Impaired Relaxation of the Heart

7/29/2019 Impaired Relaxation of the Heart

1/28

1. about us

2. mycme login3. contact us

4. faq

Search

All documents

Home Medical Publications Disease Management Project Cardiology

SECTION INDEXo Allergy & Immunologyo Cardiologyo Dermatologyo Endocrinologyo Gastroenterology
http://www.clevelandclinicmeded.com/welcome.htmhttp://www.clevelandclinicmeded.com/welcome.htmhttp://www.clevelandclinicmeded.com/mycme/mylogin.asphttp://www.clevelandclinicmeded.com/mycme/mylogin.asphttp://www.clevelandclinicmeded.com/info.htmhttp://www.clevelandclinicmeded.com/info.htmhttp://www.clevelandclinicmeded.com/faqs.htmhttp://www.clevelandclinicmeded.com/faqs.htmhttp://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/medicalpubshttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagementhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiologyhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/dermatology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/dermatology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/http://www.clevelandclinicmeded.com/live/courses/cardioreview/overview.asp?utm_source=Web_Marketing&utm_medium=house-ad&utm_content=CARDIO-HeartFail-Cardio&utm_campaign=13DMPhttp://www.clevelandclinicmeded.com/partners/http://www.clevelandclinicmeded.com/medicalpubs/http://www.clevelandclinicmeded.com/online/webcast/http://www.clevelandclinicmeded.com/online/text-based.aspxhttp://www.clevelandclinicmeded.com/live/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/live/courses/cardioreview/overview.asp?utm_source=Web_Marketing&utm_medium=house-ad&utm_content=CARDIO-HeartFail-Cardio&utm_campaign=13DMPhttp://www.clevelandclinicmeded.com/partners/http://www.clevelandclinicmeded.com/medicalpubs/http://www.clevelandclinicmeded.com/online/webcast/http://www.clevelandclinicmeded.com/online/text-based.aspxhttp://www.clevelandclinicmeded.com/live/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/live/courses/cardioreview/overview.asp?utm_source=Web_Marketing&utm_medium=house-ad&utm_content=CARDIO-HeartFail-Cardio&utm_campaign=13DMPhttp://www.clevelandclinicmeded.com/partners/http://www.clevelandclinicmeded.com/medicalpubs/http://www.clevelandclinicmeded.com/online/webcast/http://www.clevelandclinicmeded.com/online/text-based.aspxhttp://www.clevelandclinicmeded.com/live/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/live/courses/cardioreview/overview.asp?utm_source=Web_Marketing&utm_medium=house-ad&utm_content=CARDIO-HeartFail-Cardio&utm_campaign=13DMPhttp://www.clevelandclinicmeded.com/partners/http://www.clevelandclinicmeded.com/medicalpubs/http://www.clevelandclinicmeded.com/online/webcast/http://www.clevelandclinicmeded.com/online/text-based.aspxhttp://www.clevelandclinicmeded.com/live/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/live/courses/cardioreview/overview.asp?utm_source=Web_Marketing&utm_medium=house-ad&utm_content=CARDIO-HeartFail-Cardio&utm_campaign=13DMPhttp://www.clevelandclinicmeded.com/partners/http://www.clevelandclinicmeded.com/medicalpubs/http://www.clevelandclinicmeded.com/online/webcast/http://www.clevelandclinicmeded.com/online/text-based.aspxhttp://www.clevelandclinicmeded.com/live/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/live/courses/cardioreview/overview.asp?utm_source=Web_Marketing&utm_medium=house-ad&utm_content=CARDIO-HeartFail-Cardio&utm_campaign=13DMPhttp://www.clevelandclinicmeded.com/partners/http://www.clevelandclinicmeded.com/medicalpubs/http://www.clevelandclinicmeded.com/online/webcast/http://www.clevelandclinicmeded.com/online/text-based.aspxhttp://www.clevelandclinicmeded.com/live/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/live/courses/cardioreview/overview.asp?utm_source=Web_Marketing&utm_medium=house-ad&utm_content=CARDIO-HeartFail-Cardio&utm_campaign=13DMPhttp://www.clevelandclinicmeded.com/partners/http://www.clevelandclinicmeded.com/medicalpubs/http://www.clevelandclinicmeded.com/online/webcast/http://www.clevelandclinicmeded.com/online/text-based.aspxhttp://www.clevelandclinicmeded.com/live/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/live/courses/cardioreview/overview.asp?utm_source=Web_Marketing&utm_medium=house-ad&utm_content=CARDIO-HeartFail-Cardio&utm_campaign=13DMPhttp://www.clevelandclinicmeded.com/partners/http://www.clevelandclinicmeded.com/medicalpubs/http://www.clevelandclinicmeded.com/online/webcast/http://www.clevelandclinicmeded.com/online/text-based.aspxhttp://www.clevelandclinicmeded.com/live/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/live/courses/cardioreview/overview.asp?utm_source=Web_Marketing&utm_medium=house-ad&utm_content=CARDIO-HeartFail-Cardio&utm_campaign=13DMPhttp://www.clevelandclinicmeded.com/partners/http://www.clevelandclinicmeded.com/medicalpubs/http://www.clevelandclinicmeded.com/online/webcast/http://www.clevelandclinicmeded.com/online/text-based.aspxhttp://www.clevelandclinicmeded.com/live/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/gastroenterology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/dermatology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiologyhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagementhttp://www.clevelandclinicmeded.com/medicalpubshttp://www.clevelandclinicmeded.com/http://www.clevelandclinicmeded.com/faqs.htmhttp://www.clevelandclinicmeded.com/info.htmhttp://www.clevelandclinicmeded.com/mycme/mylogin.asphttp://www.clevelandclinicmeded.com/welcome.htm


