eMedicine Specialties > Cardiology > Myocardial Disease and Cardiomyopathies

Cardiomyopathy, Alcoholic

Eric D Popjes, MD, Assistant Professor, Department of Medicine, Division of Cardiology, Penn State Milton S Hershey Medical Center
Frank E Silvestry, MD, Director, PENN Cardiac Care at Radnor; Assistant Professor, Department of Medicine, Division of Cardiovascular Disease, University of Pennsylvania Health System

Updated: Mar 13, 2008

Introduction

Background

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).

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), sudden death, hypertension, and stroke. 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. 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).

Pathophysiology

To identify the causative agent, 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 both 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. The 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 alcoholic cardiomyopathy (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 contributer 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 also 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.

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, observed throughout the heart, and may be exaggerated under stressful conditions.

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 drink more than 2 drinks per day have a 1.5- to 2-fold increase in hypertension compared to 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 those who abuse alcohol, and it should be differentiated from pure forms of AC.

Sex

Based on currently available data, 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 (ie, 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 with alcohol abuse and reported a similar prevalence of cardiomyopathy between the sexes, but a lower total lifetime alcohol dose in women.¹
• In 1995, Urbano-Marquez described similar results in a group of 50 women and 100 men with alcohol abuse and 50 women who did not abuse alcohol (ie, controls). They reported a lifetime dose of alcohol in women that was 60% of that in men, but an equal incidence of cardiomyopathy and myopathy.²
• Based on their work with a rat model, Jankala and colleagues have suggested a link between lower levels of p53 mRNA expression and female susceptibility to the development of AC.³

Age

• Long-term alcohol use has been implicated as the etiology of LV dysfunction in as many as one third of cases of DC.
• Alcoholic cardiomyopathy is a disease that primarily affects persons of at least middle age and is observed less commonly in those younger than 40 years, although preclinical cardiac abnormalities have been demonstrated in persons with 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.

Clinical

History

• Similar to the pathological 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.
  • 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.
  • 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 those 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.⁴
  • In 1986, Richardson et al evaluated 38 patients with nonischemic dilated cardiomyopathy (DC). Of these persons, 18 were classified as heavy drinkers (ie, 80 g/d or 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. They concluded that continuous, rather than episodic, drinking was the major risk factor for the development of heart failure and that this effect was unrelated to the hypertensive effect of alcohol.⁵
  • Other studies and reviews have also quoted quantities similar to those mentioned above, and the type of beverage consumed appeared to be irrelevant.

Physical

• Physical examination findings are nonspecific and are not unique compared with findings of dilated cardiomyopathy 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 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 a direct effect of chronic alcohol consumption.
• See Histological Findings.

Causes

See Pathophysiology and Histological Findings.

Differential Diagnoses

Other Problems to Be Considered

Causes of dilated cardiomyopathy (DC) commonly sought during a workup for heart failure are as follows:

Coronary artery disease and ischemia
Long-standing hypertension
Infections (eg, viral [HIV], bacterial, parasitic)
Collagen vascular disease and vasculitides
Infiltrative disease (eg, amyloidosis, sarcoidosis, hemochromatosis)
Metabolic disease (eg, nutritional abnormalities, thyroid disease, diabetes, uremia)
Toxicities (eg, heavy metals, chemotherapeutic agents, cocaine, alcohol)
Muscular dystrophies and late-stage hypertrophic cardiomyopathy
Postpartum
Idiopathic

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, recent data have shown that this almost certainly is not the case.

Estruch et al evaluated (1) 30 men with alcohol abuse and cardiomyopathy, (2) 30 men with alcohol abuse without cardiomyopathy, (3) 20 persons with alcohol abuse and cirrhosis who were actively drinking, (4) 15 persons with alcohol abuse and cirrhosis who abstained from alcohol, and (5) 15 persons without alcohol abuse with cirrhosis of other etiologies. Of the patients in group 1, 43% had evidence of cirrhosis. In group 2, 6% had evidence of cirrhosis. In group 3, 50% had evidence of DC. Cardiac evaluation of all patients in group 5 yielded normal results.⁶

Estruch et al concluded that (1) those who abuse alcohol and have cardiomyopathy have a higher incidence of cirrhosis compared to those who do not have cardiac dysfunction, (2) those with cirrhosis have a high incidence of cardiac dysfunction, and (3) those who drink but have liver disease and have abstained from alcohol have a low incidence of cardiac disease.⁶

Workup

Laboratory 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 dilated cardiomyopathy (DC).
  • Results from an evaluation 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 compared to 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.

