Alcoholic Cardiomyopathy

Overview

The focus of this review is on the effects of alcohol on the myocardium and its role as a cause of heart failure due to dilated cardiomyopathy (DC). For nearly 150 years, alcohol consumption has been associated with a variety of cardiovascular diseases. Observations during the second half of the 19th century described cardiac enlargement seen at autopsy and heart failure symptoms in persons who had consumed excessive amounts of alcohol.

During the first half of the 20th century, the concept of beriberi heart disease (ie, thiamine deficiency) was present throughout the medical literature, and the idea that alcohol had any direct effect on the myocardium was doubted. Epidemics of heart failure in persons who had consumed beer contaminated with arsenic in the 1900s and cobalt in the 1960s also obscured the observation that alcohol could exhibit a direct toxic effect. In the 1950s, evidence began to emerge that supported the idea of a direct toxic myocardial effect of alcohol, and research during the last 25 years has been particularly productive in characterizing the disease entity of alcoholic cardiomyopathy (AC).

Ultimately, AC is a clinical diagnosis made in a patient presenting with a constellation of findings that includes a history of excessive alcohol intake, possible physical signs of alcohol abuse (eg, parotid disease, telangiectasia or spider angiomata, mental status changes, cirrhosis), heart failure, and supportive evidence consistent with DC. Hypertension due to alcohol may be a confounding comorbidity in that it may contribute to LV dysfunction; therefore, LV dysfunction due to hypertension must be differentiated from pure AC.

Proposed mechanisms of injury in AC include the following:

Inhibition of protein synthesisInhibition of oxidative phosphorylationFatty acid ester accumulationFree radical damageInhibition of calcium-myofilament interactionInflammatory and immunologic factorsReceptor abnormalitiesDisruption of cell membrane structureCoronary vasospasmSynergy with concomitant conditionsActivation of the renin-angiotensin system[1]

Alcohol use has also been shown to have numerous effects on the cardiovascular system other than heart failure. It has been associated with arrhythmia (eg, atrial fibrillation, atrial flutter, other supraventricular arrhythmia, premature ventricular contractions), hypertension, stroke, and sudden death. In addition, the literature reports alcohol withdrawal being associated with takotsubo, or stress-induced, cardiomyopathy. On the other hand, numerous studies have demonstrated that light to moderate alcohol consumption (ie, 1-2 drinks per d or 3-9 drinks per wk) decreases the risk of cardiac events such as myocardial infarction.

Patient education

For patient education information, see the Mental Health Center, as well as Alcoholism, Alcohol Intoxication, Drug Dependence and Abuse, and Substance Abuse.

NextCardiac Effects of Alcohol

Long-term alcohol use has been implicated as the etiology of left ventricular (LV) dysfunction in as many as one third of cases of DC. The mechanism by which alcohol causes cardiac damage remains unclear. Over many years, several theories have arisen based on clinical and scientific data obtained in human and animal studies.

The original theories regarding the mechanism focused on nutritional deficiencies (eg, thiamine deficiency), secondary exposures (eg, tobacco, cobalt, arsenic), and other comorbidities (eg, hypertension). However, although these mechanisms may play a role in selected patients, most evidence in the literature indicates that the effects of alcohol on the myocardium are independent of these factors and that the effect is a direct toxic result of ethanol or its metabolites.

Some studies have suggested that a genetic vulnerability exists to the myocardial effects of alcohol consumption. Individuals with certain mitochondrial deoxyribonucleic acid (DNA) mutations and angiotensin-converting enzyme (ACE) genotypes (DD genotype) may be particularly susceptible to the damaging effects of alcohol. Exactly how these genetic variables create this higher risk is not known.

In addition, alcohol has been shown to have a negative effect on net protein synthesis. Many studies have shown this result, and it remains a topic of ongoing investigation and speculation. The exact manner in which alcohol produces this effect is not known, but the effect is consistent, is observed throughout the heart, and may be exaggerated under stressful conditions.

To identify the causative agent of alcoholic cardiomyopathy (AC), investigators administered ethanol to rats pretreated with inhibitors of ethanol metabolism. Use of ethanol alone or ethanol with an alcohol dehydrogenase inhibitor resulted in a 25% decrease in protein synthesis. When the rats were given an inhibitor of acetaldehyde dehydrogenase to increase levels of the ethanol metabolite acetaldehyde, an 80% decrease in protein synthesis occurred. Based on these data, acute ethanol-induced injury appears to be mediated by ethanol and acetaldehyde; the latter may play a more important role.

Acetaldehyde is a potent oxidant and, as such, increases oxidative stress, leading to the formation of oxygen radicals, with subsequent endothelial and tissue dysfunction. Acetaldehyde may also result in impairment of mitochondrial phosphorylation. Mitochondria play an essential role in cellular metabolism, and disruption of their function can have profound effects on the entire cell. The myocyte mitochondria in the hearts of persons exposed to alcohol are clearly abnormal in structure, and many believe that this may be an important factor in the development of AC.

A study in a rat model using an alcohol dehydrogenase transgene that results in elevated levels of acetaldehyde demonstrated a change in calcium metabolism at the intracellular level and a decrease in peak shortening and shortening velocity. This was interpreted by the authors as suggesting that acetaldehyde plays a key role in the cardiac dysfunction seen after alcohol intake. Others have suggested that an acute decrease in mitochondrial glutathione content may play a role in mitochondrial damage and implicate oxidative stress as a contributor in this process.

The formation of fatty acid ethyl esters during the metabolism of alcohol and specific genetic defects in fatty acid ethyl ester synthase (which metabolizes these esters and may predispose individuals to these toxic effects) have been proposed to result in further impairment of mitochondrial phosphorylation. Acetaldehyde has also been associated with coronary vasospasm and the release of troponin T in the acute setting. The latter effect can be blocked by the administration of propranolol, implicating beta-adrenergic stimulation as an effect of acetaldehyde.

Other proposed mechanisms of injury include a direct inhibition of calcium-myofilament interaction, free radical induced lipopigment accumulation within the myocyte and inhibition of protein synthesis, an inflammatory or myocarditislike response (possibly secondary to antibodies formed against protein-acetaldehyde adducts), reduced receptor expression, abnormal membrane structure, disruption of zinc homeostasis, and an increase in myocardial superoxide dismutase activity (resulting in an antioxidant imbalance).[2]

PreviousNextQuantity of Alcohol Intake in Cardiac Disease

Excessive intake of alcohol may result in increased systemic blood pressure in a dose-response relationship, and this may contribute to chronic myocardial dysfunction. Patients who consume more than 2 drinks per day have a 1.5- to 2-fold increase in hypertension compared with persons who do not drink alcohol, and this effect is most prominent when the daily intake of alcohol exceeds 5 drinks. Because hypertension may directly contribute to left ventricular (LV) dysfunction, this may be a confounding comorbidity in persons who abuse alcohol, and it should be differentiated from pure forms of AC.

In 1989, Urbano-Marquez et al reported on 48 men with alcohol abuse with a mean daily intake of 243 g of alcohol and showed (1) an inverse relationship between total lifetime intake and ejection fraction and fractional shortening and (2) a direct relationship between total lifetime intake and LV mass. In persons who consumed 70 g of ethanol (or the equivalent of 7 oz of whiskey, 20 oz of wine, or 72 oz of beer [ie, six 12-oz cans]) per day for 20 years, 36% had an abnormal ejection fraction. Age and nutritional status appeared to play little or no role.[3]

In a 1986 study, Richardson et al concluded that continuous, rather than episodic, drinking was a major risk factor for the development of heart failure and that this effect was unrelated to the hypertensive effect of alcohol. In the study, the authors evaluated 38 patients with nonischemic DC. Of these persons, 18 were classified as heavy drinkers (ie, 80 g/d or a lifetime dose of 250 kg), and 20 were classified as abstinent or light drinkers. Those classified as heavy drinkers all were men who predominantly drank beer.[4]

Other studies and reviews have also quoted quantities similar to those mentioned above, and the type of beverage consumed appeared to be irrelevant.

Binge drinking induces a systemic inflammatory reaction, which may lead to alcohol-induced myocardial inflammation. One study indicated that patients who repeatedly expose themselves to excessive amounts of alcohol may demonstrate evidence on magnetic resonance imaging (MRI) scans of alcohol-induced myocardial inflammation but not show deterioration in indices of LV performance. The study did not provide evidence of an absolute acute risk of cardiac events involved with binge drinking, and the clinical significance of the findings requires further investigation.[5]

PreviousNextEpidemiologySex-related demographics

Currently available data indicate that certain aspects of alcoholic cardiomyopathy (AC) are affected by the patient's sex. Several authors have reported that although AC is a disease that affects males more often than females (due to a higher rate of alcohol abuse in men), females may be more sensitive to alcohol's cardiotoxic effects.

In 1997, Fernandez-Sola and colleagues evaluated 10 women and 26 men who were alcohol abusers and reported a similar prevalence of cardiomyopathy in the males and females, despite a lower total lifetime alcohol dose in the women.[6]

In 1995, Urbano-Marquez described similar results in a study of 50 women and 100 men who abused alcohol. The authors reported a lifetime dose of alcohol in the female group that was 60% of that in the male group, but they found an equal incidence of cardiomyopathy and myopathy in the males and females.[7]

Based on their work with a rat model, Jankala and colleagues suggested a link between lower levels of p53 mRNA expression and female susceptibility to the development of AC.[8]

Age-related demographics

Alcoholic cardiomyopathy is a disease that primarily affects persons of at least middle age and is observed less commonly in those younger than age 40 years, although preclinical cardiac abnormalities have been demonstrated in persons engaging in chronic alcohol abuse. This is believed to be due primarily to the fact that alcohol must be consumed excessively for at least 10 years to have a clinically relevant effect on the myocardium.

PreviousNextPrognosis

The natural history of patients with alcoholic cardiomyopathy (AC) depends greatly on each patient's ability to cease alcohol consumption completely. Multiple case reports and small retrospective and prospective studies have clearly documented marked improvement in or, in some patients, normalization of cardiac function with abstinence. The following reports and studies provide impressive data on the utility of abstinence and the confirmation of alcohol consumption as a cause of DC.

Nakanishi et al identified 11 patients with AC and reported significant improvement in 8 of them after they abstained from alcohol use. In addition, a marked worsening was seen in the 3 patients who continued to abuse alcohol, including death from heart failure in 2 patients.[9]

A 12-month observational study of 20 patients with AC noted smaller cavity diameters, better clinical evaluation findings, and fewer hospitalizations in the 10 patients who abstained from alcohol use.

