking rheumatoid arthritis may be noticeable over larger joints, such as the knees or wrists, early in the course of disease.


The pathogenesis of Takayasu arteritis has not been elucidated completely. Genetic influences and immunological mechanisms have received the most attention. The associations of Takayasu arteritis with other autoimmune diseases, such as connective tissue diseases and ulcerative colitis, provide clinical support for the importance of autoimmunity in the pathogenesis.

* High titers of anti-endothelial antibodies were detected in patients clinically diagnosed as having Takayasu arteritis.
o In a study of 19 patients by Eichorn et al4 , anti-endothelial antibodies were found in 18, and the titers were approximately 20 times higher than normal. Chauhan et al5 showed that the antibodies are directed against 60-65 kd antigens and may induce expression of endothelial adhesion molecules, cytokine production, and apoptosis.
o The only patient who did not have a positive titer for the antibody had inactive disease. However, whether this antibody is pathogenic or merely an epiphenomenon secondary to the vascular injury remains unclear.
o The presence of elevated anti-cardiolipin antibody titer also has been reported.
* Cell-mediated immunological mechanisms are thought to be of primary importance.
o Histopathologic examination has shown heavily infiltrating cells in all layers of the aorta, including alpha-beta T cells, gamma-delta T cells, and natural killer (NK) cells.
o In comparison to the cells found in a patient with an atherosclerotic aortic aneurysm, the proportion of gamma-delta T cells (ie, cytotoxic cells) was exceedingly high.
o Enhanced expression of human leukocyte antigen (HLA) molecules and restricted usage of alpha-beta T-cell receptor genes and gamma-delta T-cell receptor genes in the infiltrating cells suggest the existence of a targeted specific antigen. Gamma-delta T cells can recognize the major histocompatability complex (MHC) class I (MIC) chain-related molecules MICA and MICB, whose expression is known to be increased by stress. The MICA gene was found to be located near the HLA-B gene. MICA-1.2 is strongly associated with Takayasu arteritis, even in the absence of HLA-B52, which is highly prevalent in Japanese patients. Expression of heat shock protein-65, a stress-induced protein, also is increased in the tissue. These findings suggest that unknown stress, such as infection, may trigger the autoimmune process involved in patients with Takayasu arteritis.


Aortic Dissection


Aortic dissection is defined as separation of the layers within the aortic wall. Tears in the intimal layer result in the propagation of dissection (proximally or distally) secondary to blood entering the intima-media space.

This disease was first described long ago (>200 y), but new challenges have arisen since the advent of advanced diagnostic and therapeutic modalities. The clinical manifestations are diverse, making the diagnosis difficult and requiring a high clinical index of suspicion.1,2,3

Aortic dissection can be diagnosed premortem or postmortem because many patients die before presentation to the emergency department (ED) or before diagnosis is made in the ED.

Aortic dissection is more common in males than in females, with a male-to-female ratio of 2:1. The condition commonly occurs in persons in the sixth and seventh decades of life.3 Patients with Marfan syndrome present earlier, usually in the third and fourth decades of life.

Aortic dissection. CT scan showing a flap (right ...
Aortic dissection. CT scan showing a flap (right side of image).


Aortic dissection. CT scan showing a flap (right ...

Aortic dissection. CT scan showing a flap (right side of image).

Aortic dissection. CT scan showing a flap (center...
Aortic dissection. CT scan showing a flap (center of image).


Aortic dissection. CT scan showing a flap (center...

Aortic dissection. CT scan showing a flap (center of image).

Aortic dissection. CT scan showing a flap (center...
Aortic dissection. CT scan showing a flap (center of image).


Aortic dissection. CT scan showing a flap (center...

Aortic dissection. CT scan showing a flap (center of image).

For more examples of aortic dissection visible on CT scans, see the Multimedia section.

History of the Procedure

Morgagni first described aortic dissection more than 200 years ago. The condition was associated with a high mortality rate before the introduction of the cardiopulmonary bypass in the 1950s, which led to aortic arch repair and construction.

Recent advancements in the field of stent placements and percutaneous aortic fenestrations have further reduced mortality rates. However, despite recent advancements, the mortality rate associated with aortic dissection remains high.1,3

An aortic dissection is a split or partition in the media of the aorta; this split is frequently horizontal or diagonal. An intimal tear connects the media with the aortic lumen, and an exit tear creates a true lumen and a false lumen. The true lumen is lined by intima, and the false lumen is within the media.

Aortic dissection. True lumen and false lumen sep...
Aortic dissection. True lumen and false lumen separated by an intimal flap.


Aortic dissection. True lumen and false lumen sep...

Aortic dissection. True lumen and false lumen separated by an intimal flap.

Typically, flow in the false lumen is slower than in the true lumen, and the false lumen often becomes aneurysmal when subjected to systemic pressure. The dissection usually stops at an aortic branch vessel or at the level of an atherosclerotic plaque.

An acute aortic dissection (<2 wk) is associated with high morbidity and mortality rates (highest mortality in the first 7 d) compared with chronic aortic dissection (>2 wk), which has a better prognosis.

In the United States, aortic dissection is an uncommon disease. The true prevalence of aortic dissection is difficult to estimate, and most estimates are based on autopsy studies. Evidence of aortic dissection is found in 1-3% of all autopsies (1 in 350 cadavers). The incidence of aortic dissection is estimated to be 5-30 cases per 1 million people per year. Aortic dissection occurs once per 10,000 patients admitted to the hospital; approximately 2,000 new cases are reported each year in the United States.4

* Arterial hypertension:3 Of patients with aortic dissection, 70% have elevated blood pressure.
* Aortic dilatation and wall thinning: Aortic aneurysm is defined as a pathologic dilatation of a segment of a blood vessel. A true aneurysm involves all 3 layers of the aortic wall.
* Iatrogenic: Aortic dissection can be caused by cardiac surgery, including aortic and mitral valve replacements, coronary artery bypass graft surgery, or percutaneous catheter placement (eg, cardiac catheterization, percutaneous transluminal coronary angioplasty). Aortic dissection occurs when the layers are split in the process of cannulation or aortotomy.
* Aortic atherosclerosis: Factors include cystic medial necrosis and aortic medial disease.
* Congenital aortic valve anomalies: These may include unicommissural or bicuspid aortic valves or aortic coarctation.
* Marfan syndrome
* Advanced age
* Pregnancy
* Ehlers-Danlos syndrome
* Syphilitic aortitis
* Deceleration injury possibly with related chest trauma
* Aortic arch hypoplasia
* Cocaine use


The aortic wall is continuous and is exposed to high pulsatile pressure and shear stress (the steep slope of the pressure curve, ie, the water hammer effect), making the aorta particularly prone to injury and disease from mechanical trauma. The aorta is more prone to rupture than any other vessel, especially with the development of aneurysmal dilatation, because its wall tension, as governed by the Laplace law (proportional to the product of pressure and radius), is intrinsically high.

An intimal tear connects the media with the aortic lumen, and an exit tear creates a true lumen and a false lumen. The true lumen is lined by intima, and the false lumen is lined by media. The true lumen is frequently smaller than the false lumen, but not invariably. The false lumen is indeed within the media, but suggesting that it is "lined" with it is misleading; if the aortic dissection becomes chronic, the lining becomes a serosal pseudointima. Typically, flow in the false lumen is slower than flow in the true lumen, and the false lumen often becomes aneurysmal when subjected to systemic pressure.

Aortic dissection. True lumen versus false lumen ...
Aortic dissection. True lumen versus false lumen in an intimal flap.


Aortic dissection. True lumen versus false lumen ...

Aortic dissection. True lumen versus false lumen in an intimal flap.

The dissection usually stops at an aortic branch vessel or at the level of an atherosclerotic plaque. Most classic aortic dissections begin at 1 of 3 distinct anatomic locations, including (1) the aortic arch, (2) approximately 2.2 cm above the aortic root, or (3) distal to the left subclavian artery.

Ascending aortic involvement may result in death from wall rupture, hemopericardium and tamponade, occlusion of the coronary ostia with myocardial infarction, or severe aortic insufficiency. The nervi vascularis (ie, bundles of nerve fibers found in the aortic adventitia) are involved in the production of pain.