Imaging 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) scan, positron emission tomography scan) may be useful for evaluating cardiac size and function and for screening for coronary disease.
• 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 overall heart size and function, but on valvular structure and function, wall motion and thickness, and pericardial disease.
  • Echocardiographic findings in persons with AC are similar to those in persons with idiopathic DC.
  • Echocardiographic findings in persons with AC are as follows:
    • Four-chamber dilatation
    • Globally decreased ventricular function
    • Mitral and tricuspid regurgitation
    • Pulmonary hypertension
    • Evidence 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 hypertrophy

Other Tests

• ECG 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 incidence is increased following weekends and during holiday seasons.
  • Other supraventricular tachyarrhythmias and sudden death have also been associated with alcohol use and 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.

Procedures

• 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 and 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 pharmacological 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.

Histologic Findings

Although the qualitative properties of AC and other forms of DC may be similar, quantitative differences may exist. Teragaki and colleagues compared 20 patients with AC and 10 patients with DC.⁷ They 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.⁸ In the 1989 study by Urbano-Marquez et al, a comparison of symptomatic to asymptomatic patients revealed more extensive fibrosis in patients with symptoms.⁴ Others have looked at immunohistologic markers and have suggested that the presence of these markers might suggest an inflammatory process such as myocarditis, and their absence may point more toward AC or an idiopathic etiology.

Ultimately, AC is a clinical diagnosis made in a patient presenting with the 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.

• Inhibition of protein synthesis
• Inhibition of oxidative phosphorylation
• Fatty acid ester accumulation
• Free radical damage
• Inhibition of calcium-myofilament interaction
• Inflammatory and immunological factors
• Receptor abnormalities
• Disruption of cell membrane structure
• Coronary vasospasm
• Synergy with concomitant conditions

Treatment

Medical Care

• The mainstay of therapy for alcoholic cardiomyopathy (AC) is to treat the underlying cause, ie, complete and perpetual abstinence from all alcohol consumption. The efficacy of abstinence has been shown in those with early disease (eg, prior to the onset of severe myocardial fibrosis) and in those 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, digoxin for those with symptomatic LV dysfunction, and 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:
  • Abstaining from alcohol
  • Vasodilators - ACE inhibitors, angiotensin receptor blockers (the work of Cheng and colleagues in 2006 suggested that ARBs may prevent the development of AC⁹ ), nitrates, hydralazine
  • Digoxin
  • Diuretics
  • Beta-blockers
  • Anticoagulation (possibly)
  • Intravenous inotropic agents
  • Cardiac transplantation

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Angiotensin-converting enzyme (ACE) inhibitors

Recommended for patients with systolic heart failure. Slow the progression of heart failure and improve survival rates.

Ramipril (Altace)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Dosing

Adult

2.5 mg PO bid initially; titrate up to 5 mg bid or 10 mg qd, when possible

Pediatric

Not established

Interactions

NSAIDs may reduce hypotensive effects of ramipril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases ramipril levels; probenecid may increase ramipril levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics

Contraindications

Documented hypersensitivity; history of angioedema

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe congestive heart failure

Lisinopril (Prinivil, Zestril)

Prevents conversion of angiotensin I to angiotensin II (a potent vasoconstrictor), resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Dosing

Adult

10 mg/d PO qd or divided bid; increase by 5-10 mg/d at 1- to 2-wk intervals; not to exceed 80 mg/d

Pediatric

Not established

Interactions

NSAIDs may reduce hypotensive effects of lisinopril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases lisinopril levels; probenecid may increase lisinopril levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe congestive heart failure

Benazepril (Lotensin)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Dosing

Adult

20-40 mg/d PO qd or divided bid; make dose adjustments prn

Pediatric

Not established

Interactions

May increase digoxin, lithium, and allopurinol levels; probenecid may increase levels; coadministration with diuretics increases hypotensive effects; NSAIDs decrease effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe CHF

Captopril (Capoten)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Dosing

Adult

6.25-12.5 mg PO tid; not to exceed 150 mg tid

Pediatric

Not established

Interactions

NSAIDs may reduce hypotensive effects; may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; hypotensive effects may be enhanced when given concurrently with diuretics

Contraindications

Documented hypersensitivity; renal impairment

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe CHF

Enalapril (Vasotec)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Dosing

Adult

2.5-5 mg/d PO (increase prn)
Dosing range: 10-40 mg/d PO in 1-2 divided doses
Alternatively, 1.25 mg/dose IV over 5 min q6h

Pediatric

Not established

Interactions

NSAIDs may reduce hypotensive effects; may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; hypotensive effects may be enhanced when given concurrently with diuretics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe CHF

Angiotensin II receptor antagonists

Interfere with the binding of formed angiotensin II to its endogenous receptor.