Guillo and colleagues evaluated 14 patients with AC over a 3-year period with serial examinations, electrocardiograms (ECGs), stress tests, echocardiograms, and MUGA scans. Of the 3 patients who continued to drink, 1 was lost to follow-up and 2 died. One patient underwent heart transplantation within the 3 years of follow-up observation, and 1 patient died from tamponade after an endomyocardial biopsy. Nine of the original 14 patients completed the 36-month follow-up period, 6 patients had marked improvement in symptoms and increased ejection fractions. The other 3 patients had no change in ejection fraction, one patient cut back alcohol consumption, and another patient resumed use after a period of abstinence.[10]

A 1- and 4-year follow-up study of 55 men with alcoholism showed that abstinence and controlled drinking of up to 60 g/day (4 drinks) resulted in comparable improvement in LV ejection fraction. Ten patients who continued to drink higher amounts of alcohol all died during the follow-up period.

Demakis and colleagues found that, overall, the 2 factors that were associated with a better prognosis in AC were abstinence and a shorter duration of symptoms before the initiation of therapy. In their study, perhaps the largest evaluation of the natural history of AC, the investigators prospectively followed 57 patients with AC and divided them into 3 groups: 15 patients who improved clinically, 12 patients who remained stable, and 30 patients whose conditions deteriorated. Of the 39 patients who continued to drink, only 4 patients improved. Eleven of the 18 patients who abstained improved; however, the condition of 3 patients who abstained continued to deteriorate.[11]

In 1996, Prazak et al conducted a retrospective study comparing 23 patients with AC to 52 patients with idiopathic DC and found that the 1-, 5-, and 10-year survival rates for AC were 100%, 81%, and 81%, respectively, compared with 89%, 48%, and 30%, respectively, for idiopathic DC. When transplant-free survival was compared between the 2 groups, the difference was more impressive, with 10-year survival rates of 81% and 20% for the AC and idiopathic DC patients, respectively. The 2 groups had similar ejection fractions, New York Heart Association class symptoms, and overall LV volume. The sole endpoint was all-cause mortality.[12]

In contrast to the Prazak study, a 1993 study by Redfield et al showed no difference in mortality between patients with AC and those with idiopathic DC.[13] Prazak et al speculated that the outcomes in the reports may have differed because the patients in their study observed more complete abstinence and underwent aggressive medical therapy.[12]

Alcoholic cardiomyopathy and cirrhosis

For many years, people who abused alcohol and had cirrhosis were believed to be spared from the cardiotoxic effects of alcohol; conversely, those with cardiomyopathy were believed to be spared from cirrhosis. However, research has shown that this almost certainly is not the case. In a study, Estruch et al found that persons who abused alcohol and had been hospitalized solely for cardiomyopathy had a higher incidence of cirrhosis than did alcohol abusers who did not have heart disease.[14]

PreviousNextPatient History

Similar to the pathologic findings, the symptoms of alcoholic cardiomyopathy (AC) are essentially the same as those associated with other forms of DC. Dyspnea, orthopnea, and paroxysmal nocturnal dyspnea are the hallmark complaints, but chest discomfort, fatigue, palpitations, dizziness, syncope, anorexia, and many others are not uncommon.

The onset of symptoms is usually insidious, but acute decompensations are also observed, especially in patients with asymptomatic LV dysfunction who develop atrial fibrillation or other tachyarrhythmia and, because of this, are unable to increase their cardiac output.

Ask any patient presenting with new heart failure of unclear etiology about their alcohol history, with attention to daily, maximal, and lifetime intake and the duration of that intake. Several important studies have clearly shown a dose-dependent effect.

PreviousNextPhysical Examination

Physical examination findings in AC are not unique compared with findings in DC from other causes. Elevated systemic blood pressure may reflect excessive intake of alcohol, but not alcoholic cardiomyopathy per se.

Frequently, a relative decrease occurs in systolic blood pressure because of reduced cardiac output and increased diastolic blood pressure due to peripheral vasoconstriction, resulting in a decrease in the pulse pressure.

Cardiac percussion and palpation reveal evidence of an enlarged heart with a laterally displaced and diffuse point of maximal impulse. Auscultation can help to reveal the apical murmur of mitral regurgitation and the lower parasternal murmur of tricuspid regurgitation secondary to papillary muscle displacement and dysfunction. Third and fourth heart sounds can be heard, and they signify systolic and diastolic dysfunction. Pulmonary rales signify pulmonary congestion secondary to elevated left atrial and LV end-diastolic pressures. Jugular venous distention, peripheral edema, and hepatomegaly are evidence of elevated right heart pressures and right ventricular dysfunction.

Other findings may include cool extremities with decreased pulses and generalized cachexia, muscle atrophy, and weakness due to chronic heart failure and/or the direct effect of chronic alcohol consumption.

PreviousNextLaboratory Studies

Results from serum chemistry evaluations have not been shown to be useful for distinguishing patients with alcoholic cardiomyopathy (AC) from those with other forms of DC. Results from evaluations of mean cell volume, aspartate aminotransferase levels, alanine aminotransferase levels, lactate dehydrogenase (LDH) levels, and gamma-glutamyltransferase levels have been shown to be similar in persons with AC to those in persons with other forms of DC. However, results from tissue assays have been shown to be potentially helpful in distinguishing AC from other forms of DC.

Richardson et al showed an elevation of creatine kinase, LDH, malic dehydrogenase, and alpha-hydroxybutyric dehydrogenase levels in endomyocardial biopsy specimens taken from 38 patients with DC.

PreviousNextImaging Studies

Chest radiographs usually show evidence of cardiac enlargement, pulmonary congestion, and pleural effusions.

Results from resting and stress nuclear imaging techniques (eg, stress testing with thallium and sestamibi imaging, multiple gated acquisition [MUGA] scanning, positron emission tomography [PET scanning]) may be useful for evaluating cardiac size and function and for screening for coronary disease.

Echocardiography

Echocardiography is perhaps the most useful initial diagnostic tool in the evaluation of patients with heart failure. Because of the ease and speed of the test and its noninvasive nature, it is the study of choice in the initial and follow-up evaluation of most forms of cardiomyopathy. In addition, it provides information not only on overall heart size and function, but on valvular structure and function, wall motion and thickness, and pericardial disease.

Echocardiographic findings in persons with AC, which are similar to those in persons with idiopathic DC, are as follows:

4-chamber dilatationGlobally decreased ventricular functionMitral and tricuspid regurgitationPulmonary hypertensionEvidence of diastolic dysfunction - These changes can be seen even in the absence of systolic dysfunction but seem to be more prevalent in patients with coexisting systolic dysfunction; the progression of diastolic dysfunction in asymptomatic individuals may be related to the duration of alcoholism Intracardiac thrombi (atrial or ventricular)LV hypertrophyPreviousNextElectrocardiography

Electrocardiographic findings are frequently abnormal, and these findings may be the only indication of heart disease in asymptomatic patients.

Palpitations, dizziness, and syncope are common complaints and are frequently caused by arrhythmias (eg, atrial fibrillation, flutter) and premature contractions. In the setting of acute alcohol use or intoxication, this is called holiday heart syndrome, because the incidence is increased following weekends and during holiday seasons.

Other supraventricular tachyarrhythmias and sudden death have also been associated with alcohol use and alcoholic cardiomyopathy (AC), with the latter being most likely secondary to the development of ventricular fibrillation. Conduction disturbances, such as degrees of atrioventricular block, left or right bundle-branch block, and hemiblocks, are also observed.

Criteria associated with LV hypertrophy with a repolarization abnormality, prolonged repolarization (ie, QT interval), nonspecific ST- and T-wave changes, and Q waves have also been described.

PreviousNextCardiac Catheterization

In patients with DC, if additional questions remain after a history is obtained and noninvasive testing is performed, cardiac catheterization may be used to help exclude other etiologies of heart failure.

Although the most common cause of heart failure is coronary artery disease, ischemic cardiomyopathy is unlikely in the absence of a clear history of prior ischemic events or angina and in the absence of Q waves on the ECG strip. In most patients, exercise or pharmacologic stress testing with echocardiographic or nuclear imaging is an appropriate screening test for heart failure due to coronary artery disease.

In addition to the assessment of the status of the coronary arteries, cardiac catheterization may help obtain useful information regarding cardiac output, the degree of aortic or mitral valvular disease, and cardiac hemodynamics and filling pressures. Importantly however, remember that much of this information can be derived or inferred from the results of noninvasive testing.

In persons with AC, common findings after catheterization include nonobstructive coronary disease; elevated LV end-diastolic pressure, wedge pressure, pulmonary artery pressure, and right heart pressure; increased LV size with decreased overall function; and mild or moderate mitral regurgitation. Regional wall motion abnormalities are not uncommon, but they are usually less prominent than those observed in persons with ischemic heart disease.

PreviousNextHistologic Findings

The pathologic and histologic findings of alcoholic cardiomyopathy (AC) are essentially indistinguishable from those of other forms of DC. Findings from gross examination include an enlarged heart with 4-chamber dilatation and overall increased cardiac mass. Histologically, light microscopy reveals interstitial fibrosis (a finding that has been shown to be prevented by zinc supplementation in the mouse model), myocyte necrosis with hypertrophy of other myocytes, and evidence of inflammation. Electron microscopy reveals mitochondrial enlargement and disorganization, dilatation of the sarcoplasmic reticulum, fat and glycogen deposition, and dilatation of the intercalating discs.

Although the qualitative properties of AC and other forms of DC may be similar, quantitative differences may exist.

Comparing 20 patients who had AC with 10 patients with DC, Teragaki and colleagues reported less myocyte hypertrophy and fibrosis in patients with AC, found a greater improvement of cardiac size with treatment or abstinence in the AC group, and noted that the cardiac index was higher in patients with AC who had less fibrosis.[15, 16]

In the 1989 study by Urbano-Marquez et al, a comparison of symptomatic to asymptomatic patients revealed more extensive fibrosis in patients with symptoms.[3] Other investigators have looked at immunohistologic markers and have suggested that the presence of these markers might suggest an inflammatory process such as myocarditis and that their absence may point more toward AC or an idiopathic etiology.

PreviousNextAlcohol Abstention and Pharmacologic Therapies

The mainstay of therapy for alcoholic cardiomyopathy (AC) is to treat the underlying cause, ie, to have the patient exercise complete and perpetual abstinence from all alcohol consumption. The efficacy of abstinence has been shown in persons with early disease (eg, prior to the onset of severe myocardial fibrosis) and in individuals with more advanced disease (see Prognosis).

Medical therapy for AC is identical to conventional therapy for other forms of heart failure. This includes treatment with an ACE inhibitor and with digoxin (for patients with symptomatic LV dysfunction), as well as the symptomatic use of diuretics. Newer therapies, such as beta blockers in stable patients without decompensated heart failure, are also used.