DeBakey and coworkers classify aortic dissection into 3 types, as follows:

* Type I: The intimal tear occurs in the ascending aorta, but the descending aorta is also involved.
* Type II: Only the ascending aorta is involved.
* Type III: Only the descending aorta is involved.
o Type IIIA involves the descending aorta that originates distal to the left subclavian artery and extends as far as the diaphragm.
o Type IIIB involves the descending aorta below the diaphragm.

The Stanford classification has 2 types, as follows:

* Type A: The ascending aorta is involved (DeBakey types I and II).
* Type B: The descending aorta is involved (DeBakey type III).

This system also helps delineate treatment. Type A dissections usually require surgery, whereas type B dissections are managed medically under most conditions.5

Image A represents a Stanford A or a DeBakey type...
Image A represents a Stanford A or a DeBakey type 1 dissection. Image B represents a Stanford A or DeBakey type II dissection. Image C represents a Stanford type B or a DeBakey type III dissection. Image D is classified in a manner similar to A but contains an additional entry tear in the descending thoracic aorta. Note that a primary arch dissection does not fit neatly into either classification.


Image A represents a Stanford A or a DeBakey type...

Image A represents a Stanford A or a DeBakey type 1 dissection. Image B represents a Stanford A or DeBakey type II dissection. Image C represents a Stanford type B or a DeBakey type III dissection. Image D is classified in a manner similar to A but contains an additional entry tear in the descending thoracic aorta. Note that a primary arch dissection does not fit neatly into either classification.


Patients with acute aortic dissection present with the sudden onset of severe and tearing chest pain, although this description is not universal. Some patients present with only mild pain, often mistaken for a symptom of musculoskeletal conditions located in the thorax, groin, or back. Some patients present with no pain.6

Consider thoracic aortic dissection in the differential diagnosis of all patients presenting with chest pain. The pain is usually localized to the front or back of the chest, often the interscapular region, and typically migrates with propagation of the dissection.

The pain of aortic dissection is typically distinguished from the pain of acute myocardial infarction by its abrupt onset, although the presentations of the two conditions overlap to some degree and are easily confused. Aortic dissection can be presumed in patients with symptoms and signs suggestive of myocardial infarction but without classic ECG findings.

Presenting signs and symptoms in acute thoracic aortic dissection include the following:

Anterior chest pain is a manifestation of ascending aortic dissection. Neck or jaw pain is a manifestation of aortic arch dissection. Interscapular tearing or ripping pain is a manifestation of descending aortic dissection.

Neurologic deficits are a presenting sign in up to 20% of cases. Syncope is part of the early course of aortic dissection in approximately 5% of patients and may be the result of increased vagal tone, hypovolemia, or dysrhythmia.6 Cerebrovascular accident (CVA) symptoms include hemianesthesia and hemiparesis or hemiplegia.6 Altered mental status is also reported. Other causes of syncope or altered mental status include (1) CVA from compromised blood flow to the brain or spinal cord or (2) ischemia from interruption of blood flow to the spinal arteries.

Patients with peripheral nerve ischemia can present with numbness and tingling in the extremities, limb paresthesias, pain, or weakness.

Horner syndrome is caused by interruption in the cervical sympathetic ganglia and manifests as ptosis, miosis, and anhidrosis.

Hoarseness from recurrent laryngeal nerve compression has also been described.

Cardiovascular manifestations involve symptoms and signs suggestive of congestive heart failure6 secondary to acute severe aortic regurgitation or dyspnea, orthopnea, bibasilar crackles, or elevated jugular venous pressure. Signs of aortic regurgitation include bounding pulses, wide pulse pressure, and diastolic murmurs. Hypertension may result from a catecholamine surge or underlying essential hypertension.7,6 Hypotension is an ominous finding and may be the result of excessive vagal tone, cardiac tamponade, or hypovolemia from rupture of the dissection.

Other cardiovascular manifestations include findings suggestive of cardiac tamponade (eg, muffled heart sounds, hypotension, pulsus paradoxus, jugular venous distension); these may be present and must be recognized quickly. Superior vena cava syndrome can result from compression of the superior vena cava from a large, distorted aorta. Wide pulse pressure and pulse deficit or asymmetry of peripheral pulses is reported. Patients with right coronary artery ostial dissection may present with acute myocardial infarction, commonly inferior myocardial infarction. Pericardial friction rub may occur secondary to pericarditis.

Respiratory symptoms can include dyspnea and hemoptysis if dissection ruptures into the pleura or if tracheal or bronchial obstruction has occurred. Physical findings of a hemothorax may be found if the dissection ruptures into the pleura.

GI symptoms include dysphagia, flank pain, and/or abdominal pain. Dysphagia may occur from compression of the esophagus. Flank pain may be present if the renal artery is involved. Abdominal pain may be present if the dissection involves the abdominal aorta.

Other nonspecific clinical presentations include fever or anxiety and premonitions of death.8

Emergent surgical correction is the preferred treatment for the following classifications of aortic dissection:

* Stanford type A (DeBakey type I and II) ascending aortic dissection
* Complicated Stanford type B (DeBakey type III) aortic dissections with clinical or radiological evidence of the following conditions:
o Propagation (increasing aortic diameter)
o Increasing size of hematoma
o Compromise of major branches of the aorta
o Impending rupture
o Persistent pain despite adequate pain management
o Bleeding into the pleural cavity
o Development of saccular aneurysm

Relevant Anatomy

From outside to inside, the aorta is composed of the intima, media, and adventitia. The intima, the innermost layer, is thin, delicate, lined by endothelium, and easily traumatized.

The media is responsible for imparting strength to the aorta and is composed of laminated but intertwining sheets of elastic tissue. The arrangement of these sheets in a spiral provides the aorta with its maximum allowable tensile strength. The aortic media contains very little smooth muscle and collagen between the elastic layers and thus has increased distensibility, elasticity, and tensile strength. This contrasts with peripheral arteries, which, in comparison, have more smooth muscle and collagen between the elastic layers.

The outermost layer of the aorta is adventitia. This largely consists of collagen. The vasa vasorum, which supplies blood to the outer half of the aortic wall, lies within the adventitia. The aorta does not have a serosal layer.

The aorta plays an integral role in the forward circulation of the blood in diastole. During left ventricular contraction, the aorta is distended by blood flowing from the left ventricle, and kinetic energy from the ventricle is transformed into potential energy stored in the aortic wall. During recoil of the aortic wall, this potential energy is converted to kinetic energy, propelling aortic lumen blood into the periphery.

The volume of blood ejected into the aorta, the compliance of the aorta, and resistance to blood flow are responsible for the systolic pressures within the aorta. Resistance is mainly due to the tone of the peripheral vessels, although the inertia exerted by the column of blood during ventricular systole also plays a small part.

The aorta has thoracic and abdominal regions. The thoracic aorta is divided into the ascending, arch, and descending segments; the abdominal aorta is divided into suprarenal and infrarenal segments.

The ascending aorta is the anterior tubular portion of the thoracic aorta from the aortic root proximally to the innominate artery distally. The ascending aorta is 5 cm long and is made up of the aortic root and an upper tubular segment. The aortic root consists of the aortic valve, sinuses of Valsalva, and left and right coronary arteries. The aortic root extends from the aortic valve to the sinotubular junction. The aortic root supports the base of the aortic leaflets and allows the 3 sinuses of Valsalva to bulge outward, facilitating the full excursion of the leaflets in systole. The left and right coronary arteries arise from these sinuses.

The upper tubular segment of the ascending aorta starts at the sinotubular junction and ends at the beginning of the aortic arch. The ascending aorta lies slightly to the right of the midline, with its proximal portion in the pericardial cavity. Structures around the aorta include the pulmonary artery anteriorly; the left atrium, right pulmonary artery, and right mainstem bronchus posteriorly; and the right atrium and superior vena cava to the right.

The arch of the aorta curves upward between the ascending and descending aorta. The brachiocephalic arteries originate from the aortic arch. Arteries that arise from the aortic arch carry blood to the brain via the left common carotid, innominate, and left subclavian arteries. Initially, the aortic arch lies slightly left and in front of the trachea and ends posteriorly to the left of the trachea and esophagus. Inferior to the arch is the pulmonary artery bifurcation, the right pulmonary artery, and the left lung. The recurrent laryngeal nerve passes beneath the distal arch, and the phrenic and vagus nerves lie to the left. The junction between the aortic arch and the descending aorta is called the aortic isthmus. The isthmus is a common site for coarctations and trauma.