Candesartan (Atacand)

Blocks vasoconstriction and aldosterone-secreting effects of angiotensin II. May induce more complete inhibition of renin-angiotensin system than ACE inhibitors, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. Use in patients unable to tolerate ACE inhibitors.

Angiotensin II receptor blockers reduce blood pressure and proteinuria, protecting renal function, and delaying onset of end-stage renal disease.

Dosing

Adult

8-16 mg/d PO initially; not to exceed 32 mg/d

Pediatric

Not established

Interactions

May increase digoxin, lithium, and allopurinol levels; probenecid may increase candesartan levels; coadministration with diuretics, increase hypotensive effects; NSAIDs may reduce hypotensive effects of candesartan; may increase risk of hyperkalemia if taken concurrently with potassium supplements or other potassium-sparing diuretics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal impairment (serum creatinine >3.5), valvular stenosis, or severe congestive heart failure; watch for serum potassium

Valsartan (Diovan)

For patients unable to tolerate ACE inhibitors. May induce more complete inhibition of renin-angiotensin system than ACE inhibitors. Do not affect response to bradykinin and are less likely to be associated with cough and angioedema.

Dosing

Adult

40-320 mg PO qd or in divided doses

Pediatric

Not established

Interactions

May increase digoxin, lithium, and allopurinol levels; probenecid may increase valsartan levels; coadministration with diuretics increase hypotensive effects; NSAIDs may reduce hypotensive effects of valsartan; may increase risk of hyperkalemia if taken concurrently with potassium supplements or other potassium-sparing diuretics

Contraindications

Documented hypersensitivity; severe hepatic insufficiency; biliary cirrhosis or obstruction; primary hyperaldosterism; bilateral renal artery stenosis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in hyperkalemia, suspected bilateral renal artery stenosis (RAS), or solitary kidney with unilateral RAS

Cardiac glycosides

Decrease AV nodal conduction primarily by increasing vagal tone. Used primarily in the setting of AF and atrial flutter with CHF.

Digoxin (Lanoxicaps, Lanoxin)

Used in patients with symptomatic LV dysfunction. Has direct inotropic effects in addition to indirect effects on the cardiovascular system. Acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.

Dosing

Adult

0.125-0.375 mg PO qd

Pediatric

<5 years: Not established
5-10 years: 20-35 mcg/kg PO
>10 years: 10-15 mcg/kg PO
Maintenance dose: Use 25-35% of PO loading dose

Interactions

IV calcium may produce arrhythmias in digitalized patients; medications that may increase levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil
Medications that may decrease serum levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, and procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid

Contraindications

Documented hypersensitivity; beriberi heart disease, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, and carotid sinus syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypokalemia may reduce positive inotropic effect; hypercalcemia predisposes patient to digitalis toxicity, and hypocalcemia can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis; adjust dose in renal impairment; highly toxic (overdoses can be fatal)

Beta-adrenergic blockers

For use in stable patients without decompensated heart failure and patients with symptoms despite treatment with an ACE inhibitor and diuretic. May improve heart function, probably by blocking effects of sympathetic nervous system.

Metoprolol (Lopressor, Toprol XL)

Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions.

Dosing

Adult

25 mg PO qd; may increase dose prn

Pediatric

Not established

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine

Contraindications

Documented hypersensitivity; uncompensated CHF, bradycardia, asthma, cardiogenic shock, and AV conduction abnormalities

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG

Carvedilol (Coreg and Coreg CR)

Nonselective beta- and alpha- adrenergic blocker. Does not appear to have intrinsic sympathomimetic activity. May reduce cardiac output and decrease peripheral vascular resistance.