Electrolyte abnormalities, including hypokalemia, hypomagnesemia, and hypophosphatemia, should be corrected promptly because of the risk of arrhythmia and sudden death.

Although anticoagulation may be of benefit to patients with profound LV dysfunction and atrial fibrillation, the risks must be weighed heavily in this patient population.

Thiamine (200 mg once daily), multivitamins, vitamin B-12, folate, and mineral supplementation are beneficial for patients with AC because of the significant prevalence of concomitant nutritional or electrolyte deficiencies in these patients. Animal studies have suggested a benefit from vitamins B-1 and B-12, speculated to be due to protective effects against apoptosis and protein damage.

A summary of the treatment for AC is as follows:

Abstention from alcoholVasodilators - ACE inhibitors, angiotensin receptor blockers (the work of Cheng and colleagues in 2006 suggested that these may prevent the development of AC[17] ), nitrates, hydralazineDigoxinDiureticsBeta blockersAnticoagulation (possibly)Intravenous inotropic agentsCardiac transplantationPrevious, Alcoholic Cardiomyopathy

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Dilated Cardiomyopathy

Practice Essentials

Dilated cardiomyopathy is a progressive disease of heart muscle that is characterized by ventricular chamber enlargement and contractile dysfunction with normal left ventricular (LV) wall thickness. The right ventricle may also be dilated and dysfunctional. Dilated cardiomyopathy is the third most common cause of heart failure and the most frequent reason for heart transplantation.

Essential update: A prognostic marker for nonischemic dilated cardiomyopathy

Left atrial volume indexed to body surface area (LAVi) assessed by cardiovascular MRI independently predicted transplant-free survival and heart failure outcomes in a recent study of 483 patients with non-ischemic dilated cardiomyopathy. Patients with an LAVi above the optimal cut-off value of 72 mL/m2 had a threefold elevated risk of death or transplantation; furthermore, LAVi provided incremental prognostic value for the prediction of transplant-free survival.[1]

Signs and Symptoms

Symptoms are a good indicator of the severity of dilated cardiomyopathy and may include the following:

FatigueDyspnea on exertion, shortness of breathOrthopnea, paroxysmal nocturnal dyspneaIncreasing edema, weight, or abdominal girth

On physical examination, look for signs of heart failure and volume overload. Assess vital signs with specific attention to the following:

TachypneaTachycardiaHypertension

Other pertinent findings include the following (the level of cardiac compensation or decompensation determines which signs are present):

Signs of hypoxia (eg, cyanosis, clubbing)Jugular venous distension (JVD)Pulmonary edema (crackles and/or wheezes)S3 gallopEnlarged liverPeripheral edema

Look for the following on examination of the neck:

Jugular venous distention (as an estimate of central venous pressure)Hepatojugular refluxa waveLarge cv wave (observed with tricuspid regurgitation)Goiter

Findings on examination of the heart may include the following:

Cardiomegaly (broad and displaced point of maximal impulse, right ventricular heave)Murmurs (with appropriate maneuvers)S2 at the base (paradoxical splitting, prominent P2), S3, and S4TachycardiaIrregularly irregular rhythmGallops

See Clinical Presentation for more detail.

Diagnosis

The workup in a patient with suspected cardiomyopathy may include the following:

Complete blood countMetabolic panelThyroid function testsCardiac biomarkersB-type natriuretic peptide assayChest radiographyEchocardiographyCardiac magnetic resonance imaging (MRI)Electrocardiography (ECG)

In many cases of cardiomyopathy, endomyocardial biopsy is class II (uncertain efficacy and may be controversial) or class III (generally not indicated). Class II indications for endomyocardial biopsy include the following:

Recent onset of rapidly deteriorating cardiac functionPatients receiving chemotherapy with doxorubicinPatients with systemic diseases with possible cardiac involvement (eg, hemochromatosis, sarcoidosis, amyloidosis, Löffler endocarditis, endomyocardial fibroelastosis)

See Workup for more detail.

Management

Treatment of dilated cardiomyopathy is essentially the same as treatment of chronic heart failure (CHF). Some therapeutic interventions treat symptoms, whereas others treat factors that affect survival.

Drug classes used include the following:

Angiotensin-converting enzyme (ACE) inhibitorsAngiotensin II receptor blockers (ARBs)Beta-blockersAldosterone antagonistsCardiac glycosidesDiureticsVasodilatorsAntiarrhythmicsHuman B-type natriuretic peptideInotropic agents

Anticoagulants may be used in selected patients.

Surgical options for patients with disease refractory to medical therapy include the following:

Left ventricular assist devicesCardiac resynchronization therapy (biventricular pacing)Automatic implantable cardioverter-defibrillatorsVentricular restoration surgeryHeart transplantation

See Treatment and Medication for more detail.

NextBackground

Dilated cardiomyopathy is a progressive disease of heart muscle that is characterized by ventricular chamber enlargement and contractile dysfunction with normal left ventricular (LV) wall thickness. The right ventricle may also be dilated and dysfunctional. Dilated cardiomyopathy is the third most common cause of heart failure and the most frequent reason for heart transplantation.

Dilated cardiomyopathy is 1 of the 3 traditional classes of cardiomyopathy, along with hypertrophic and restrictive cardiomyopathy. However, the classification of cardiomyopathies continues to evolve, based on the rapid evolution of molecular genetics as well as the introduction of recently described diseases.

Multiple causes of dilated cardiomyopathy exist, one or more of which may be responsible for an individual case of the disease (see Etiology). All alter the normal muscular function of the myocardium, which prompts varying degrees of physiologic compensation for that malfunction.

The degree and time course of malfunction are variable and do not always coincide with a linear expression of symptoms. Persons with cardiomyopathy may have asymptomatic LV systolic dysfunction, LV diastolic dysfunction, or both. When compensatory mechanisms can no longer maintain cardiac output at normal LV filling pressures, the disease process is expressed with symptoms that collectively compose the disease state known as chronic heart failure (CHF).

Continuing ventricular enlargement and dysfunction generally leads to progressive heart failure with further decline in LV contractile function. Sequelae include ventricular and supraventricular arrhythmias, conduction system abnormalities, thromboembolism, and sudden death or heart failure–related death.

Cardiomyopathy is a complex disease process that can affect the heart of a person of any age, but it is especially important as a cause of morbidity and mortality among the world's aging population. It is the most common diagnosis in persons receiving supplemental medical financial assistance via the US Medicare program.

Nonpharmacologic interventions are the basis of heart failure therapy. Instruction on a sodium diet restricted to 2 g/day is very important and can often eliminate the need for diuretics or permit the use of reduced dosages. Fluid restriction is complementary to a low-sodium diet. Patients should be enrolled in cardiac rehabilitation involving aerobic exercise.

For patient education information, see the Heart Center, as well as Congestive Heart Failure.

PreviousNextPathophysiology

Dilated cardiomyopathy is characterized by ventricular chamber enlargement and systolic dysfunction with greater LV cavity size with little or no wall hypertrophy. Hypertrophy is judged as the ratio of LV mass to cavity size; this ratio is decreased in persons with dilated cardiomyopathies.

The enlargement of the remaining heart chambers is primarily due to LV failure, but it may be secondary to the primary cardiomyopathic process. Dilated cardiomyopathies are associated with both systolic and diastolic dysfunction. The decrease in systolic function is by far the primary abnormality. This leads to an increase in the end-diastolic and end-systolic volumes.

Progressive dilation can lead to significant mitral and tricuspid regurgitation, which may further diminish the cardiac output and increase end-systolic volumes and ventricular wall stress. In turn, this leads to further dilation and myocardial dysfunction.

Early compensation for systolic dysfunction and decreased cardiac output is accomplished by increasing the stroke volume, the heart rate, or both (cardiac output = stroke volume ´ heart rate), which is also accompanied by an increase in peripheral vascular tone. The increase in peripheral tone helps maintain appropriate blood pressure. Also observed is an increased tissue oxygen extraction rate with a shift in the hemoglobin dissociation curve.

The basis for compensation of low cardiac output is explained by the Frank-Starling Law, which states that myocardial force at end-diastole compared with end-systole increases as muscle length increases, thereby generating a greater amount of force as the muscle is stretched. Overstretching, however, leads to failure of the myocardial contractile unit.

These compensatory mechanisms are blunted in persons with dilated cardiomyopathies, as compared with persons with normal LV systolic function. Additionally, these compensatory mechanisms lead to further myocardial injury, dysfunction, and geometric remodeling (concentric or eccentric).

Neurohormonal activation

Decreased cardiac output with resultant reductions in organ perfusion results in neurohormonal activation, including stimulation of the adrenergic nervous system and the renin-angiotensin-aldosterone system (RAAS). Additional factors important to compensatory neurohormonal activation include the release of arginine vasopressin and the secretion of natriuretic peptides. Although these responses are initially compensatory, they ultimately lead to further disease progression.

Alterations in the adrenergic nervous system induce significant increases in circulating levels of dopamine and, especially, norepinephrine. By increasing sympathetic tone and decreasing parasympathetic activity, an increase in cardiac performance (beta-adrenergic receptors) and peripheral tone (alpha-adrenergic receptors) is attempted.

Unfortunately, long-term exposure to high levels of catecholamines leads to down-regulation of receptors in the myocardium and blunting of this response. The response to exercise in reference to circulating catecholamines is also blunted. Theoretically, the increased catecholamine levels observed in cardiomyopathies due to compensation may in themselves be cardiotoxic and lead to further dysfunction. In addition, stimulation of the alpha-adrenergic receptors, which leads to increased peripheral vascular tone, increases the myocardial workload, which can further decrease cardiac output. Circulating norepinephrine levels have been inversely correlated with survival.

Activation of the RAAS is a critical aspect of neurohormonal alterations in persons with CHF. Angiotensin II potentiates the effects of norepinephrine by increasing systemic vascular resistance. It also increases the secretion of aldosterone, which facilitates sodium and water retention and may contribute to myocardial fibrosis.

The release of arginine vasopressin from the hypothalamus is controlled by both osmotic (hyponatremia) and nonosmotic stimuli (eg, diuresis, hypotension, angiotensin II). Arginine vasopressin may potentiate the peripheral vascular constriction because of the aforementioned mechanisms. Its actions in the kidneys reduce free-water clearance.

Natriuretic peptide levels are elevated in individuals with dilated cardiomyopathy. Natriuretic peptides in the human body include atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide. ANP is primarily released by the atria (mostly the right atrium). Right atrial stretch is an important stimulus for its release. The effects of ANP include vasodilation, possible attenuation of cell growth, diuresis, and inhibition of aldosterone. Although BNP was initially identified in brain tissue (hence its name), it is secreted from cardiac ventricles in response to volume or pressure overload. As a result, BNP levels are elevated in patients with CHF. BNP causes vasodilation and natriuresis.