The descending aorta extends from distal to the left subclavian artery to the 12th intercostal space. Initially, the descending aorta lies in the posterior mediastinum to the left of the course of the vertebral column. It passes in front of the vertebral column in its descent and ends behind the esophagus before passing through the diaphragm at the level of the 12th thoracic vertebra. The abdominal aorta extends from the descending aorta at the level of the 12th thoracic vertebra to the level of bifurcation at the fourth lumbar vertebra. The splanchnic arteries branch from the abdominal aorta. The thoracoabdominal aorta is the combination of the descending thoracic and abdominal aorta.

With increasing age, the elasticity and distensibility of the aorta decline, thus inducing the increase in pulse pressure observed in elderly individuals. The progression of this process is exacerbated in patients with hypertension, coronary artery disease, or hypercholesterolemia. The loss of physiologic distensibility is observed anatomically by fragmentation of elastin and the resultant increase in collagen. This results in an increased collagen-to-elastin ratio. This, along with impairment in flow in the vasa vasorum, may be responsible for the age-related changes. These factors cumulatively lead to increased left ventricular systolic pressure and wall tension with associated increases in end-diastolic pressure and volume.

Cautions and relative contraindications to surgery include the following:

* Cerebrovascular accident
* Severe left ventricular dysfunction
* Coagulopathy
* Pregnancy
* Postmyocardial infarction ( <6 mo)
* Significant arrhythmias
* Advanced age
* Severe valvular disease


Loeffler Endocarditis


Loeffler endocarditis and endomyocardial fibrosis are restrictive cardiomyopathies, defined as diseases of the heart muscle that result in impaired ventricular filling with normal or decreased diastolic volume of either or both ventricles. Systolic function and wall thickness may remain normal, especially early in the disease, as reported by Richardson and associates.1 Both conditions are associated with eosinophilia.

The associations among eosinophilia, active carditis, and multiorgan involvement were first described by Loeffler in 1936.2 Pathologic specimens in Loeffler endocarditis show eosinophilic myocarditis, a tendency toward endomyocardial fibrosis and clinical manifestations of thromboembolism, and acute heart failure.

Eosinophilic states that may occur in association with Loeffler endocarditis include hypereosinophilic syndrome, eosinophilic leukemia, carcinoma, lymphoma, drug reactions or parasites, as reported in multiple case series.

Although eosinophilic endocardial disease has been well described, myocardial and vascular damage due to eosinophilic infiltration and degranulation is rarely diagnosed during life, as reported by Oakley et al and others.3 Herzog et al and Tonnesen et al have proposed that the reason for this situation may be the rapidly fatal evolution of most cases of eosinophilic arteritis and myocarditis.4,5 These conditions are usually diagnosed based on postmortem examination and nonspecificity of clinical manifestations, as reported by Kim et al, Isaka et al, and Seshadri et al.6,7,8

Pathophysiologically, the fibrotic stage of Loeffler endocarditis is very similar to the disease entity described as endomyocardial fibrosis, which is indolent in comparison to Loeffler endocarditis. The tropical form of endomyocardial fibrosis is associated with eosinophilia, a common finding in Loeffler endocarditis.

Endomyocardial damage in Loeffler endocarditis is well known and described in a study by Solley and associates.9 Myocardial involvement is less well known and has been considered a manifestation of an acute necrotic stage of eosinophilic endomyocardial disease, as reported by Olsen and colleagues.10 More recently, cases of isolated eosinophilic myocarditis have been reported without signs of endomyocardial involvement, with or without vasculitis.

Additionally, idiopathic eosinophilic endomyocarditis, in the absence of peripheral eosinophilia, has been reported by Priglinger et al.11

Morphologic abnormalities of eosinophils have been noted in patients with Loeffler endocarditis, suggesting that these eosinophils were mature or stimulated. The intracytoplasmic granular content of activated eosinophils is thought to be responsible for the toxic damage to the heart, as reported by Tai and associates.12 Spry et al reported eosinophilic degranulation of basic proteins causing myocardial damage in tissue cultures in vitro.13 Gliech et al reported a dose-dependent cytotoxic effect of the eosinophilic granular proteins, inhibiting multiple enzyme systems.14

The cationic eosinophilic proteins bind to the anionic endothelial protein, thrombomodulin. This complex impairs anticoagulant activities, leading to enhanced endocardial thrombus formation, as reported by Slungaard and colleagues.15

Toxins released by the eosinophils include eosinophil-derived neurotoxin, cationic protein, major basic protein, reactive oxygen species, and arachidonic acid derivatives. As described by Cunningham et al, these toxins may cause endothelial and myocyte damage, resulting in thrombosis, fibrosis, and infarction.16

The intensity and timing of the active carditis is related closely to the severity of the circulating eosinophilia. Some have suggested that, particularly in the tropics, patients who present with later fibrotic stages of endomyocardial disease may have had either transient earlier bouts of moderate eosinophilia with spontaneous resolution, or only moderate levels of eosinophilia leading to a low-grade endomyocarditis with gradual progressive fibrosis, as reported by Olsen et al.10

Molecular pathophysiology

Cools et al reported a landmark finding by treating patients with hypereosinophilic syndrome (HES) with imatinib, a tyrosine kinase inhibitor.17

* The gene defect is localized to an interstitial chromosomal deletion on chromosome band 4q12, resulting in fusion of the Fip1-like1 (FIP1L1) gene to the platelet-derived growth factor gene alpha (PDGFRA). The protein product of this gene is a tyrosine kinase enzyme that transforms the hematopoietic stem cells. This FIP1L1-PDGFRA fusion gene defect was identified in 9 of 16 patients treated with imatinib.
* This study also highlights the importance of reclassifying HES as a myeloproliferative disorder of a possible single clone based on genotyping, as the FIP1L1-PDGFRA gene rearrangement is a clonal abnormality.
* Treatment with imatinib caused rapid regression of eosinophilic proliferation and endomyocardiopathy in subsequent cases reported by Vandenberghe et al and Rotoli et al.18,19

The following list summarizes the initial clinical presentations of eosinophilic endomyocardial disease in relation to the predominant pathologic stage of the disease as reported by Alderman et al in the Textbook of Cardiovascular Medicine.20 Death is usually related to multiorgan dysfunction in the presence of congestive heart failure. (See Medscape's Heart Failure Resource Center.)

The initial clinical presentation and stages of eosinophilic endomyocardial disease are as follows:20

* Necrotic stage (early stage)
o Hypereosinophilia with systemic illness (20-30%)
+ Fever
+ Sweating
+ Chest pain (as described by Bestetti et al21 )
+ Lymphadenopathy
+ Splenomegaly
o Acute carditis (20-50%)
+ Anorexia
+ Weight loss
+ Cough
+ Pulmonary infiltrates
+ Skin and retinal lesion
+ Atrioventricular valve (AV) valve regurgitation
+ Biventricular failure
* Thrombotic stage
o Thrombotic emboli (10-20%)
+ Cerebral, splenic, renal, and coronary infarction
+ Splinter hemorrhages
* Fibrotic stage (late stage)
o Restrictive myopathy (10%)
+ AV valvular regurgitation
+ Right and left heart failure

The image shows dense fibrosis of ventricle in a postmortem dissected heart.

Myocardial as well as valvular involvement with L...
Myocardial as well as valvular involvement with Loffler endocarditis. This image shows dense fibrosis of ventricle in a postmortem dissected heart.


Myocardial as well as valvular involvement with L...

Myocardial as well as valvular involvement with Loffler endocarditis. This image shows dense fibrosis of ventricle in a postmortem dissected heart.

United States

The condition is rare and is seen mostly in immigrants from Africa, Asia, and South America.

Loeffler endocarditis is primarily confined to the rain forest (tropical and temperate) belts of Africa, Asia, and South America.

The literature reports a 35-50% 2-year mortality rate in patients with advanced myocardial fibrosis. Substantially better survival rates may be seen in less symptomatic patients who have milder forms of the disease. As noted, this rate may reflect underdiagnosis of clinically inapparent disease, as for other types of cardiomyopathy.