Dosing

Adult

3.125 mg PO bid for 2 wk initially; then increase to 6.25 mg PO bid for 2 wk; double dose q2wk as tolerated, not to exceed 25 mg bid if <85 kg or 50 mg bid if >85 kg
Note: Dose of digitalis, diuretics, or ACE inhibitors must be stabilized prior to initiation

Pediatric

<18 years: Not established
>18 years: Administer as in adults

Interactions

Rifampin, barbiturates, cholestyramine, colestipol, NSAIDs, salicylates, and penicillins may decrease effects; may increase effects of antidiabetic agents, digoxin, and calcium channel blockers; concurrent administration with clonidine may increase blood pressure and decrease heart rate; may decrease effect of sulfonylureas; cimetidine, fluoxetine, paroxetine, and propafenone may increase levels

Contraindications

Documented hypersensitivity; hypotension; bradycardia; AV/SA node disease; cardiogenic shock; overt cardiac failure

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in CHF being treated with digitalis, diuretics, or ACE inhibitors (AV conduction may be slowed); discontinue if liver impairment occurs; caution in peripheral vascular disease, hyperthyroidism, and diabetes mellitus

Bisoprolol (Zebeta)

Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions.

Dosing

Adult

5 mg PO qd; may increase to 10 mg and then to 20 mg qd prn

Pediatric

Not established

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine

Contraindications

Documented hypersensitivity; uncompensated CHF, bradycardia, asthma, cardiogenic shock, and AV conduction abnormalities

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG

Diuretics

May improve symptoms of venous congestion through elimination of retained fluid and preload reduction.

Furosemide (Lasix)

Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.
Dose must be individualized to patient. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after previous dose, until desired diuresis occurs. When treating infants, titrate with increments of 1 mg/kg/dose until a satisfactory effect is achieved. Diuretics have major clinical uses in managing disorders involving abnormal fluid retention (edema) or in treating hypertension, in which their diuretic action causes decreased blood volume. Medical management of AC targeted toward heart failure.

Dosing

Adult

20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states

Pediatric

1-2 mg/kg/dose PO; not to exceed 6 mg/kg/dose; do not administer >q6h
1 mg/kg IV/IM slowly under close supervision; not to exceed 6 mg/kg

Interactions

Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently

Contraindications

Documented hypersensitivity; hepatic coma, anuria, and state of severe electrolyte depletion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Hydrochlorothiazide (Esidrix, HydroDIURIL, Microzide)

Inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water and potassium and hydrogen ions. Treatment may improve symptoms of venous congestion through elimination of retained fluid and preload reduction.

Dosing

Adult

25-100 mg PO qd or in divided doses; may administer qod

Pediatric

Not established

Interactions

May decrease effects of anticoagulants, antigout agents, and sulfonylureas; may increase toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, loop diuretics, lithium, diazoxide, digitalis, amphotericin B, and nondepolarizing muscle relaxants

Contraindications

Documented hypersensitivity; anuria or renal decompensation

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal disease, hepatic disease, gout, diabetes mellitus, and erythematosus

Spironolactone (Aldactone)

Potassium-sparing diuretic that nonselectively antagonizes aldosterone receptors.

Dosing

Adult

12.5-50 mg PO qd or in divided doses

Pediatric

Not established

Interactions

May potentiate hyperkalemia caused by ACE inhibitors, receptor blockers, and other drugs that may raise serum potassium levels; may increase levels of digoxin; effectiveness may be diminished by NSAIDS

Contraindications

Documented hypersensitivity; severe renal insufficiency; hyperkalemia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Liver dysfunction and impaired renal function

Eplerenone (Inspra)

Selectively blocks aldosterone at the mineralocorticoid receptors in epithelial tissues (eg, kidney) and nonepithelial tissues (eg, heart, blood vessels, brain); thus, decreases blood pressure and sodium reabsorption. Can be used in patients who are intolerant of spironolactone due to side effects of gynecomastia or menstrual irregularities.

Dosing

Adult

25-50 mg PO qd

Pediatric

Not established

Interactions

CYP450 3A4 substrate; potent CYP3A4 inhibitors (eg, ketoconazole) increase serum levels about 5-fold; less potent CYP3A4 inhibitors (eg, erythromycin, saquinavir, verapamil, fluconazole) increase serum levels about 2-fold; grapefruit juice increases serum levels about 25%; coadministration with potassium supplements, salt substitutes, or drugs known to increase serum potassium (eg, amiloride, spironolactone, triamterene, ACE inhibitors, angiotensin II inhibitors) increases risk of hyperkalemia

Contraindications

Documented hypersensitivity; renal (creatinine clearance <30) and liver impairment; preexisting hyperkalemia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause hyperkalemia, headache, and dizziness; caution with hepatic insufficiency

Electrolyte supplements

Help correct electrolyte abnormalities, including hypokalemia, hypomagnesemia, and hypophosphatemia.