Counterregulatory responses to neurohormonal activation involve increased release of prostaglandins and bradykinins. These do not significantly counteract the previously described compensatory mechanisms.

The body's compensatory mechanisms for a failing heart are evidently shortsighted. Compensation for decreased cardiac output cannot be sustained without inducing further decompensation. The rationale for the most successful medical treatment modalities for cardiomyopathies is therefore based on altering these neurohormonal responses.

Circulating cytokines as mediators of myocardial injury

Tissue necrosis factor-alpha (TNF-alpha) is involved in all forms of cardiac injury. In cardiomyopathies, TNF-alpha has been implicated in the progressive worsening of ventricular function, but the complete mechanism of its actions is poorly understood. Progressive deterioration of LV function and cell death (TNF plays a role in apoptosis) are implicated as some of the mechanisms of TNF-alpha. It also directly depresses myocardial function in a synergistic manner with other interleukins.

Elevated levels of several interleukins have been found in patients with left ventricular dysfunction. Interleukin (IL)–1b has been shown to depress myocardial function. One theory is that elevated levels of IL-2R in patients with class IV CHF suggest that T-lymphocytes play a role in advanced stages of heart failure.

IL-6 stimulates hepatic production of C-reactive protein, which serves as a marker of inflammation. IL-6 has also been implicated in the development of myocyte hypertrophy, and elevated levels have been found in patients with CHF. IL-6 has been found to correlate with hemodynamic measures in persons with left ventricular dysfunction.

PreviousNextEtiology

Dilated cardiomyopathy has many causes, including inherited disease, infections, and toxins. Finding a specific cause for an individual case may be difficult, especially in patients with multiple risk factors.

Causes of dilated cardiomyopathy include the following:

GeneticsSecondary to other cardiovascular disease: ischemia, hypertension, valvular disease, tachycardia inducedInfectious: viral, rickettsial, bacterial, fungal, metazoal, protozoalProbable infectious: Whipple disease, Lyme diseaseMetabolic: endocrine diseases (eg, hyperthyroidism, hypothyroidism, acromegaly, myxedema, hypoparathyroidism, hyperparathyroidism), diabetes mellitus, electrolyte imbalance (eg, potassium, phosphate, magnesium) Nutritional: thiamine deficiency (beriberi), protein deficiency, starvation, carnitine deficiencyToxic: drugs, poisons, foods, anesthetic gases, heavy metals, ethanolCollagen vascular diseaseInfiltrative: hemochromatosis, amyloidosis, glycogen storage diseaseGranulomatous (sarcoidosis)Physical agents: extreme temperatures, ionizing radiation, electric shock, nonpenetrating thoracic injuryNeuromuscular disorders: muscular dystrophy (limb-girdle [Erb dystrophy], Duchenne dystrophy, fascioscapulohumeral [Landouzy-Dejerine dystrophy]), Friedreich disease, myotonic dystrophy Primary cardiac tumor (myxoma)SenilePeripartumImmunologic: postvaccination, serum sickness, transplant rejection

In many cases of dilated cardiomyopathy, the cause remains unexplained. However, some idiopathic cases may result from failure to identify known causes such as infections or toxins. The idiopathic category should continue to diminish as more information explaining pathophysiologic mechanisms, specifically genetic-environmental interactions, becomes available.

Toxins are a significant cause. Almost a third of cases may result from severe ethanol abuse.

Viral myocarditis

Viral myocarditis is an important entity within the category of infectious cardiomyopathy. Viruses have been implicated in cardiomyopathies as early as the 1950s, when coxsackievirus B was isolated from the myocardium of a newborn baby with a fatal infection. Advances in genetic analysis, such as polymerase chain reaction testing, have aided in the discovery of several viruses that are believed to have roles in viral cardiomyopathies.

Viral infections and viruses associated with myocardial disease may be caused by the following:

Coxsackievirus (A and B)Influenza virus (A and B)AdenovirusEchovirusRabiesHepatitisYellow feverLymphocytic choriomeningitisEpidemic hemorrhagic feverChikungunya feverDengue feverCytomegalovirusEpstein-Barr virusRubeolaRubellaMumpsRespiratory syncytial virusVaricella-zoster virusHuman immunodeficiency virus

Viral myocarditis can produce variable degrees of illness, ranging from focal disease to diffuse pancarditis involving myocardium, pericardium, and valve structures. Viral myocarditis is usually a self-limited, acute-to-subacute disease of the heart muscle. Symptoms are similar to those of CHF and often are subclinical. Many patients experience a flulike prodrome.

Confirming the diagnosis can be difficult because symptoms of heart failure can occur several months after the initial infection. Patients with viral myocarditis (median age, 42 years) are generally healthy and have no systemic disease.

Acute viral myocarditis can mimic acute myocardial infarction, with patients sometimes presenting in the emergency department with chest pain; nonspecific electrocardiographic (ECG) changes; and abnormal, often highly elevated serum markers such as troponin, creatine kinase, and creatine kinase-MB.

The diagnosis of viral myocarditis is mainly indicated by a compatible history and the absence of other potential etiologies, particularly if it can be confirmed with acute or convalescent sera. An ECG demonstrates varying degrees of ST-T wave changes reflecting myocarditis and, sometimes, varying degrees of conduction disturbances. Echocardiography is a crucial aid in classifying this disease process, which manifests mostly as a dilated type of cardiomyopathy.

Myocarditis is almost always a clinically presumed diagnosis because it is not associated with any pathognomonic sign or specific, acute diagnostic laboratory test result. In the past, percutaneous transvenous right ventricular endomyocardial biopsy has been used, but the Myocarditis Treatment Trial revealed no advantage for immunosuppressive therapy in biopsy-proven myocarditis, so biopsy is not routinely performed in most cases.

If a patient is thought to have viral myocarditis, the initial diagnostic strategies should be to evaluate cardiac troponin I or T levels and to perform antimyosin scintigraphy. Positive troponin I or T findings in the absence of myocardial infarction and the proper clinical setting confirm acute myocarditis. Negative antimyosin scintigraphy findings exclude active myocarditis.

The exact mechanism for myocardial injury in viral cardiomyopathy is controversial. Several mechanisms have been proposed based on animal models. Viruses affect myocardiocytes by direct cytotoxic effects and by cell-mediated (T-helper cells) destruction of myofibers. Other mechanisms include disturbances in cellular metabolism, vascular supply of myocytes, and other immunologic mechanisms.

Viral myocarditis may resolve over several months during the treatment of left ventricular systolic dysfunction. However, it can progress to a chronic cardiomyopathy. The main issue in recovery is ventricular size. Reduction of ventricular size is associated with long-term improvement; otherwise, the course of the disease is characterized by progressive dilation.

Because of an immunologic mechanism of myocyte destruction, several trials have investigated the use of immunomodulatory medications. (Other trials are currently being conducted.) According to Mason et al in 1995, the Myocarditis Treatment Trial demonstrated no survival benefit with prednisone plus cyclosporine or azathioprine in patients with viral (lymphocytic) myocarditis.[2] Randomized trials are under way to evaluate intravenous immunoglobulin as treatment for viral myocarditis.

Familial cardiomyopathy

Familial cardiomyopathy is a term that collectively describes several different inherited forms of heart failure. Familial dilated cardiomyopathy is diagnosed in patients with idiopathic cardiomyopathy who have 2 or more first- or second-degree relatives with the same disease (without defined etiology). Establishing a diagnosis with more-distant affected relatives (third degree and greater) simply requires identifying more family members with the same disease. Genetic screening has been recommended for patients fulfilling the above criteria.

A study by van Spaendonck-Zwarts et al suggested that a subset of peripartum cardiomyopathy is an initial manifestation of familial dilated cardiomyopathy. This may have important implications for cardiologic screening in such families.[3]

Several forms of familial cardiomyopathy have been described, and theories postulate its association with other causes of cardiomyopathy. Inheritance is autosomal dominant; however, autosomal recessive and sex-linked inheritance have been reported.

Several different genes and chromosomal aberrations have been described in studied families. One example is the gene that codes for actin, a cardiac muscle fiber component. Other forms of familial cardiomyopathy involve a strong association with conduction system disease. As research continues, the knowledge database regarding familial cardiomyopathies is likely to expand.

Doxorubicin-induced cardiomyopathy

Anthracyclines, which are widely used as antineoplastic agents, have a high degree of cardiotoxicity and cause a characteristic form of dose-dependent toxic cardiomyopathy. Both early acute cardiotoxicity and chronic cardiomyopathy have been described with these agents. Anthracyclines can also be associated with acute coronary spasm. The acute toxicity can occur at any point from the onset of exposure to several weeks after drug infusion. Radiation and other agents may potentiate the cardiotoxic effects of anthracyclines.

Cardiac injury occurs even at doses below the empiric limitation of 550 mg/m2. However, whether injury results in clinical CHF varies. The development of heart failure is very rare at total doses less than 450 mg/m2 but is dose dependent.

The history of these patients, in addition to having classic heart failure symptoms or symptoms of acute myocarditis, involves a previous history of malignancy and treatment with doxorubicin.

Anatomically, these patients' hearts vary from having bilaterally dilated ventricles to being of normal size. The mechanism of myocardial injury is related to degeneration and atrophy of myocardial cells, with loss of myofibrils and cytoplasmic vacuolization. The generation of free radicals by doxorubicin has also been implicated. Progressive deterioration is the norm for this toxic cardiomyopathy.

Prevention is based on limiting dosing after 450 mg/m2 and on serial functional assessments (ie, resting and exercise evaluation of ejection fraction). The drug should be discontinued if the ejection fraction is less than 0.45, if it falls by more than 0.05 from baseline, or if it fails to increase by more than 0.05 with exercise. Dexrazoxane is an iron-chelating agent approved by the FDA to reduce toxicity; however, it increases the risk of severe myelosuppression.

Cardiomyopathy associated with collagen-vascular disease

Several collagen-vascular diseases have been implicated in the development of cardiomyopathies. These include the following:

Rheumatoid arthritisSystemic lupus erythematosusProgressive systemic sclerosisPolymyositisHLA-B12–associated cardiac disease

Diagnosis is based on identification of the underlying disease in conjunction with appropriate clinical findings of heart failure.