The condition has a predilection for African and African American populations, notably the Rwanda tribe in Uganda, and for people of low socioeconomic status. Whether this is due to genetic factors or the epidemiology of underlying environmental factors is not known.

Loeffler endocarditis has a predilection for males. However, endomyocardial fibrosis, which has similar clinical manifestations, is found equally frequently in both sexes.

The reported age range is 4-70 years. Loeffler endocarditis particularly affects young males, as does its close counterpart, endomyocardial fibrosis, which is more common in children and young adults.

Patients with Loeffler endocarditis may present with weight loss, fever, cough, rash, and symptoms related to congestive heart failure. Initial cardiac involvement has been reported in about 20-50% of cases; however, cardiac involvement rarely presents with chest pain, as reported by Bestetti et al.21

Signs of biventricular failure (eg, pedal edema, elevated jugulovenous pressure, pulmonary edema, third heart sound [S3] gallop) are commonly seen once congestive heart failure develops.

* Cardiomegaly may be present without overt signs of congestive heart failure.
* Murmur of mitral regurgitation may be present, as reported by multiple authors, including Weller et al.22
* Systemic embolism is frequent and may lead to neurologic and renal dysfunction.
* The Kussmaul sign may be present.
* S 3 gallop may be present, but rarely fourth heart sound (S4).
* Restrictive cardiomyopathy, such as Loeffler endocarditis, is sometimes difficult to differentiate from constrictive pericarditis. Physical signs in constrictive pericarditis that may help differentiate the 2 conditions include a nonpalpable apex (usually), presence of pericardial knock, and usually absent regurgitation murmurs.
* Published case reports highlight presentations with unusual ECG changes mimicking posterior myocardial infarction as described by Maruyoshi et al23 , acute myocardial infarction as described by Mor et al24 , and aortic valve regurgitation secondary to valve fibrosis and fibrotic vegetations on the aortic valve as described by Gudmundsson et al


Sudden Cardiac Death


Sudden cardiac death (SCD) is an unexpected death due to cardiac causes occurring in a short time period (generally within 1 h of symptom onset) in a person with known or unknown cardiac disease. Most cases of SCD are related to cardiac arrhythmias. Approximately half of all cardiac deaths can be classified as SCDs. SCD represents the first expression of cardiac disease in many individuals presenting with out-of-hospital cardiac arrest. This article explores the epidemiology, pathophysiology, diagnostic approach, and treatment of patients who experience SCD.


The most common electrophysiologic mechanisms leading to SCD are tachyarrhythmias such as ventricular fibrillation (VF) or ventricular tachycardia (VT). Interruption of tachyarrhythmias, using either an automatic external defibrillator (AED) or an implantable cardioverter defibrillator (ICD), has been shown to be an effective treatment for VF and VT.1 The implantable defibrillator has become the central therapeutic factor in the prevention and treatment of sudden cardiac death. Patients with tachyarrhythmias, especially VT, carry the best overall prognosis among patients with sudden cardiac arrest (SCA).

There are multiple factors at the organ (eg imbalance of autonomic tone), tissue (eg reentry, wave break, and action potential duration alternans), cellular (eg triggered activity, and automaticity) and subcellular (abnormal activation or deactivation of ion channels) level involved in generation of VT or VF in different conditions. An anatomical or a functional block in the course of impulse propagation may create a circuit with the wave front circling around it and resulting in VT. Other mechanisms such as wave break and collisions are involved in generating VF from VT. While at the tissue level the above-mentioned reentry and wave break mechanisms are the most important known mechanisms of VT and VF, at the cellular level increased excitation or decreased repolarization reserve of cardiomyocytes may result in ectopic activity (eg automaticity, triggered activity), contributing to VT and VF initiation.

At the subcellular level, altered intracellular Ca2+ currents, altered intracellular K+ currents (especially in ischemia), or mutations resulting in dysfunction of a sodium channel (Na+ channelopathy) can increase the likelihood of VT and VF.

Approximately 20-30% of patients with documented sudden death events have bradyarrhythmia or asystole at the time of initial contact. Oftentimes, it is difficult to determine with certainty the initiating event in a patient presenting with a bradyarrhythmia because asystole and pulseless electrical activity (PEA) may result from a sustained VT. Less commonly, an initial bradyarrhythmia producing myocardial ischemia may then provoke VT or VF.

Most cases of SCD occur in patients with structural abnormalities of the heart. Myocardial infarction (MI) and post-MI remodeling of the heart is the most common structural abnormality in patients with SCD. In patients who survive a myocardial infarction, the presence of premature ventricular contractions (PVCs), particularly complex forms such as multiform PVCs, short coupling intervals (R-on-T phenomenon), or VT (salvos of 3 or more ectopic beats), reflect an increased risk of sudden death. However suppression of the PVCs with antiarrhythmic drugs increases mortality, owing to the proarrhythmic risk of currently available medications.

Hypertrophic cardiomyopathy and dilated cardiomyopathy are associated with an increased risk of SCD. Various valvular diseases such as aortic stenosis are associated with increased risk of SCD. Acute illnesses, such as myocarditis, may provide both an initial and sustained risk of SCD due to inflammation and fibrosis of the myocardium.

Less commonly, SCD happens in patients who may not have apparent structural heart disease. These conditions are usually inherited arrhythmia syndromes.

Even though many patients have anatomic and functional cardiac substrates that predispose them to develop ventricular arrhythmias, only a small percentage develop SCD. Identifying the patients at risk for SCD remains a challenge. The strongest known predictor of SCD is significant left ventricular dysfunction of any cause. The interplay between the regional ischemia, LV dysfunction, and transient inciting events (eg, worsened ischemia, acidosis, hypoxemia, wall tension, drugs, metabolic disturbances) has been proposed as being the precipitator of sudden death (see Media file 1).

Interplay of various risk factors that can lead t...
Interplay of various risk factors that can lead to sudden cardiac death.


Interplay of various risk factors that can lead t...

Interplay of various risk factors that can lead to sudden cardiac death.

United States

SCD accounts for approximately 325,000 deaths per year in the United States; more deaths are attributable to SCD than to lung cancer, breast cancer, or AIDS. This represents an incidence of 0.1-0.2% per year in the adult population. SCD is often the first expression of CAD and is responsible for approximately 50% of deaths from CAD.

In several population-based studies, the incidence of out-of-hospital cardiac arrest has been noted as declining in the past 2 decades, but the proportion of sudden CAD deaths in the United States has not changed. A high incidence of SCD occurs among certain subgroups of high-risk patients (congestive heart failure with ejection fraction <30%, convalescent phase after myocardial infarction, patients who survived cardiac arrest). However, these populations are much smaller than patients with minimal or even inapparent coronary artery disease. Consequently, in the overall population, most SCD occurs in lower risk patients. The time dependence of risk for SCD has been noted in several studies, with an increased number of events in the first 6-24 months after surviving a major cardiovascular event.

The frequency of SCD in Western industrialized nations is similar to that in the United States. The incidence of SCD in other countries varies as a reflection of the prevalence of coronary artery disease or other high-frequency cardiomyopathies in those populations. The trend toward increasing SCD events in developing nations of the world is thought to reflect a change in dietary and lifestyle habits in these nations. It has been estimated that SCD claims more than 7,000,000 lives per year worldwide.2


Of more than 300,000 deaths attributed to SCD in the United States each year, a large portion (as many as 40%) are unwitnessed. For most people who experience SCD, their survival depends on the presence of individuals who are competent in performing basic life support, the rapid arrival of personnel and apparatus for defibrillation and advanced life support, and transfer to a hospital. Even under ideal circumstances, only an estimated 20% of patients who have out-of-hospital cardiac arrest survive to hospital discharge. In a study of out-of-hospital cardiac arrest survival in New York City, only 1.4% of patients survived to hospital discharge. Other studies in suburban and rural areas have indicated higher rates of survival (as high as 35%). Placement of automatic external defibrillators throughout communities and training people to use them has the potential to markedly improve outcomes from SCD.

* Upon emergency department (ED) presentation, the most important determinants of survival include (1) an unsupported systolic blood pressure (SBP) greater than 90 mm Hg, (2) a time from loss of consciousness to return of spontaneous circulation (ROSC) of less than 25 minutes, and (3) some degree of neurological responsiveness.
* A major adverse outcome from a SCD event is anoxic encephalopathy, which occurs in 30-80% of cases.