Phosphate salts (Neutra-Phos-K)

IV preparations are available as sodium or potassium phosphate (K₂ PO₄). Response to IV serum phosphorus supplementation is highly variable and is associated with hyperphosphatemia and hypocalcemia. Infusion rate and initial dosage based on severity of hypophosphatemia and presence of symptoms.

Dosing

Adult

8 mmol q6h IV (32 mmol/d) initially
Aggressive IV replacement: 15 mmol over 6 h

Pediatric

0.25-0.5 mmol/kg IV over 4-6 h; repeat if symptomatic hypophosphatemia persists

Interactions

Magnesium- and aluminum-containing antacids or sucralfate can act as phosphate binders and decrease serum phosphate levels; potassium-sparing diuretics, ACE inhibitors, and salt substitutes may increase serum levels

Contraindications

Do not administer if patient diagnosed with hyperphosphatemia, hypocalcemia, hypomagnesemia, hyperkalemia, or renal failure

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with renal insufficiency or metabolic alkalosis; admixture of phosphate and calcium in IV fluids can result in calcium phosphate precipitation

Magnesium sulfate

Nutritional supplement in hyperalimentation; cofactor in enzyme systems involved in neurochemical transmission and muscular excitability. In adults, 60-180 mEq of potassium, 10-30 mEq of magnesium, and 10-40 mmol of phosphate per day may be necessary for optimum metabolic response.

Dosing

Adult

1 g IV/IM q6h for 4 doses up to 8-12 g/d in severe hypomagnesemia
Alternatively, 3 g PO q6h for 4 doses prn

Pediatric

25-50 mg/kg/dose IV/IM q4-6h for 3-4 doses

Interactions

Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade seen with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants and betamethasone and cardiotoxicity of ritodrine

Contraindications

Documented hypersensitivity; heart block, Addison disease, myocardial damage, or severe hepatitis

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Magnesium may alter cardiac conduction, leading to heart block in digitalized patients; monitor respiratory rate, deep tendon reflex, and renal function when electrolyte is administered parenterally; caution when administering magnesium dose because may produce significant hypotension or asystole; in overdose, calcium gluconate, 10-20 mL IV of 10% solution, can be given as antidote for clinically significant hypermagnesemia

Potassium chloride (Cena-K, Kaochlor, K-Dur, Klor-Con)

Essential for transmission of nerve impulses, contraction of cardiac muscle, maintenance of intracellular tonicity, skeletal and smooth muscles, and maintenance of normal renal function. Gradual depletion occurs via renal excretion, through GI loss, or because of low intake.
Depletion usually results from diuretic therapy, primary or secondary hyperaldosteronism, diabetic ketoacidosis, severe diarrhea, if associated with vomiting, or inadequate replacement during prolonged parenteral nutrition.
Potassium depletion sufficient to cause 1 mEq/L drop in serum potassium requires a loss of approximately 100-200 mEq from total body store.

Dosing

Adult

Serum levels >2.5 mEq/L: 10 mEq IV over 1 h and prn based on frequently obtained lab values; not to exceed 200 mEq/24h
Serum levels <2.5 mEq/L: 40 mEq IV over 1 h and prn based on frequently obtained lab values; not to exceed 400 mEq/24h

Pediatric

Initially, administer 1 mEq/kg IV over 1-2 h and prn based on frequently obtained lab values

Interactions

Concurrent use with ACE inhibitors may result in elevated serum potassium concentrations; potassium-sparing diuretics and potassium-containing salt substitutes can produce severe hyperkalemia; in patients taking digoxin, hypokalemia may result in digoxin toxicity; caution if discontinuing potassium administration in patients maintained on digoxin

Contraindications

Hyperkalemia, renal failure, conditions in which potassium retention is present, oliguria or azotemia, crush syndrome, severe hemolytic reactions, anuria, and adrenocortical insufficiency

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Do not infuse rapidly; high plasma concentrations may cause death due to cardiac depression, arrhythmias, or arrest; plasma levels do not necessarily reflect tissue levels; monitor replacement therapy whenever possible by performing continuous or serial ECG; when a concentration >40 mEq/L is infused, local pain and phlebitis may also follow