Granulomatous cardiomyopathy (sarcoidosis)

Endomyocardial biopsy may be helpful in establishing the diagnosis, especially in sarcoidosis in which the myocardium may be involved. Involvement may be patchy, resulting in a negative biopsy finding. The diagnosis can also be made if some other tissue diagnosis is possible or available in conjunction with the appropriate clinical picture for heart failure. Cardiac involvement in sarcoidosis reportedly occurs in approximately 20% of cases.

Patients have signs and symptoms of sarcoidosis and CHF. Patients rarely present with CHF without evidence of systemic sarcoid. Bilateral mediastinal, paratracheal, and/or hilar lymphadenopathy may be evident.

Noncaseating granulomatous infiltration of the myocardium occurs as with other organs affected by this disease. Sarcoid granulomas can show a localized distribution within the myocardium. The granulomas particularly affect the conduction system of the heart, left ventricular free wall, septum, papillary muscles, and, infrequently, heart valves. Fibrosis and thinning of the myocardium occurs as a result of the infiltrative process affecting the normal function of the myocardium.

Diagnosis involves finding noncaseating granulomas from cardiac biopsy or other tissues. Often, patients present with conduction disturbances or ventricular arrhythmias. In fact, in patients with normal left ventricular function, these conduction disturbances may be the primary clinical feature.

Treatment of cardiac sarcoidosis with low-dose steroids may be beneficial, especially in patients with progressive disease, conduction defects, or ventricular arrhythmias. The true benefit is unknown because of the lack of placebo-controlled studies. This also holds true for the use of other immunosuppressive agents (eg, chloroquine, hydroxychloroquine, methotrexate) in the treatment of cardiac sarcoidosis.

Carnitine deficiency

A carnitine transporter defect is characterized by severely reduced transport of carnitine into skeletal muscle, fibroblasts, and renal tubules. All children with dilated cardiomyopathy or hypoglycemia and coma should be evaluated for this transporter defect because it is readily amenable to therapy, which results in prolonged prevention of cardiac failure. The prognosis for long-term survival in pediatric dilated cardiomyopathy is poor.

Tachycardia-induced cardiomyopathy

Generally, when detected early, this type of cardiomyopathy is reversible once treatment of the tachycardia is successful. Common etiologies include chronic untreated atrial fibrillation with rapid ventricular response and frequent (several thousand daily) premature ventricular contractions. Persistent tachycardia is known to lead to myocyte dysfunction and cardiomyopathy. If the tachycardia-induced cardiomyopathy is left untreated, the left ventricular dysfunction can become irreversible. The exact mechanisms by which tachycardia affects cell function are poorly understood. The following are possible mechanisms by which myocyte dysfunction arises from tachycardia:

Depletion of energy storesAbnormal calcium channel activityAbnormal subendocardial oxygen delivery secondary to abnormalities in blood flowReduced responsiveness to beta-adrenergic stimulationPreviousNextEpidemiology

The true incidence of cardiomyopathies is unknown. As with other diseases, authorities depend on reported cases (at necropsy or as a part of clinical disease coding) to define the prevalence and incidence rates. The inconsistency in nomenclature and disease coding classifications for cardiomyopathies has led to collected data that only partially reflect the true incidence of these diseases.

Whether secondary to improved recognition or other factors, the incidence and prevalence of cardiomyopathy appear to be increasing. The reported incidence is 400,000-550,000 cases per year, with a prevalence of 4-5 million people.

Cardiomyopathy is a complex disease process that can affect the heart of a person of any age, and clinical manifestations appear most commonly in the third or fourth decade.

PreviousNextPrognosis

Although some cases of dilated cardiomyopathy reverse with treatment of the underlying disease, many progress inexorably to heart failure. With continued decompensation, heart transplantation may be necessary.

The prognosis for patients with heart failure depends on several factors, with the etiology of disease being the primary factor. Other factors play important roles in determining prognosis; for example, higher mortality rates are associated with increased age, male sex, and severe CHF. Prognostic indices include the New York Heart Association functional classification.

The Framingham Heart Study found that approximately 50% of patients diagnosed with CHF died within 5 years.[4] Patients with severe heart failure have more than a 50% yearly mortality rate. Patients with mild heart failure have significantly better prognoses, especially with optimal medical therapy.

PreviousProceed to Clinical Presentation , Dilated Cardiomyopathy

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Myocardial Abscess

Background

Myocardial abscess is a suppurative (pus-containing) infection of the myocardium, endocardium, native or prosthetic valves or perivalvular structures, or the cardiac conduction system. In this serious and life-threatening disease, early recognition and institution of appropriate medical and surgical therapy is necessary for patient survival.

In the past, most cases of myocardial abscess were discovered at autopsy. The very first report, published in 1933, was an autopsy report by Cossio and colleagues that involved the finding of a pneumococcal abscess in the region of infarcted myocardial tissue as a complication of bronchopneumonia.[1] Several more such cases were reported later, suggesting that myocardial abscess often occurs in the setting of septicemia and abscesses in other locations. Myocardial abscess can now be detected antemortem using various noninvasive diagnostic modalities.

Infective endocarditis (IE) has become the most common condition underlying myocardial abscesses. This article addresses the presenting features, diagnostic tests, therapeutic interventions, and follow-up strategies for myocardial abscess.

NextPathophysiologyEndocarditis

Currently, the most common clinical setting for myocardial abscess is endocarditis of either native or prosthetic valves. In a review of 40 cases of infective endocarditis, Gonzalez Vilchez et al (1991) found that 67.5% (27 cases) involved native valves. The most common site was the aortic valve, followed in descending order by the ventricular septa, mitral valves, and papillary muscles. Approximately one third of cases involved the base of the aortic valve. Staphylococcus was the most prevalent species involved, isolated from one third of all cases. Prosthetic valve abscess comprised 34% of cases, and 50% of these were caused by staphylococcal infection.[2]

Bacteremia

In the past, the most common setting for myocardial abscess was generalized bacteremia, as described in older autopsy reports. Sanson and colleagues (1963) described 23 cases, 21 of which exhibited multiple abscesses in lungs, kidneys, brain, and myocardium. Myocardial abscesses were small in these patients, and the authors postulated that the patients died too early to develop larger abscesses.[3]

Site of myocardial infarction

Myocardial abscess may develop at the site of a myocardial infarction (MI) but usually develops in the setting of bacteremia. Cossio et al (1933) reported a myocardial abscess at the site of an acute MI.[1] In the case records of the Massachusetts General Hospital, Castleman and McNeely (1970) reported a secondary infection within an inferior wall MI in a patient with Bacteroides bacteremia following genitourinary surgery and placement of an infected indwelling catheter.[4]

In a review of 13 cases of myocardial abscess in acute MI, Weisz and Young (1977) found bronchopneumonia to be the probable source in 4 cases, gastrointestinal and renal sepsis in 2, and no definable source in the others. Organisms included Staphylococcus aureus, Clostridium perfringens, Bacteroides species, Escherichia coli, beta-hemolytic streptococci, and Streptococcus pneumoniae, in order of decreasing frequency.[5]

The propensity of cardiac muscle to develop myocardial abscess in the setting of acute MI and septicemia may be due to the presence of necrosis of the muscular fibers and surrounding inflammatory exudates, decreased or absent perfusion, and lack of cell-mediated immunity secondary to decreased blood flow. Such myocardium also appears to be at a greater risk of rupture than healthy myocardium (7-fold higher per Weisz and Young [1977][5] ), with a catastrophic outcome.

Other clinical settings

Other settings associated with myocardial abscesses that have been reported in the literature include the following:

TraumaDeep penetrating woundsDeep burnsInfected pseudoaneurysmsSuppurative pericardial effusionsInfected transplanted heartsExtension from sternal abscessHIV-associated myocarditis and suppurationParasitic infectionsInfection of a left ventricular aneurysm or tumorPreviousNextMicrobiology

Usually, a single type of organism acts as the causal agent. However, not uncommonly, these abscesses have a polymicrobial etiology. Sanson and associates (1963) reported that more than 40% of cases involve more than one microbial agent, usually staphylococci or E coli.[3] Whether this reflected a polymicrobial etiology or a single-organism etiology with subsequent polymicrobial overgrowth is unclear. The increase in antibiotic use in general creates a setting in which polymicrobial involvement may become even more common, especially in patients with diabetes mellitus.

PreviousNextMicroorganismsS aureusHaemophilus speciesEnterococciE coliBeta-hemolytic streptococciS pneumoniaeBacteroides speciesParasitic organismsHydatid cysts, ie, from echinococciMiscellaneousPreviousNextPathogenesis

Development of infective endocarditis and subsequent myocardial abscess involves interaction of multiple factors, as follows:

Vascular endotheliumHemostatic mechanismsHost immune systemGross anatomic abnormalities in the heartSurface properties of microorganismsExtracardiac events that introduce bacteremia

Each of these components is in itself complex, affected by many factors, and not fully understood. The rarity of endocarditis despite the relatively high prevalence of transient asymptomatic and symptomatic bacteremia suggests that the intact endothelium is resistant to infection. If the endothelium on the valve surface is damaged, hemostasis is stimulated and the deposition of platelets and fibrin complex begins. This complex, called nonbacterial thrombotic endocarditis (NBTE), is more susceptible to bacterial colonization when bacteremia develops from an extracardiac source that allows the organisms access to the NBTE.

The intracardiac consequences of endocarditis range from trivial, characterized by an infected vegetation with no attendant tissue damage, to catastrophic, when infection is locally destructive or extends beyond the valve leaflet. Distortion or perforation of valve leaflets, rupture of chordae tendineae, and perforations or fistulas may result in progressive congestive heart failure (CHF). Infection, particularly that involving the aortic valve or prosthetic valves, may extend into paravalvular tissue and result in myocardial abscesses and persistent fever due to the infection's unresponsiveness to the antibiotic; disruption of the conduction system, with electrocardiographic conduction abnormalities; and clinically relevant arrhythmias or purulent pericarditis.

PreviousNextEpidemiologyFrequencyUnited States

Myocardial abscess rarely occurs in the United States.

International

Murdoch et al (2009) published a contemporary report on the presentation, etiology, and outcome of infective endocarditis in a large patient cohort from multiple locations worldwide. They analyzed a prospective cohort study of 2781 adults (median age 57.9 y) with definite infective endocarditis (72.1% of the native valve) who were admitted to 58 hospitals in 25 countries over a 5-year period. Seventy-seven percent of the patients presented early in the disease course (ie, within the first month), with few of the classic clinical hallmarks of infective endocarditis. Recent health care exposure was found in one quarter of the patients.

S aureus was the most common pathogen found (31.2% of patients). The mitral valve was found to be infected in 41.1% of cases and the aortic valve in 37.6%. The common complications included stroke (16.9%), embolization other than stroke (22.6%), heart failure (32.3%), and intracardiac abscess (14.4%). Surgical therapy was performed in 48.2% of the patients, and in-hospital mortality rates were high (17.7%).