Most studies demonstrate inconclusive data with regard to racial differences as they relate to the incidence of sudden death. Some studies suggest that a greater proportion of coronary deaths were "sudden" in blacks compared to whites. In a report by Gillum et al on SCD from 1980-1985, the percentage of coronary artery disease deaths occurring out of the hospital and in EDs was found to be higher in blacks than in whites (see Media file 2).3

Cardiac death, sudden. Plots of mortality rates (...
Cardiac death, sudden. Plots of mortality rates (deaths per 1000 persons) for ischemic heart disease occurring out of the hospital or in the emergency department (top) and occurring in the hospital (bottom) by age, sex, and race in 40 states during 1985.


Cardiac death, sudden. Plots of mortality rates (...

Cardiac death, sudden. Plots of mortality rates (deaths per 1000 persons) for ischemic heart disease occurring out of the hospital or in the emergency department (top) and occurring in the hospital (bottom) by age, sex, and race in 40 states during 1985.


Men have a higher incidence of SCD than women, with a ratio of 3:1. This ratio generally reflects the higher incidence of obstructive coronary artery disease in men. Recent evidence suggests that a major sex difference may exist in the mechanism of myocardial infarction. Basic and observational data point to the fact that men tend to have coronary plaque rupture, while women tend to have plaque erosion. Whether this biologic difference accounts for the male predominance of SCD is unclear.

The incidence of SCD parallels the incidence of coronary artery disease, with the peak of SCD occurring in people aged 45-75 years. The incidence of SCD increases with age in men, women, whites, and nonwhites as the prevalence of coronary artery disease increases with age. However, the proportion of deaths that are sudden from coronary artery disease decreases with age. In the Framingham study, the proportion of coronary artery disease deaths that were sudden was 62% in men aged 45-54 years, but this percentage fell to 58% in men aged 55-64 years and to 42% in men aged 65-74 years.4 According to Kuller et al, 31% of deaths are sudden in people aged 20-29 years.5


Obtaining a thorough history from the patient, family members, or other witnesses is necessary to obtain insight into the events surrounding the sudden death. Patients at risk for SCD may have prodromes of chest pain, fatigue, palpitations, and other nonspecific complaints. History and associated symptoms, to some degree depend on the underlying etiology of SCD. For example, SCD in an elderly patient with significant coronary artery disease may be associated with preceding chest pain due to a myocardial infarction, while SCD in a young patient may be associated with history of prior syncopal episodes and/or a family history of syncope and SCD and due to inherited arrhythmia syndromes. As many as 45% of persons who have SCD were seen by a physician within 4 weeks before death, although as many as 75% of these complaints were not related to the cardiovascular system. A prior history of LV impairment (ejection fraction <30-35%) is the most potent common risk factor for sudden death.

Risk factors that relate to coronary artery disease and subsequent myocardial infarction and ischemic cardiomyopathy also are important and include a family history of premature coronary artery disease, smoking, dyslipidemia, hypertension, diabetes, obesity, and a sedentary lifestyle. Specific considerations include the following:

* Coronary artery disease
o Previous cardiac arrest
o Syncope
o Prior myocardial infarction, especially within 6 months
o Ejection fraction less than 30-35%
o History of frequent ventricular ectopy (more than 10 PVCs per h or nonsustained VT)
* Dilated cardiomyopathy
o Previous cardiac arrest
o Syncope
o Ejection fraction less than 30-35%
o Use of inotropic medications
* Hypertrophic cardiomyopathy
o Previous cardiac arrest
o Syncope
o Family history of SCD
o Symptoms of heart failure
o Drop in SBP or ventricular ectopy upon stress testing
o Palpitations
o Most are asymptomatic
* Valvular disease
o Valve replacement within 6 months
o Syncope
o History of frequent ventricular ectopy
o Symptoms associated with severe uncorrected aortic stenosis or mitral stenosis
* Long QT syndrome
o Family history of long QT and SCD
o Medications that prolong the QT interval
o Bilateral deafness
* Wolff-Parkinson-White (WPW) syndrome (with atrial fibrillation or atrial flutter with extremely rapid ventricular rates): With extremely rapid conduction over an accessory pathway, degeneration to VF can occur.
* Brugada syndrome, arrhythmogenic right ventricular (RV) cardiomyopathy/dysplasia, and others


The physical examination may reveal evidence of underlying myocardial disease or may be entirely normal, depending on the underlying cause. Initial evaluation studies show that patients who survive to ED presentation can be stratified by a cardiac arrest score, which has excellent diagnostic value. The cardiac arrest score, developed by Thompson and McCullough, can be used for patients with witnessed out-of-hospital cardiac arrest and is defined by the following criteria6,7 :

* Clinical characteristic points
o ED SBP greater than 90 mm Hg = 1 point
o ED SBP less than 90 mm Hg = 0 points
o Time to ROSC less than 25 minutes = 1 point
o Time to ROSC more than 25 minutes = 0 points
o Neurologically responsive = 1 point
o Comatose = 0 point
o Maximum score = 3 points
* Patients with a score of 3 points can be expected to have an 89% chance of neurologic recovery and an 82% chance of survival to discharge (see Media file 3).

Cardiac death, sudden. Figure a shows neurologic ...
Cardiac death, sudden. Figure a shows neurologic outcome stratified by initial cardiac arrest score. Neurologic recovery is defined as discharged home and able to care for self. Figure b shows overall survival stratified by initial cardiac arrest score.


Cardiac death, sudden. Figure a shows neurologic ...

Cardiac death, sudden. Figure a shows neurologic outcome stratified by initial cardiac arrest score. Neurologic recovery is defined as discharged home and able to care for self. Figure b shows overall survival stratified by initial cardiac arrest score.
* McCullough indicates that even in the setting of ST elevation and early invasive management with primary angioplasty and intraaortic balloon pump insertion, patients with low cardiac scores are unlikely to survive.8
* Severe anoxic encephalopathy in patients with scores of 0, 1, or 2 mitigates conservative management with empiric supportive and medical therapy. Given the very poor actuarial survival rates for these patients, invasive management with catheterization and electrophysiology studies (EPS) is rarely justified.


Ischemic heart disease

* Cardiac arrest due to ventricular arrhythmias may be due to post-MI remodeling of the heart with scar formation and interstitial fibrosis (intramyocardial collagen deposition) or to acute MI/ischemia. A chronic infarct scar can serve as the focus for reentrant ventricular tachyarrhythmias. This can occur shortly after the infarct or years later. Interestingly, post-MI remodeling and ischemic cardiomyopathy may be associated with increased interstitial fibrosis even in noninfarcted areas of the heart.9 Interstitial fibrosis can provide anatomical block similar to a scar. Fibroblasts and myocytes shown to be coupled through gap junctions and fibroblasts can reduce repolarization reserve of myocytes. In addition to post-MI remodeling, many other structural heart diseases associated with SCD (eg, dilated cardiomyopathy, hypertrophic cardiomyopathy, and aortic stenosis) are also associated with increased myocardial fibrosis.10,11,12
* Many studies support the relationship of symptomatic and asymptomatic ischemia as a factor for risk of SCD. Patients resuscitated from out-of-hospital cardiac arrest represent a group of patients with increased recurrence of cardiac arrest and have been shown to express an increased incidence of silent ST-segment depression. Experiments inducing myocardial ischemia in animal models have a strong relationship with the development of VF. However, in patients with prior myocardial infarction and scarring, ventricular arrhythmias, especially VT, do not require an acute ischemic trigger.
* In postmortem studies of people who have died from SCD, extensive atherosclerosis is a common pathologic finding. In survivors of cardiac arrest, coronary heart disease with vessels showing greater than 75% stenosis is observed in 40-86% of patients, depending on the age and sex of the population studied. Autopsy studies show similar results; in one study of 169 hearts, approximately 61% of patients died of SCD, and more than 75% stenosis in 3 or 4 vessels and similar severe lesions were present in at least 2 vessels in another 15% of cases. No single coronary artery lesion is associated with an increased risk for SCD. Despite these findings, only approximately 20% of SCD-related autopsies have shown evidence of a recent MI. A greater proportion of autopsies (40-70%) show evidence of a healed MI. Many of these hearts also reveal evidence of plaque fissuring, hemorrhage, and thrombosis.
* The Cardiac Surgery Study (CASS) showed that improving or restoring blood flow to an ischemic myocardium decreased the risk of SCD, especially in patients with 3-vessel disease and heart failure, when compared with medical treatment over a 5-year period.
* The efficacy of beta-blocking agents, such as propranolol, in decreasing sudden death mortality, especially when administered to patients who had MI with VF, VT, and high-frequency PVCs, may be due in part to the ability of beta-blockers to decrease ischemia, but they are also effective in patients with nonischemic cardiomyopathy for reduction of SCD. Beta-blockers also increase the VF threshold in ischemic animals and decrease the rate of ventricular ectopy in patients who had MI.
* Reperfusion of ischemic myocardium with thrombolysis or direct percutaneous coronary intervention can induce transient electrical instability by several different mechanisms.
* Coronary artery spasm is a condition that exposes the myocardium to both ischemia and reperfusion insults. It is occasionally associated with VT, VF, and SCD. Since some of the episodes of coronary vasospasm may be silent, this disease should be considered in a patient with unexplained SCA.13 The exact mechanism of ventricular arrhythmia in coronary vasospasm is not known, but factors associated with both ischemia and reperfusion may contribute in induction of arrhythmia.
* Nonatherosclerotic coronary artery abnormalities, including congenital lesions, coronary artery embolism, coronary arteritis, and mechanical abnormalities of the coronary artery, have been associated with an increased incidence of sudden death.