2/28

o Hematology & Oncologyo Hepatologyo Infectious Diseaseo Nephrologyo Neurologyo Preventive Medicineo Psychiatry & Psychologyo Pulmonary Diseaseo Rheumatologyo Women's Health

DISEASE MANAGEMENT PROJECT MAINo Chapter Indexo Editorial Boardo Editorial Policy

Text-based CME caseso Disease Management Project Clinical Decisions

Published: August 2010

Heart FailureRobert Hobbs

Andrew Boyle

CHAPTER SECTION LINKS

Definition and etiology

Prevalence and risk factors

Pathophysiology and natural history

Signs and symptoms

Diagnosis

Treatment

Prevention and screening

Considerations in special populations

Summary

References

Definition and etiology
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hematology-oncology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hematology-oncology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/nephrology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/nephrology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/preventive-medicine/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/preventive-medicine/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/psychiatry-psychology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/psychiatry-psychology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/pulmonary/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/pulmonary/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/rheumatology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/rheumatology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/womens-health/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/womens-health/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/editorialboard.htmhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/editorialboard.htmhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/editorialpolicy.htmhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/editorialpolicy.htmhttp://www.clevelandclinicmeded.com/online/casebased/decisionmaking/http://www.clevelandclinicmeded.com/online/casebased/decisionmaking/http://my.clevelandclinic.org/staff_directory/physician_name_search.aspx#327http://my.clevelandclinic.org/staff_directory/physician_name_search.aspx#17563http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0025http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0030http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0035http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0160http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0165http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#cesummaryhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#referenceshttp://window.print%28%29/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#referenceshttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#cesummaryhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0165http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0160http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0035http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0030http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0025http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#s0010http://my.clevelandclinic.org/staff_directory/physician_name_search.aspx#17563http://my.clevelandclinic.org/staff_directory/physician_name_search.aspx#327http://www.clevelandclinicmeded.com/online/casebased/decisionmaking/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/editorialpolicy.htmhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/editorialboard.htmhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/womens-health/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/rheumatology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/pulmonary/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/psychiatry-psychology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/preventive-medicine/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/nephrology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hematology-oncology/


3/28

Heart failure is a clinical syndrome characterized by systemic perfusion inadequate to meet the body's metabolic

demands as a result of impaired cardiac pump function. This may be further subdivided into systolic or diastolic heart

failure. In systolic heart failure, there is reduced cardiac contractility, whereas in diastolic heart failure there is

impaired cardiac relaxation and abnormal ventricular filling (Fig. 1).