Follow-up

Prognosis

• 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 and, 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 dilated cardiomyopathy (DC).
  • Nakanishi et al identified 11 patients with AC and reported significant improvement in 8 patients who abstained from alcohol use and marked worsening in the 3 patients who continued to abuse alcohol, including death from heart failure in 2 patients.¹⁰
  • A 12-month observation study of 20 patients with AC reported abstinence in 10 patients and noted smaller cavity diameters, better clinical evaluation findings, and fewer hospitalizations in the patients who abstained.
  • Guillo and colleagues evaluated 14 patients with AC over a 3-year period with serial examinations, 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 one 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.¹¹
  • 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 left ventricular ejection fraction. Ten patients who continued to drink higher amounts of alcohol all died during the follow-up period.
• In 1974, Demakis and colleagues completed what is perhaps the largest evaluation of the natural history of AC. They 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. Overall, the 2 factors that were associated with a better prognosis were abstinence and a shorter duration of symptoms before the initiation of therapy.¹²
• Several studies have compared the natural history of AC with that of DC.
  • In 1996, Prazak et al conducted a retrospective study comparing 23 patients with AC to 52 patients with idiopathic DC. The 2 groups had similar ejection fractions, New York Heart Association class symptoms, and overall LV volume. The sole endpoint was all-cause mortality. The 1-, 5-, and 10-year survival rates for AC were 100%, 81%, and 81%, respectively, compared to 89%, 48%, and 30%, respectively for idiopathic DC. When transplant-free survival was compared, the difference was more impressive, with 10-year survival rates of 81% and 20%, respectively.¹³
  • This is in contrast to a 1993 study by Redfield et al that showed no difference in mortality between patients with AC and patients with idiopathic DC.¹⁴
  • Prazak et al speculate that the difference may be due to more complete abstinence and aggressive medical therapy in the patients in their study.¹³

Patient Education

• For excellent patient education resources, visit eMedicine's Mental Health and Behavior Center and Substance Abuse Center. Also, see eMedicine's patient education articles Alcoholism, Alcohol Intoxication, Drug Dependence and Abuse, and Substance Abuse.

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Keywords

alcoholism, alcohol consumption, alcohol abuse, ethanol consumption, ethanol abuse, ethanol toxicity, alcohol toxicity, cardiovascular disease, CVD, cardiac enlargement, cardiac failure, heart failure, alcoholic cardiomyopathy, AC, arrhythmia, atrial fibrillation, atrial flutter, supraventricular arrhythmia, premature ventricular contractions, sudden death, hypertension, stroke, dilated cardiomyopathy, DC, acute ethanol-induced injury, beriberi heart disease, thiamine deficiency, acetaldehyde, myocarditis

Contributor Information and Disclosures

Author

Eric D Popjes, MD, Assistant Professor, Department of Medicine, Division of Cardiology, Penn State Milton S Hershey Medical Center
Eric D Popjes, MD is a member of the following medical societies: American College of Cardiology, Heart Failure Society of America, and International Society for Heart and Lung Transplantation
Disclosure: Nothing to disclose.

Coauthor(s)

Frank E Silvestry, MD, Director, PENN Cardiac Care at Radnor; Assistant Professor, Department of Medicine, Division of Cardiovascular Disease, University of Pennsylvania Health System
Frank E Silvestry, MD is a member of the following medical societies: American College of Cardiology, American Medical Association, and American Society of Echocardiography
Disclosure: Nothing to disclose.

Medical Editor

Gary E Sander, MD, PhD, Professor, Department of Internal Medicine, Division of Cardiology, Tulane University Health Sciences Center
Gary E Sander, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Hypertension, Heart Failure Society of America, Louisiana State Medical Society, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Frank M Sheridan, MD, Cardiology, Providence Everett Medical Center
Frank M Sheridan, MD is a member of the following medical societies: American College of Cardiology, American Heart Association, and Society for Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

CME Editor

Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital
Amer Suleman, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Institute of Stress, American Society of Hypertension, Federation of American Societies for Experimental Biology, Royal Society of Medicine, and Society of Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

Chief Editor

Patrice Delafontaine, MD, FACC, FAHA, FACP, FESC, Sidney W and Marilyn S Lassen Professor of Cardiovascular Medicine, Chief, Section of Cardiology, Director, Cardiovascular Center of Excellence, Tulane University; Professor of Physiology, Chair, Department of Medicine, Tulane University School of Medicine
Patrice Delafontaine, MD, FACC, FAHA, FACP, FESC is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American College of Cardiology, American College of Physicians, American Diabetes Association, American Federation for Clinical Research, American Federation for Medical Research, American Heart Association, American Medical Association, American Society for Clinical Investigation, Association of American Physicians, Association of Professors of Cardiology, Association of Professors of Medicine, Endocrine Society, European Society of Cardiology, Louisiana State Medical Society, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

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