Nonischemic cardiomyopathies

Patients with nonischemic cardiomyopathies represent the second largest group of patients who experience SCD in the United States. Nonischemic myopathies, for the purpose of this article, can be divided into the categories dilated and hypertrophic.

* Dilated cardiomyopathy
o Dilated cardiomyopathy can result from prior ischemia and myocardial infarction or from nonischemic causes. Nonischemic dilated cardiomyopathy (DCM) is becoming increasingly more common, with an incidence of approximately 7.5 cases per 100,000 persons each year. Of cases of SCD, 10% are estimated to be attributable to DCM. The prognosis is very poor for these patients, with a 1-year mortality rate of 10-50%, depending on the New York Heart Association functional class; approximately 30-50% of these deaths are SCD.
o The causes of DCM are uncertain; viral, autoimmune, genetic, and environmental (alcohol) origins are implicated. The predominant mechanism of death appears to be ventricular tachyarrhythmia, although bradyarrhythmia and electromechanical dissociation also have been observed, especially in patients with advanced LV dysfunction. Extensive fibrosis of the subendocardium, leading to dilated ventricles and subsequent generation of reentrant tachyarrhythmias, is a proposed factor in mechanism of sudden death. Multiple factors have been shown to contribute to increased risk for SCD in this population. The most important hemodynamic predictor is an increase in end-diastolic pressure and subsequent wall tension. Other important factors are increased sympathetic tone, neurohumoral activation, and electrolyte abnormalities.
o Many drugs used in the treatment of heart failure, such as antiarrhythmics, inotropic agents, and diuretics, have direct or indirect (eg, through electrolyte abnormalities) proarrhythmic properties, which may provoke arrhythmias in some cases. Potassium-sparing diuretics may be helpful in decreasing SCD.
o Nonsustained ventricular tachycardia (NSVT) is common in patients with dilated cardiomyopathy and approximately 80% of persons with DCM have abnormalities on Holter monitoring. Although NSVT may be a marker, it has not been shown to be a reliable predictor of SCD in these patients. Recent studies have shown possibility of increased mortality following suppression of NSVT by antiarrhythmic medications due to proarrhythmic properties of these medications and involvement of several other factors in generation of VT and VF. Given the possibility of sustained VT being the underlying cause, a history of syncope should be aggressively pursued. Unexplained syncope, especially in patients with class 3 or 4 heart failure, has been shown to be a predictor of SCD in most patients with cardiomyopathy
* Hypertrophic cardiomyopathy
o Hypertrophic cardiomyopathy (HCM) is an autosomal-dominant, incompletely penetrant genetic disorder resulting from a mutation in one of the many (>45) genes encoding proteins of the cardiac muscle sarcomere. Among the genetic abnormalities described, mutations in the genes coding for the beta-myosin heavy chains, and cardiac troponin T make up most cases. Other mutations may include alpha-myosin heavy chain MYH6), cardiac troponin C (TNNC1), alpha-tropomyosin (TPM1), myosin binding protein-C (MYBPC3), cardiac troponin (TNNI3), essential and regulatory light-chain genes (MYL 3 and MYL 2, respectively), cardiac alpha-actin gene (ACTC), and titin (TTN). The incidence of SCD in this population is 2-4% per year in adults and 4-6% per year in children and adolescents. HCM is the most common cause of SCD in people younger than 30 years.
o The vast majority of young people who die of HCM are previously asymptomatic. The patients may experience SCD while at rest or with mild exertional activity; however, in a significant portion of these patients, the SCD event occurs after vigorous exertion. HCM is the single greatest cause of SCD in young athletes and, hence, is the major entity for which to screen during the physical examination of an athlete.
o The mechanism of SCD in HCM is not entirely understood. Initially, it was thought to be due to obstruction of the outflow tract because of catecholamine stimulation. However, later studies suggested that individuals with nonobstructive HCM are at high risk for SCD as well, primarily related to VT or VF. The mechanism of arrhythmia in this setting is not clear, and hypertrophy may be a part of cardiac remodeling in these patients that provides the substrate for lethal arrhythmia.
o Rapid or polymorphic symptomatic NSVT may have better predictive value compared with asymptomatic and monomorphic NSVT. Other clinical markers that may have predictive value for SCD in patients with HCM are young age at onset, thickness of the septum, and family history of SCD.
* Arrhythmogenic right ventricular cardiomyopathy
o Arrhythmogenic RV cardiomyopathy is characterized by replacement of the RV wall with fibrofatty tissue. Involvement of the interventricular septum and left ventricle is associated with poorer outcomes.
o About 30-50% of cases occur as a phenotypically apparent familial disorder. Several genetic defects, including mutations in the desmoplakin domain locus on chromosome 6 and the ryanodine receptor locus on chromosome 1 (although this has been debated), have been correlated with SCD. Again, interstitial fibrosis plays an important role in ventricular arrhythmia in this condition. Autosomal dominant inheritance is common, but autosomal recessive transmission has been reported for select mutations. The autosomal recessive form, Naxos disease (named after the Greek Island), has been reported in a geographically isolated area mainly in Mediterranean countries and is usually associated with wooly hair and palmoplantar keratoderma or similar skin disorder. This disorder is associated with mutation in the gene for plakoglobin, a protein involved in cellular adhesion, found on chromosome 17p.
o Arrhythmogenic RV dysplasia affects men more often than women. The annual incidence rate of SCD in this population is approximately 2%. Patients may present with signs and symptoms of RV hypertrophy and dilation, often with sustained monomorphic or polymorphic VT of a left bundle-branch block morphology with an axis usually between negative 90-100°
o Atrial arrhythmias may be present in as many as 25% of patients. Syncope and sudden death often are associated with exercise. In many patients, sudden death is the first manifestation of the disease. Clinicians should be alerted to the epsilon wave finding on ECG studies (see Media file 4). The epsilon wave can be present in as many as 23% of patients after the first VT event. The percentage of patients with the epsilon wave finding on ECG increases to 27% and 34% at 5 and 10 years, respectively, after the first VT event.

Cardiac death, sudden. Epsilon wave in a patient ...
Cardiac death, sudden. Epsilon wave in a patient with arrhythmogenic right ventricular dysplasia.


Cardiac death, sudden. Epsilon wave in a patient ...

Cardiac death, sudden. Epsilon wave in a patient with arrhythmogenic right ventricular dysplasia.
o Uhl anomaly is a condition in which the RV wall is extremely thin secondary to apposition of endocardial and epicardial layers.