Several factors portended a high fatality risk, including prosthetic valve involvement (odds ratio [OR], 1.47), increasing age (OR, 1.30), pulmonary edema (OR, 1.79), S aureus infection (OR, 1.54), coagulase-negative staphylococcal infection (OR, 1.50), mitral valve vegetation (OR, 1.34), and paravalvular complications (OR, 2.25). Streptococcus viridans infection (OR, 0.52) and surgery (OR, 0.61) were associated with a decreased fatality risk. In summary, in the early 21st century, infective endocarditis continues to be more often an acute disease, characterized by a high rate of S aureus infection and an unacceptably high mortality rate.[6]

The incidence of infective endocarditis remained relatively stable from 1950-1987, at approximately 4.2 cases per 100,000 patient-years.[7] During the early 1980s, the yearly incidence of infective endocarditis was 2 cases per 100,000 population in the United Kingdom and Wales and 1.9 cases per 100,000 population in the Netherlands. A higher incidence was noted from 1984-1990; 5.9 and 11.6 episodes per 100,000 population were reported from Sweden and metropolitan Philadelphia, respectively.[8]

Infection involving mechanical prostheses often extends into the annulus and adjacent myocardium, resulting in paravalvular abscess formation and partial dehiscence of the prosthetic valve with paravalvular regurgitation. Among 85 patients with endocarditis involving a mechanical prosthesis, annulus invasion and myocardial abscess were noted in 42% and 14% of patients, respectively.[9] Ben Ismail et al (1987) found annulus infection and valve dehiscence in 38 of 41 (82%) infected mechanical valves examined at surgery or autopsy.[10] Mortality/Morbidity

Myocardial abscess formation profoundly worsens the prognosis in patients with infective endocarditis.

The mortality rate associated with S aureus infection is 42% overall. If treated with antibiotics only, the mortality rate is 75%. If treated with antibiotics and surgery, the mortality rate falls to 25%. The presence of an intracardiac abscess or complications increases the mortality rate 13.7-fold.Race

Myocardial abscess has no substantial racial predilection. The condition may be more prevalent in African Americans in urban settings.

Sex

The relative risk ranges from 3.5-8.2. Because mitral valve prolapse (MVP) is more common in women than in men, myocardial abscess is also more common in women than in men.

Among persons who abuse intravenous drugs, myocardial abscess is more prevalent in men (65%-80%).In adults, MVP has emerged as a prominent predisposing structural abnormality that may account for 7%-30% of cases of nonvalvular endocarditis (NVE). However, myocardial abscess developing in such cases is exceedingly rare. Age

Involvement of cardiac structures with endocarditis and myocardial abscess mainly depends on the incidence of various underlying structural heart conditions among different age groups.

The incidence of infective endocarditis among hospitalized children ranges from 1 case in 4500 to 1 case in 1280. In the Netherlands, incidences of 1.7 cases per 100,000 persons in boys and 1.2 cases per 100,000 persons in girls have been noted.[7] In neonates, the rate has been increasing because of contaminated intravenous lines and the increased use of right-sided heart catheters. Infective endocarditis usually involves the tricuspid valve and is caused primarily by S aureus. Congenital heart defects are predisposing conditions in toddlers and older children. In adults, MVP is the most common structural heart abnormality associated with infectious endocarditis, found in as many as 7%-30% of patients with NVE, and the risk increases in patients older than 45 years. Those who abuse intravenous drugs are increasingly susceptible (2%-5% per patient-year).PreviousProceed to Clinical Presentation , Myocardial Abscess

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Endomyocardial Fibrosis

Background

Endomyocardial fibrosis (EMF) is an idiopathic disorder of the tropical and subtropical regions of the world that is characterized by the development of restrictive cardiomyopathy.

The nosology of EMF coincides with some related disorders. EMF is sometimes considered part of a spectrum of a single disease process that includes Löeffler endocarditis (nontropical eosinophilic endomyocardial fibrosis or fibroplastic parietal endocarditis with eosinophilia).

Tropical EMF and Löeffler endocarditis should be distinguished from endocardial fibroelastosis, which is characterized by cartilaginous thickening of the mural endocardium, chiefly of the left ventricle. This disease is most common in the first 2 years of life and, in some patients, appears to be an inherited disorder that is associated with congenital cardiac malformations.

NextPathophysiology

In EMF, the underlying process produces patchy fibrosis of the endocardial surface of the heart, leading to reduced compliance and, ultimately, restrictive physiology as the endomyocardial surface becomes more generally involved. Endocardial fibrosis principally involves the apices of the right and left ventricles and may affect the atrioventricular valves mainly by tethering the papillary muscles, leading to tricuspid and mitral regurgitation.

The earliest changes of EMF are not well described because most patients do not present with symptoms until relatively late in the clinical course. Olsen described 3 phases of EMF. The first phase involves eosinophilic infiltration of the myocardium with necrosis of the subendocardium and a pathologic picture consistent with acute myocarditis. This is reportedly present in the first 5 weeks of the illness. The second stage, typically observed after 10 months, is associated with thrombus formation over the initial lesions, with a decrement in the amount of inflammatory activity present. Ultimately, after several years of disease activity, the fibrotic phase is reached, when the endocardium is replaced by collagenous fibrosis. This pathomorphologic schema is not observed uniformly and has not been consistently supported by other investigators.

Myocardial fibrosis consists of collagen deposition and fibroblast proliferation. These changes can potentially explain most of the symptoms in patients with EMF. Fibrosis increases the stiffness of the heart, resulting in the restrictive physiology. Ventricular stiffness along with atrioventricular valvular regurgitation results in atrial enlargement, which has been linked to atrial arrhythmias such as atrial fibrillation. Fibrosis also reduces conduction velocity, impairs activation pattern and may provide the substrate for wave breaks and reentry.[1] Recently, fibrosis has been suggested to facilitate focal activity by fibroblast-myocyte coupling as well.[2] Atrial fibrillation has been reported in more than 30% of patients with EMF followed by other rhythm or conduction abnormalities like junctional rhythm, heart blocks, and intraventricular conduction delay.[3]

While in general, fibrosis in cardiac tissue has been mainly linked to increased level of a cytokine, transforming growth factor-β1[4] ; the underlying mechanisms of myocardial fibrosis in this specific entity remain unclear. Hypotheses include infectious, inflammatory, and nutritional processes. EMF is frequently associated with concomitant parasitic infections (eg, helminths) and their attendant eosinophilia, although the role of parasitic infections and/or the eosinophil remains speculative. The development of EMF as a sequela to toxoplasma-related myocarditis has also been described, as has a relationship of malarial infection to development of EMF. However, no specific organism has been consistently associated with EMF.

The role of the eosinophil in the pathogenesis of EMF is controversial. Whether the eosinophil actually induces myocardial necrosis and subsequent fibrosis or is attracted to the endocardial surface as a result of the initial insult is unknown. Some authors have argued that in tropical eosinophilia, where the eosinophil count does climb to levels as high as 12,500/dL, endomyocardial fibrosis is rarely seen and the cardiac manifestations are limited, while severe eosinophilia is absent in EMF.[5] In general, the eosinophil is not present as frequently in cases of tropical EMF as in Löeffler endocarditis especially at later stages of the disease when the patient is symptomatic; thus, the role of the eosinophil in the tropical disease is likely less significant.

EMF is most frequently observed in the socially disadvantaged and in children and young women. These groups frequently have malnutrition, and in regions of sub-Saharan Africa where the disease is most prevalent, the typical diet is high in a tuber called cassava, which contains relatively high concentrations of the rare earth element cerium (Ce). The combination of high Ce levels and hypomagnesemia has been shown to produce EMF-like lesions in laboratory animals.

A familial tendency has rarely been noted in Uganda and Zambia.

PreviousNextEpidemiologyFrequencyUnited States

EMF is rarely encountered in patients who have not traveled from the subtropical regions of Africa and tropical and subtropical regions elsewhere in the world, including areas in India and South America that are within 15° of the equator. Löeffler endocarditis (also called nontropical eosinophilic endocarditis) is a related condition that is observed in the United States and is considered by some authors to be a different stage of a similar process related to eosinophilia.

International

EMF occurs primarily in the subtropical regions of Africa but is also encountered in tropical and subtropical regions elsewhere in the world, including areas in India and South America that are within 15° of the equator.

More than 90% of reported cases of EMF have occurred in geographic locations that are within 15° of the equator. In equatorial African nations, such as Nigeria, EMF is the fourth most common cause of cardiac disease in adults, and EMF accounts for 22% of cases of heart failure in Nigerian children. EMF is the most common type of restrictive cardiomyopathy in tropical countries and worldwide.

In a screening study in a rural area in Mozambique, approximately 20% of a random sample of 1063 subjects of all age groups had echocardiographic evidence of this disease.[6] In the same study, the prevalence was highest among persons aged 10-19 years, and the most common form was biventricular endomyocardial fibrosis followed by right-side dominant and then left-side dominant disease. Most other studies also reported higher prevalence of biventricular pattern while in some studies left ventricular dominant pattern has been more common than the right ventricular dominant pattern.[7]

Mortality/MorbidityThe overall prognosis of patients with EMF is poor and depends on the extent and distribution of disease within the various chambers and valves of the heart. The disease is usually progressive but the time course of decline varies. Most patients have extensive disease at the time of presentation; therefore, survival after diagnosis is relatively brief. In one study, 95% of a group of patients had died at 2 years. In a second study, 44% of patients died within 1 year after the onset of symptoms, and another 40% of patients died 1-3 years after onset. Death usually occurs as a result of progressive heart failure or associated arrhythmia and sudden cardiac death. Race

EMF is most commonly reported in individuals living in Nigeria and Uganda. Among residents of these countries, EMF appears to be more prevalent in certain ethnic groups. One study in Uganda showed that EMF is more common in individuals with Rwanda/Burundi ethnic origins.[8]

Sex

In general, women of reproductive age and children are more commonly affected than men. However, a recent screening study in a rural area of Mozambique reported a higher rate among male than female subjects (23.0% vs 17.5%, P =0.03).[6] This study was based on a screening echocardiography and many of these patients were not symptomatic.

AgeEMF is not generally observed in children younger than 4 years, although the typical pathology for EMF has recently been described in a 4-month-old infant with left ventricular inflow tract obstruction. The people most commonly affected are usually older children (aged 5-15 y) and young adults, but cases have been reported in individuals aged 70 years. PreviousProceed to Clinical Presentation , Endomyocardial Fibrosis

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Myocarditis Organism-Specific Therapy

Specific Organisms and Therapeutic Regimens

General recommendations and organism-specific therapeutic regimens for myocarditis are provided below, including those for viral[1, 2, 3, 4] and bacterial organisms.[2, 3, 5] Special considerations are also discussed.