Figure 1: Click to Enlarge

The most common cause of heart failure is left ventricular (LV) systolic dysfunction (about 60% of patients). In this

category, most cases are a result of end-stage coronary artery disease, either with a history of myocardial infarction

or with a chronically underperfused, yet viable, myocardium. In many patients, both processes are present

simultaneously (Fig. 2A). Other common causes of LV systolic dysfunction include idiopathic dilated cardiomyopathy,

valvular heart disease, hypertensive heart disease, toxin-induced cardiomyopathies (e.g., doxorubicin, herceptin,

alcohol), and congenital heart disease (seeFig. 2B).


Right ventricular systolic dysfunction is usually a consequence of LV systolic dysfunction. It can also develop as a

result of right ventricular infarction, pulmonary hypertension, chronic severe tricuspid regurgitation, or arrhythmogenic

right ventricular dysplasia. A less-common cause of heart failure is high-output failure caused by thyrotoxicosis,

arteriovenous fistulae, Paget's disease, pregnancy, or severe chronic anemia.

Diastolic LV dysfunction (impaired relaxation) usually is related to chronic hypertension or ischemic heart disease.

Other causes include restrictive, infiltrative, and hypertrophic cardiomyopathies. Inadequate filling of the right ventricle

can result from pericardial constriction or cardiac tamponade.

Back to Top

Prevalence and risk factors
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig1_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig2_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig2_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig1_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig2_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig1_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig2_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig1_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0010


4/28

Heart failure is a common syndrome, especially in older adults. Although more patients survive acute myocardial

infarction because of reperfusion therapy, most have at least some residual LV systolic dysfunction, which can lead to

heart failure. Currently, 5 million Americans are afflicted with heart failure, approximately 2% of the

population.1Patients with heart failure account for about 1 million hospital admissions annually, and another 2 million

patients have heart failure as a secondary diagnosis. One third of these patients are readmitted within 90 days for

recurrent decompensation.

Patients at high risk for developing heart failure are those with hypertension, coronary artery disease, diabetes

mellitus, family history of cardiomyopathy, use of cardiotoxins, and obesity.

Back to Top

Pathophysiology and natural history

Although much progress has been made in the treatment of heart failure, there is a high overall annual mortality (5%-

20%), particularly in patients with New York Heart Association (NYHA) Class IV symptoms.2Many patients succumb

to progressive pump failure and congestion, although one half die from sudden cardiac death. Some patients die from

end-organ failure resulting from inadequate systemic organ perfusion, particularly to the kidneys. Indicators of poor

cardiac prognosis include renal dysfunction, cachexia, valvular regurgitation, ventricular arrhythmias, higher NYHA

heart failure class, lower LV ejection fraction (LVEF), high catecholamine and B-type natriuretic peptide (BNP) levels,

low serum sodium level, hypocholesterolemia, and marked LV dilation. Patients with combined systolic and diastolic

LV dysfunction also have a worse prognosis than patients with either in isolation.3

In LV systolic dysfunction, the body activates several neurohormonal pathways to increase circulating blood volume.

The sympathetic nervous system increases heart rate and contractility, causes arteriolar vasoconstriction in

nonessential vascular beds, and stimulates secretion of renin from the juxtaglomerular apparatus of the kidney.

Unfortunately, catecholamines aggravate ischemia, potentiate arrhythmias, promote cardiac remodeling, and are

directly toxic to myocytes. Stimulation of the renin-angiotensin system as a result of increased sympathetic

stimulation and decreased renal perfusion results in further arteriolar vasoconstriction, sodium and water retention,

and release of aldosterone. An increased aldosterone level, in turn, leads to sodium and water retention, endothelial

dysfunction, and organ fibrosis.

In heart failure, baroreceptor and osmotic stimuli lead to vasopressin release from the hypothalamus, causing

reabsorption of water in the renal collecting duct. Although these neurohormonal pathways initially are compensatory
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib1http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib1http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib2http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib2http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib2http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib3http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib3http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib3http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib3http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib2http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib1


5/28

and beneficial, eventually they are deleterious, and neurohormonal modulation is the basis for modern treatment of

heart failure.

In contrast, natriuretic peptides are hormones released by secretory granules in cardiac myocytes in response to

myocardial stretching. They have a beneficial influence in heart failure, including systemic and pulmonary

vasodilation, possible enhancement of sodium and water excretion, and suppression of other neurohormones.