Valvular disease

* Prior to the advent of surgical therapy for valvular heart disease, SCD was fairly common in patients with progressive aortic stenosis.
o Most aortic stenosis deaths were sudden. In a study by Chizner et al of 42 patients who had isolated aortic stenosis and did not undergo valve replacement, as many as 56% of deaths were sudden at 5 years of follow-up. Of these 42 patients, 32 were symptomatic and 10 were asymptomatic.14
o The mechanism of sudden death is unclear, and both malignant ventricular arrhythmia and bradyarrhythmia have been documented.
o The incidence of SCD has decreased significantly with advent of aortic valve replacement. However, it still accounts for the second most common cause of death postoperatively in this population and especially in those with prosthetic and heterograft aortic valve replacement. The incidence of SCD after aortic valve surgery is highest in the first 3 weeks after the procedure and then plateaus at 6 months of follow-up.

Other valvular lesions

The risk of SCD is much lower in other valvular diseases compared with aortic stenosis.

* Aortic insufficiency usually presents with signs of heart failure and progressive LV dilatation. As part of this process, reentrant or automatic ventricular foci may develop and ultimately lead to a symptomatic ventricular arrhythmia. After valve replacement, LV wall tension can be expected to reduce and the risk of arrhythmia can be expected to decrease.
* Mitral stenosis is becoming increasingly uncommon in the United States because of widespread use of antibiotics in primary streptococcal infections. SCD due to mitral stenosis is very rare.
* The incidence of SCD is low in patients with mitral valve prolapse (MVP). MVP has a 5-7% incidence in the general population. In clinically significant MVP, the risk of SCD seems to rise along with total mortality. Kligfield et al estimated that the incidence of sudden death varies with the presence of symptoms and the severity of mitral regurgitation. Ventricular tachyarrhythmias are the most frequent arrhythmia in patients with SCD. Risk factors for SCD to consider in these patients include a family history of SCD, echocardiographic evidence of a redundant mitral valve, repolarization abnormalities, and lengthening of the corrected QT interval (>420 ms in women and >450 ms in men).

Congenital heart disease

In the pediatric and adolescent age groups, SCD occurs with an incidence of 1.3-8.5 cases per 100,000 patients annually, accounting for approximately 5% of all deaths in this group. The causes of SCD are much more diverse in children than adults. In reviewing 13 studies involving 61 children and adolescents with SCD, Driscoll found 50% of cases were due to HCM; 25% were due to anomalous origin of the left coronary artery; and the remaining patients had aortic stenosis, cystic medial necrosis, and sinus node artery obstruction. The following is a classification of SCD in the pediatric population.

* In patients with known, previously recognized (including repaired) congenital heart disease, abnormalities associated with SCD include the following:
o Tetralogy of Fallot
o Transposition of the great arteries
o Fontan operation
o Aortic stenosis
o Marfan syndrome
o Mitral valve prolapse
o Hypoplastic left heart syndrome
o Eisenmenger syndrome
o Congenital heart block
o Ebstein anomaly
* In patients with known, previously recognized (including repaired) heart disease, acquired causes of SCD include the following:
o Kawasaki syndrome
o DCM or myocarditis
* In patients with previously unrecognized heart disease who have structural heart disease, causes of SCD include the following:
o Congenital coronary artery abnormalities
o Arrhythmogenic RV cardiomyopathy
* In patients with previously unrecognized heart disease who do not have structural heart disease, causes of SCD include the following:
o Long QT syndrome
o WPW syndrome
o Primary ventricular tachycardia and ventricular fibrillation
o Primary pulmonary hypertension
o Commotio cordis - Traumatic blow to the chest wall (eg, from a hockey puck or baseball) causing VT/VF and SCD in the absence of significant identifiable trauma
* The predominant mechanism is ventricular arrhythmias. In tetralogy of Fallot after postoperative correction of the anomaly, as many as 10% of these patients have VT and the incidence of sudden death is 2-3%. In the Fontan procedure, ie, to correct a physiologic single ventricle, even atrial arrhythmias can cause severe hemodynamic compromise and arrhythmic death. Patients who develop secondary pulmonary hypertension (Eisenmenger syndrome), despite attempted correction of the anatomic defects, have a very poor prognosis. The terminal event may be bradycardia or VT progressing to VF.

Primary electrophysiologic abnormalities

This generally represents a group of abnormalities in which patients have no apparent structural heart disease but have a primary electrophysiologic abnormality that predisposes them to VT or VF. Some imaging techniques have detected abnormal sympathetic neural function in these patients. An ECG study can provide clues to the diagnosis; consider a familial component to these conditions. Normal early repolarization may be associated with increased SCD, though this often represents a benign finding.15

* Long QT syndrome
o Idiopathic long QT syndrome, in which patients have a prolonged QT with a propensity to develop malignant ventricular arrhythmias, is a rare familial disorder.
o Two inheritance patterns of congenital long QT syndrome have been described. The Jervell-Lange-Nielsen syndrome, associated with congenital deafness, has an autosomal-recessive pattern of inheritance. The Romano-Ward syndrome is not associated with deafness and has an autosomal dominant pattern of inheritance with variable penetration. This syndrome accounts for 90% of long QT syndrome cases. More than 200 mutations in the 10 or more genes related to long QT syndrome have been found. Among the most common are mutations of SCN5A on chromosome 3, the HERG gene on chromosome 7, and the KVLTQT1 gene on chromosome 11.
o Alteration in the function of a myocellular channel protein that regulates the potassium flux during electrical repolarization is thought to be causative, though in some subsets of long QT syndrome, such as those with mutations in SCN5A (long QT3), Na channels are primarily impaired. A relationship with sympathetic nervous system imbalance also appears to exist. The prolongation that occurs makes these patients susceptible to develop a specific form of VT called torsade de pointes.
o The clinical course of patients with long QT syndrome is quite variable, with some patients remaining asymptomatic while others develop torsade de pointes with syncope and sudden death. Symptoms and SCD are more common among homozygous individuals (those with two copies of the mutant allele), compared with heterozygous individuals (who have a single mutant allele). The risk of SCD is impacted by environmental factors such as hypokalemia, medications and the presence of sinus pauses. SCD in these patients also has been associated with emotional extremes, auditory auras or stimulation, and vigorous physical activity. Symptoms usually begin in childhood or adolescence.
o The probability that a specific patient has congenital long QT syndrome is divided to low, intermediate, and high probability based on the following criteria: (1) ECG criteria including long QT, torsade de pointes, notched T wave, T wave alternans, bradycardia for age; (2) clinical criteria including syncope with or without stress, deafness; and (3) family history of long QT syndrome or SCD.
o When measuring QTc, selecting rhythm strips that have minimal variability of RR intervals and a stable heart rate is important.
o Treatment for long QT syndrome includes beta-blockers and often pacemaker or ICD implantation. Beta-blockers decrease the overall mortality in patients with long QT syndrome. However, they do not eliminate the risk of syncope, cardiac arrest, and SCD completely. They are not effective in patients with mutation in Na channel genes (long QT3). Torsade de pointes in patients with long QT syndrome is associated with bradycardia and pauses. Therefore, a pacemaker can prevent torsade de pointes in these patients by preventing bradycardia. ICD therapy may be indicated in patients with recurrent symptoms despite treatment with beta-blockers.
* Acquired long QT syndrome
o A number of antiarrhythmics (especially class Ia and class III) and other medications, electrolyte abnormalities, cerebrovascular diseases, and altered nutritional states are known to cause QT prolongation and put patients at risk for torsade de pointes. This usually occurs when QT prolongation is associated with a slow heart rate and hypokalemia.
o The QT interval is prolonged in as many as 32% of patients with intracranial hemorrhage (especially in subarachnoid hemorrhages). Lesions in the hypothalamus are thought to lead to this phenomenon.
o Reports of sudden death due to ventricular arrhythmia in patients with hypocalcemia, hypothyroidism, nutritional deficiencies associated with modified starvation diets, and in patients who are obese and on severe weight-loss programs have been reported.
o Class Ia antiarrhythmic drugs that cause acquired long QT syndrome include quinidine, disopyramide, and procainamide. Class III antiarrhythmic drugs that cause acquired long QT syndrome include sotalol, N -acetyl procainamide, bretylium, amiodarone, and ibutilide.
o Other drugs that cause acquired long QT syndrome include bepridil, probucol, tricyclic and tetracyclic antidepressants, phenothiazines, Haldol, antihistamines (eg, terfenadine, astemizole), antibiotics (eg, erythromycin, sulfamethoxazole/trimethoprim), chemotherapeutics (eg, pentamidine, anthracycline), serotonin antagonists (eg, ketanserin, zimeldine), and organophosphorus insecticides.
o Electrolyte abnormalities that cause acquired long QT syndrome include hypokalemia, hypomagnesemia, and hypocalcemia.
o Altered nutritional states and cerebrovascular disease that cause acquired long QT syndrome include intracranial and subarachnoid hemorrhages, stroke, and intracranial trauma.
o Hypothyroidism and altered autonomic status (eg, diabetic neuropathy) can cause acquired long QT syndrome.
o Hypothermia can cause acquired QT prolongation. The ECG will typically also demonstrate an Osborn wave, a distinct bulging of the J point at the beginning of the ST segment. This ECG finding resolves upon warming.
* Short QT syndrome
o The short QT syndrome is a newly recognized syndrome, first time described in 2000, which can lead to lethal arrhythmias and SCD. Three mutations in potassium channels have been described that lead to gain of function in potassium channels and shortening of action potential and decreased QT interval.
o To diagnose short QT syndrome, the QTc should be less than 330 msec and tall and peaked T waves should be present. Clinical manifestations are variable from no symptoms, to palpitations due to atrial fibrillation, syncope due to VT, and SCD. VF is easily inducible at electrophysiology study in these patients, and SCD can happen at any age.
o Although antiarrhythmic medications, such as sotalol, ibutilide, and procainamide, have been proposed as a therapy (to prolong the QT), data to support this approach are insufficient at present. ICD placement may be considered to prevent VT and SCD, although T-wave oversensing, resulting in inappropriate ICD discharges, has been problematic.
* Wolff-Parkinson-White syndrome
o WPW syndrome is a recognized but rare cause of sudden death. The existence of an atrioventricular accessory pathway in this syndrome results in ventricular preexcitation, which appears with short PR interval, wide QRS complex, and delta wave on ECG. The refractory period in the anterograde direction of accessory pathway determines the ventricular rate in the setting of atrial fibrillation and WPW. Most patients with WPW syndrome and SCD develop atrial fibrillation with a rapid ventricular response over the accessory pathway, which induces VF (see Media file 5). In a study by Klein et al of 31 patients with VF and WPW syndrome, a history of atrial fibrillation or reciprocating tachycardia was an important predisposing factor. The presence of multiple accessory pathways, posteroseptal accessory pathways, and a preexcited R-R interval of less than 220 ms during atrial fibrillation are associated with higher risk for SCD.