General recommendations

Most cases of myocarditis are post viral in origin[6, 7] ; therefore, supportive therapy is first-line treatment.[2]

Obtain hemodynamic stability with vasopressors and inotropic agents, if needed.

Use diuretics and vasodilators if high ventricular filling pressures are noted on echocardiography.

Consider a left ventricular assist device, transplantation, or both in patients with severe disease.

Once the patient is stabilized, follow the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the treatment of heart failure.[1] Angiotensin-converting enzyme inhibitors (ACEIs), beta-blockade, and an aldosterone antagonist are recommended if the patient has New York Heart Association (NYHA) grade III-IV symptoms).[3, 5]

Diagnostic criteria

Endomyocardial biopsy is the criterion standard for diagnosis of myocarditis.[2, 8, 9]

Historically, the Dallas criteria have been used for histologic diagnosis, although their utility is questioned.

Elevated troponin I (>0.1 ng/mL) is highly specific for the diagnosis of myocarditis; the creatine kinase–muscle-brain (CK-MB) fraction and the total creatine kinase (CK) level are not useful.

Echocardiography is recommended as the initial imaging test of choice in suspected myocarditis.

Cardiac magnetic resonance imaging (MRI) is useful to differentiate between myocarditis and other cardiomyopathies, as well as to target endomyocardial biopsy sites.

Etiological classification

The classification of myocarditis based on etiology is shown in the chart below.[2, 8, 9]

Classification of myocarditis by etiology. Infectious causes and therapeutic guidelines

Viral:

Human immunodeficiency virus (HIV): Initiate antiretroviral therapy; for more information, see Antiretroviral Therapy for HIV Infection

Cytomegalovirus (CMV):

Induction therapy: Ganciclovir 5 mg/kg IV q12h for 7-14dMaintenance therapy: Valganciclovir 900 mg PO q24hDuration of therapy: Indefinite, but it may be stopped if the CD4 count is >100 for 6 months[10] Bacterial:

Borrelia burgdorferi:

First-degree atrioventricular (AV) block:

Doxycycline 100 mg PO q12h orAmoxicillin 500 mg PO q8h orCefuroxime 500 mg PO q12hDuration of therapy: 14-21d

Symptomatic, second- or third-degree AV block:

Ceftriaxone 2 g/day IV orCefotaxime 2 g IV q8hDuration of therapy: 14-28 days[4]

Mycoplasma pneumoniae:

Doxycycline 100 mg PO q12h orAzithromycin 500 mg PO q24h orLevofloxacin 500 mg IV or PO q24h orMoxifloxacin 400 mg PO q24h orErythromycin 250 mg PO q6hDuration of therapy: 14-21d

Methicillin-resistant Staphylococcus aureus (MRSA):

Vancomycin 15-20 mg/kg/dose IV q8-12h (not to exceed 2 g/dose) (A-II) orDaptomycin 6 mg/kg/dose IV once daily (A-I) for at least 2-6 weeks[11]

Corynebacterium diphtheriae:

Erythromycin 40 mg/kg/day PO/IV in divided doses for 14 days; not to exceed 2 g/day orPenicillin G procaine 600,000 U IM for 14d; if weight [12] Parasite:

Babesiosis:

Atovaquone 750 mg PO q12h plus azithromycin 500-1000 mg PO on day 1, then 250 mg once daily for 7-10d orClindamycin 300-600 mg IV q6h or 600 mg PO q8h plus quinine 650 mg PO q6-8h for 7-10 days Clindamycin and quinine should be given for those with severe babesiosis[4]

Schistosoma mansoni, Schistosoma haematobium, Schistosoma intercalatum:

Praziquantel 20 mg/kg PO for 2 doses within 1 day[13, 14] Protozoa:

Trypanosoma cruzi:

Benznidazole 5-7 mg/kg/day PO in 2 divided doses for 60 days (investigational in the United States; available from the CDC)Nifurtimox 8-10 mg/kg/day PO in 3 or 4 divided doses for 90 days[15]

Clinical therapeutic considerations for myocarditis scenarios [2, 8, 9, 16]

See the acute myocarditis flow chart (first image below) and subacute myocarditis flow chart (second image below).

Acute myocarditis treatment flowchart. Subacute myocarditis treatment flowchart.

Forty percent of dilated cardiomyopathy patients not responding to treatment have myocarditis.[17, 18]

Ten percent of unexplained myocarditis cases are post viral in origin.[6, 7]

The prognosis depends on spontaneous complete resolution (acute fulminant myocarditis) or the development to dilated cardiomyopathy.[19, 20]

Inflammation has beneficial effects on clearing the viral particles; hence, immune suppression is not generally recommended.[21]

Infection with enterovirus and adenoviruses could be treated with 6 mIU interferon 3 times a week to reduce the viral load and improve ventricular function during an acute myocarditis episode.[9]

Studies investigating intravenous immunoglobulin (IVIG) therapy in adults with acute myocarditis and acute myopathy have failed to show any type of usefulness in treatment during an acute episode.

In patients with HIV infection, a long-term follow up (at 5 y) with echocardiogram has shown that 8% show dilated cardiomyopathy changes.[22] However, it is unknown if ACEIs and beta-blockers are effective in these patients.

Autoimmune and hypersensitivity

Giant cell myocarditis is the only known cause of most fulminant heart failure with ventricular arrhythmias.[23, 24] Immunosuppression and mechanical cardiac support are recommended in this case and, possibly, cardiac transplantation, with a 20-25% recurrence rate post transplantation. Immunosuppression may have beneficial effects to some extent.[25]

Hypersensitivity-related myocarditis often manifests as infiltration with lymphocytes, histocytes, and eosinophil, and sometimes it results in sudden death from complications of myocarditis.

Complications

Myopericarditis with acute coronary syndrome is a potential complication. Treat inflammation with colchicine at 2 mg/day PO with stepwise dose reduction, which should improve pericarditis in 3 months; NSAIDs are contraindicated in this condition.[26, 27]

Syncope with ventricular arrhythmia and cardiac block should be treated with hospital admission with continuous echocardiogram monitoring and conservative management, similar to acute arrhythmias.

Cardiogenic shock may require mechanical ventilator support, extracorporal membrane oxygen therapy, and cardiac transplantation.[28, 29]

, Myocarditis Organism-Specific Therapy

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Constrictive-Effusive Pericarditis

Overview

Effusive-constrictive pericarditis is a rare clinical syndrome characterized by concurrent pericardial effusion and pericardial constriction, with constrictive hemodynamics being 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]

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

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 on 15 subjects from Barcelona, Spain who were identified as having effusive-constrictive pericarditis.[11] 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.

Pericardial effusion

The pericardium consists of 2 layers, a parietal layer and a 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 supraphysiologic accumulation of this fluid is identified as a pericardial effusion.[1, 2, 12, 13, 14] In general, a pericardial effusion should be evaluated to determine its etiology and hemodynamic significance.

Hemodynamics

Jugular venous and arterial pressures may be within the reference range, with or without signs of cardiac tamponade. Effusive-constrictive pericarditis is believed to 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.

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, 11]

Treatment considerations

Recognition of effusive-constrictive pericarditis is clinically important because treatment with pericardiocentesis or a pericardial window may be inadequate; this is because neither treatment would address the visceral pericardium. Rather, a visceral pericardiectomy may be indicated for optimal therapy since it is the visceral pericardium that is constricting.

Importantly, however, not all cases of effusive-constrictive pericarditis progress to chronic constrictive pericarditis. In some clinical situations, relief from the effusion can be obtained by means of pericardiocentesis or a pericardial window, with medical treatment being 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.

Patient education

Although the symptoms of effusive-constriction are nonspecific, patients should be counseled to report any new or worsened dyspnea, ascites, weight loss or gain, peripheral edema, fever, or chest pain or pressure.

NextPathophysiology

Constrictive pericarditis and cardiac tamponade both restrict filling of the cardiac chambers, thereby increasing 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 tamponade-like pressure tracings, which change to constrictive-like tracings after pericardiocentesis. This is because the visceral, rather than the parietal, pericardium 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.

PreviousNextEtiology

Effusive-constrictive pericarditis likely occurs at any point along a clinical continuum that ranges from the occurrence of an effusion to the development of chronic pericardial constriction. Leading causes of effusive-constrictive pericarditis include the following:

Idiopathic factorsIrradiationCardiac surgeryNeoplasm - Most commonly lung, breast, or hematologicInfectious disease - Particularly in immunocompromised states (most commonly tuberculosis and fungal disease, although Streptococcus species have been reported)[15, 16] Myocardial infiltrationConnective tissue diseaseUremia

Cases of effusive-constrictive pericarditis in the United States are most often secondary to irradiation, cardiac surgery, uremia, or malignancy or are idiopathic.[6] In developing countries, the disorder is usually secondary to infectious causes (eg, tuberculosis).[17] 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.[11]

The disorder’s 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 of the causes for pericardial effusions and pericardial tamponade and then a determination of whether a particular patient has constrictive physiology.

PreviousNextPrognosis

Mortality associated with effusive-constrictive disease is directly related to its etiology. For example, patients with metastatic carcinoma in the pericardial space usually have a prognosis that is much poorer than that of patients with postviral or idiopathic pericardial effusion with constriction. Noncardiac metastatic effusions are often end-stage, with reported mortality rates of 47% and 80% at 3 and 6 months, respectively.

Constrictive physiology increases the risk of morbidity in patients with effusive-constrictive pericarditis, but no definitive statistics are available.

The most effective therapy for effusive-constrictive pericarditis is pericardiectomy with complete removal of the parietal and visceral membranes. However, the perioperative mortality rate for this procedure can be high. Indeed, only experienced surgeons should undertake visceral pericardiectomy.[18]

When visceral pericardiectomy is not chosen as the plan of care, the underlying disease may progress and cause recurrent and/or worsening effusive-constrictive syndrome or constrictive pericarditis.

PreviousNextPatient History

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 disease stages. 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 can suggest pericardial disease (eg, tuberculosis, renal failure, malignancy, radiation therapy, cardiovascular surgery).[2]

PreviousNextPhysical Examination

Physical findings may exist on a continuum, including findings common with cardiac tamponade.[19] Findings may include hypotension, jugular venous distension, and diminished heart sounds (classic Beck triad). (The classic description of percussible cardiac dullness at the apex may be unreliable.)