Cardiac death, sudden. Ventricular fibrillation a...
Cardiac death, sudden. Ventricular fibrillation appeared during rapid atrial fibrillation in a patient with Wolff-Parkinson-White syndrome.


Cardiac death, sudden. Ventricular fibrillation a...

Cardiac death, sudden. Ventricular fibrillation appeared during rapid atrial fibrillation in a patient with Wolff-Parkinson-White syndrome.
o Symptomatic patients should be treated by antiarrhythmic medications (eg, procainamide), catheter ablation of the accessory pathway, or electrical cardioversion depending on the severity and frequency of symptoms. Asymptomatic patients may be observed without treatment.
o Medications such as digoxin, adenosine, and verapamil that block the AV node are contraindicated in patients with WPW and atrial fibrillation because they may accelerate conduction through the accessory pathway, potentially causing VF and SCD.
* Brugada syndrome
o In 1992, Brugada and Brugada described a syndrome of a specific ECG pattern of right bundle-branch block and ST-segment elevation in leads V1 through V3 without any structural abnormality of the heart, that was associated with sudden death.
o In 25-30% of these patients, a mutation in SCN5A on chromosome 3 is detected. This mutation results in a sodium channelopathy. The most common clinical presentation is syncope, and this mutation is most common in young males and in Asians. It is associated with VT, VF, and SCD.
o Three ECG types of Brugada pattern are described. Only type 1,- which consists of a coving ST elevation in V1 to V3 with downsloping ST segment and inverted T waves, pseudo RBBB pattern with no reciprocal ST changes and normal QTc, is specific enough to be diagnostic for Brugada syndrome when it is associated with symptoms. The other two ECG patterns of Brugada are not diagnostic, but they merit further evaluation.
o The Brugada ECG pattern can be dynamic and not found on an index ECG. When clinical suspicion is high, a challenge test with procainamide or some other Na channel blocker may be diagnostic by reproducing the type 1 ECG pattern.
* Although antiarrhythmic medications, catheter ablation and pacemaker therapies all have potential, in young and symptomatic patients, an ICD should be implanted to prevent VF and SCD. ICD therapy is the only proven treatment to date. Whether ICD placement is indicated in older or asymptomatic patients is controversial at present.
o Catecholaminergic polymorphic ventricular tachycardia
+ Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a syndrome that presents with polymorphic VT, syncope, or SCD, and in about half of these patients, a mutation in one of two different genes have been detected.
+ The polymorphic VT is characteristically induced by emotional or physical stress (eg, exercise stress test). The medical therapy of choice is administration of beta-blockers, and ICD may be indicated. New data may support the use of flecainide in the treatment of this disease.16
* Primary ventricular fibrillation occurs in a structurally normal heart due to idiopathic etiology.
o An estimated 3-9% of cases of VT and VF occur in the absence of myocardial ischemia. As many as 1% of patients with out-of-hospital cardiac arrest have idiopathic VF with no structural heart disease. As many as 15% of patients younger than 40 years who experience VF have no underlying structural heart disease. Viskin and Behassan noted that of 54 patients with idiopathic VF, 11 patients had histologic abnormalities on endomyocardial biopsy.
o SCD is often the first presentation of VF in patients at risk but who have had no preceding symptoms. In those patients who survive, VF may recur in as many as one third of patients.
o The options for medical therapy include beta-blockers and class 1A antiarrhythmic drugs, but limited data are available regarding their efficacy. The mainstay of treatment is preventing VF by ICD placement. Mapping and radiofrequency ablation of the triggering foci is an option for those patients who experience frequent episodes of VF following ICD placement.
* Right ventricular outflow tract ventricular tachycardia
o Right ventricular outflow tract (RVOT) tachycardia is the most common form of idiopathic VT, comprising 70-80% of all idiopathic VTs. RVOT tachycardia is a very rare cause of SCD. It also has been referred to as exercise-induced VT, adenosine-sensitive VT, and repetitive monomorphic VT.
o RVOT tachycardia occurs in patients without structural heart disease and arises from the RV outflow region. Current data suggest that triggered activity is the underlying mechanism of RVOT tachycardia. RVOT tachycardia is believed to be receptor-mediated because exogenous and endogenous adenosine can terminate this process. Maneuvers that increase endogenous acetylcholine also have been demonstrated to antagonize this process.
o Symptoms typical of RVOT tachycardia include palpitations and presyncope or syncope, often occurring during or after exercise or emotional stress. VT also can occur at rest. The ECG during VT displays a left bundle-branch block/inferior axis morphology.
o Treatment is based on frequency and severity of symptoms. The first line of therapy is a beta-blocker or calcium channel blocker. Patients with symptoms not relieved by medical therapy are best treated with radiofrequency catheter ablation. Successful ablation is reported in 83-100% of cases.

Other causes of sudden death

Two major causes of sudden cardiopulmonary death deserve mention.

* Pulmonary embolism is a frequent cause of sudden death in people at risk. Risk factors include previous personal or family history of deep venous thromboembolism, malignancy, hypercoagulable states, and recent mechanical trauma such as hip or knee surgery.
* Aortic dissection or aneurysmal rupture is the other major cause of out-of-hospital nonarrhythmic cardiovascular death. Predisposing factors for aortic dissection include genetic deficiencies of collagen such as Marfan syndrome, Ehlers-Danlos syndrome, and aortic cystic medial necrosis.


Jual Rumah Kontrakan 2 Pintu

Jual Rumah Kontrakan 2 Pintu
Jl. Gang Biyuk, Bambu Kuning Raya. Akses Strategis = Jalan Raya Pramuka Narogong, Rawalumbu Bekasi, Bebas Banjir, Tanpa Perantara = Ibu Anni 021-95-08-20-42 *.(Klik Gambar untuk Keterangan Lanjut)




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