Other common findings can include the following:

Pulsus paradoxus (paradoxical pulse)Jugular venous pulse with a prominent x descent and absent y descentTachycardiaTachypneaHepatomegalyAscitesPeripheral edemaPleural effusion (in the absence of left-sided congestive signs)Renal dysfunctionLiver dysfunction and/or auscultation of a pericardial friction rub

Careful attention to all physical findings is required to find clues to theunderlying etiology of the pericardial disease.

PreviousNextDifferential Diagnosis

Because effusive-constrictive pericarditis is rare, the differential diagnosis is guided by few published series and case reports. Differentials to consider include the following:

Postradiation syndromesNeoplasias (metastatic)Hematologic neoplasiasImmunocompromised states with infectionConnective tissue diseaseUremiaBreast CancerCardiac tamponadeRestrictive cardiomyopathyHypothyroidismMyocardial infarctionPenetrating chest traumaPericardial effusionAcute pericarditisConstrictive pericarditisUremic pericarditisTuberculosisPreviousNextLab Studies

Laboratory studies for effusive-constrictive pericarditis include tests of serum complete blood count (CBC) with differential and serum chemistries, with additions depending on the suspected etiology.

The most important laboratory studies are those performed on pericardial fluid (always under the assumption that pericardiocentesis is clinically indicated). The following tests should always be sent on an initial pericardiocentesis[20] :

Hematocrit and cell count with differentialCulture - Including tuberculosisGlucoseTotal proteinEnzymes - Lactate dehydrogenase, adenosine deaminaseGram stainingCytology

The need for other, more specific laboratory tests, including the following, is determined by the priorities of the differential diagnosis:

Suspected tuberculous pericarditis - Purified protein derivative (PPD) of tuberculin, appropriate staining of pericardial fluid Suspected infectious pericarditis - Serum aerobic and anaerobic blood cultures, viral titers, or polymerase chain reaction (PCR) assay of pericardial fluid Suspected malignancy - Pericardial fluid for tumor markers or carbohydrate antigens (CAs; eg, CA-125)Suspected human immunodeficiency virus (HIV) pericarditis - Serum HIV testingSuspected hypothyroid-related pericarditis - Serum thyroid function testingSuspected connective tissue disease - Serum connective tissue serologiesPreviousNextChest Radiography

The chest radiograph may consistently show an enlarged cardiac silhouette when the pericardial effusion is greater than 250mL. The cardiac silhouette may be flask shaped and the lung fields may show no evidence of congestion, consistent with the absence of a congestive cardiomyopathy.[21]

These findings must be interpreted with caution, as they may also be observed in severe aortic insufficiency, congestive heart failure with severe tricuspid insufficiency, severe volume overload, and mitral regurgitation. The distinguishing characteristic is pulmonary vascular congestion, which may be present with any of these conditions and is usually absent in pericardial disease.

A small effusion may have a normal cardiac silhouette, but this does not eliminate the diagnosis of effusive-constrictive pericarditis.

PreviousNextEchocardiography

Echocardiography is the most efficient way to detect an effusion because it has excellent sensitivity and specificity.[17, 22] Pericardial fluid is easily observed as an echolucent region (echo-free space) between the visceral pericardium (epicardium) and the parietal pericardium.

The size of the effusion may be estimated, even if the effusion is localized. For example, small effusions usually must be observed in 2 views, particularly behind the left ventricle. Moderate effusions are visualized circumferentially, and large effusions exceed 1cm in thickness on all views.

Doppler investigation may demonstrate increased respiratory variation of mitral and tricuspid inflow, consistent with constrictive pericarditis. Other echocardiographic findings consistent with constrictive pericarditis include abnormal septal and posterior wall motion, noted in the M-mode by using a parasternal short-axis view; a normal velocity of propagation (V p) in color M-mode; and a normal or supranormal early relaxation (Ea) on tissue Doppler imaging.

Echocardiography can also be used to distinguish a pericardial effusion from a pleural effusion, with pericardial effusions being anterior to the descending aorta.

In addition, evidence for cardiac tamponade may be inferred from an echocardiogram. For example, early diastolic collapse of the right ventricular free wall and/or late diastolic collapse of the right atrium may be observed.

PreviousNextCT Scanning, PET Scanning, and MRI

The diagnosis of effusive-constrictive pericarditis cannot be made primarily on the basis of computed tomography (CT) or magnetic resonance imaging (MRI) scan findings. However, CT scanning and MRI may provide excellent images of the pericardium and associated mediastinal structures.

CT scanning and MRI can be used to effectively image and confirm a thickened pericardium or detect a pericardial effusion if visualization with echocardiography is suboptimal. However, some patients with effusive-constrictive pericarditis have normal pericardial thickness; in such cases, the disease must be diagnosed hemodynamically.

The use of18 F-2-deoxyglucose (FDG) positron emission tomography (PET) scanning has been reported for the assessment of pericardial inflammation. The clinical use of PET imaging in effusive-constrictive pericarditis remains untested.[23]

PreviousNextElectrocardiography

An electrocardiogram (ECG) may not show any specific findings for effusive-constrictive pericarditis. However, the ECG may show changes in the ST segment, T wave, or PR segment and/or demonstrate low QRS voltage associated with pericarditis and/or effusion. Nonspecific ST- and T-wave abnormalities may be present.

With a large effusion, a cardiac rocking motion may be observed on the ECG as electrical alternans.

PreviousNextPericardiocentesis and Pericardial BiopsyPericardiocentesis

Pericardiocentesis as a diagnostic test may have a low yield, yet as a therapeutic procedure its diagnostic benefit is much improved. The risks and benefits of any invasive procedure must be considered before the start of testing.

Pericardial biopsy

Clinical circumstances determine when a biopsy is performed since procedural risk is increased. Factors include how symptomatic the patient is and how likely a finding would change clinical management.

Pericardioscopy is a developing technique that allows direct viewing of the epicardium with the possibility for biopsy. This is currently an experimental technique.[24]

Histologic findings

Pericardial biopsy samples may be examined for malignancy and inflammation by traditional and immunohistologic means. In advanced laboratories, PCR assay or in situ hybridization may be used to analyze for microbial deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). Combined examination of pericardial fluid and biopsy results provides the greatest yield.

PreviousNextHemodynamic Assessment

The diagnosis of effusive-constrictive pericarditis may be suspected clinically, but it is definitively established by recording right heart and intrapericardial pressures before and after pericardiocentesis.[1]

Before pericardial fluid is removed, cardiac tamponade (or near tamponade) hemodynamic physiology must be present to make the diagnosis of effusive-constrictive pericarditis. Hemodynamic pressure recordings will indicate that intrapericardial pressures, right atrial pressure, and end-diastolic right and left ventricular pressures are elevated and equal (or nearly equal). There is usually an inspiratory decrease in right-heart filling pressures. A prominent x descent and an absent y descent may also be noted.

Pericardiocentesis should decrease intrapericardial pressure to zero but may fail to restore cardiac hemodynamics to normal. This is because the visceral constrictive component of the syndrome causes a persistent elevation and equalization of intracardiac diastolic pressures. This constrictive physiology unveils a biphasic pressure tracing in the right atrium, now with a prominent y descent and dip-and-plateau right ventricular pressure tracings, with absent or minimal respiratory variation.

Put another way, persistent constriction after pericardiocentesis suggests a constrictive visceral pericardium and, therefore, the diagnosis of effusive-constrictive pericarditis.

Diagnostic consideration

Because effusive-constrictive pericarditis is rare, intrapericardial pressures are not routinely measured during pericardiocentesis in clinical practice. This protocol may result in failure to recognize intrapericardial pressure as near zero. The consequences of this oversight include missing the diagnosis of effusive-constrictive pericarditis.

PreviousNextPharmacologic Therapy

Although potentially curative therapy for hemodynamically compromising effusive-constrictive pericarditis requires surgical intervention, medical management directed at the underlying etiology may be effective, as dictated by clinical circumstances. However, no randomized, blinded clinical trials have been completed to guide medical therapy, which is primarily supportive.

Depending on putative etiology, steroids, nonsteroidal anti-inflammatory agents, or antibiotics may be needed.[25]

Intravascular volume status must not be decreased excessively in the presence of tamponade physiology; diuretics must not be applied indiscriminately. On the other hand, after pericardial drainage, diuretics may be useful with constrictive physiology and evidence of volume overload.

PreviousNextDrainage, Thoracotomy, and Pericardial Window

Pericardiocentesis or surgical drainage of the effusion is performed as dictated by the patient's clinical situation. These procedures are undertaken in circumstances of tamponade or hemodynamic compromise or when a purulent effusion is suspected, as well as in cases in which there is a large, persistent effusion or diagnostic uncertainty exists.[26]

The most effective therapy for effusive-constrictive pericarditis is pericardiectomy, with complete removal of the parietal and visceral membranes. The perioperative mortality rate for this procedure can be high. Surgery can be risky and requires considerable thought before it may be recommended. Difficulties include the length of the procedure, infection potential, morbidity secondary to the wide exposure required, other medical problems that are often present in these patients, and the technical expertise required to perform the surgery.

In patients who may have a high mortality risk with thoracotomy yet have a significant chance of effusion recurrence with needle drainage alone, a pericardial-peritoneal window is an effective treatment for recurrent pericardial effusions.[27]

PreviousNextInpatient and Outpatient CareInpatient care

If hemodynamic compromise is possible, inpatient care is required to monitor the patient. Moreover, necessary pericardial procedures usually involve hospitalization.

Transfer is required when necessary diagnostic or therapeutic modalities such as echocardiography, pericardiocentesis, or cardiothoracic surgery are not available at the treating facility.

Outpatient care

The priorities of outpatient care reflect the treatments required for specific etiologies and include monitoring patients for signs of worsening constrictive physiology or for the development of cardiac tamponade.

In general, patients are given maintenance therapy with a diuretic to maintain euvolemia. Other medications depend on the specific etiology being treated.

PreviousNextConsultations

A cardiologist can assist with echocardiographic interpretation, pericardiocentesis, and invasive hemodynamics. A cardiothoracic surgeon may help when a pericardial window or pericardiectomy is being considered.

In complicated cases, such as those involving tuberculous pericarditis or purulent uremic pericarditis, multidisciplinary involvement may be required. Specialists in infectious disease, nephrology, cardiology, and/or cardiothoracic surgery may be consulted.

PreviousNextDiet and Activity

No specific dietary changes are recommended. However, patients with effusive-constrictive pericarditis often have chronic underlying diseases for which adequate nutrition is especially important. Moreover, euvolemia is a goal, and salt restriction may be indicated.

The patient’s activities are generally limited by the underlying disease or the decreased cardiac output that may occur with effusive-constriction, but no specific activity prohibitions exist.

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