With continuous neurohormonal stimulation, the left ventricle undergoes remodeling consisting of LV dilation and

hypertrophy, such that stroke volume is increased without an actual increase in EF. This is achieved by myocyte

hypertrophy and elongation. LV chamber dilation causes increased wall tension, worsens subendocardial myocardial

perfusion, and can provoke ischemia in patients with coronary atherosclerosis. Furthermore, dilation of the LV

chamber can cause mitral annular dilatation and mitral regurgitation, leading to pulmonary congestion.

In diastolic dysfunction, the primary abnormality is impaired LV relaxation, causing high diastolic pressures and poor

filling of the ventricle. To increase diastolic filling, left atrial and pulmonary capillary pressures increase and

pulmonary edema ensues. As a result, patients are often symptomatic with exertion when increased heart rate

reduces LV filling time and circulating catecholamines worsen diastolic dysfunction.++

-

+-*

The American College of Cardiology (ACC) and American Heart Association (AHA) have developed a classification of

heart failure based on stages of the syndrome (Table 1).4Stage A includes patients who are at risk for developing

heart failure but who have no structural heart disease at present. The management strategy in this group is

prevention of heart failure. Stage B includes patients with structural heart disease but no symptoms. The

management goal is prevention of LV remodeling leading to heart failure. Stage C includes patients with structural

heart disease with current or prior symptomatic heart failure. Diuretics, digoxin, and aldosterone antagonists may be

added to angiotensin-converting enzyme (ACE)
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib4http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib4http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib4http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib4http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0010


6/28


7/28


8/28

inhibitors and beta blockers, depending on the severity of symptoms. Cardiac resynchronization therapy also may be

considered. Stage D includes patients with severe refractory heart failure. Physicians should consider either end-of-

life care or high-technology therapies such as cardiac transplantation or mechanical circulatory support, based on

individual cases.

Table 1: American College of CardiologyAmerican Heart Association Classification of ChronicHeart Failure

Stage Description

A****++ Hypertension, diabetes mellitus, CAD, family history of cardiomyopathy


9/28


10/28

: High risk for developing heart failure

B: Asymptomatic heart failure Previous MI, LV dysfunction, valvular heart disease

C: Symptomatic heart failure Structural heart disease, dyspnea and fatigue, impaired exercise tolerance

D: Refractory end-stage heart failure Marked symptoms at rest despite maximal medical therapy

CAD, coronary artery disease; LV, left ventricular; MI, myocardial infarction.

Back to Top

Signs and symptoms

There is a wide spectrum of potential clinical manifestations of heart failure.5Most patients have signs and symptoms

of fluid overload and pulmonary congestion, including dyspnea, orthopnea, and paroxysmal nocturnal dyspnea.

Patients with right ventricular failure have jugular venous distention, peripheral edema, hepatosplenomegaly, and

ascites. Others, however, do not have congestive symptoms but have signs and symptoms of low cardiac output,

including fatigue, effort intolerance, cachexia, and renal hypoperfusion. The NYHA functional classification scheme is

used to assess the severity of functional limitations and correlates fairly well with prognosis (Table 2).

Table 2: New York Heart Association (NYHA) Heart Failure Symptom Classification System

NYHA

ClassLevel of Impairment

I No symptom limitation with ordinary physical activity

II Ordinary physical activity somewhat limited by dyspnea (e.g., long-distance walking, climbing two

flights of stairs)

III Exercise limited by dyspnea with moderate workload (e.g., short-distance walking, climbing one flight

of stairs)

IV Dyspnea at rest or with very little exertion

On physical examination, patients with decompensated heart failure may be tachycardic and tachypneic, with bilateral

inspiratory rales, jugular venous distention, and edema. They often are pale and diaphoretic. The first heart sound

usually is relatively soft if the patient is not tachycardic. An S3 and often an S4 gallop will be present. Murmurs of
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib5http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib5http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib5http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib5http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#top


11/28

mitral or tricuspid regurgitation may be heard. Paradoxical splitting of S2 may be present because of delayed

mechanical or electrical activation of the left ventricle. Patients with compensated heart failure will likely have clear

lungs but a displaced cardiac apex. Patients with decompensated diastolic dysfunction usually have a loud S4(which

may be palpable), rales, and often systemic hypertension.

Back to Top

Diagnosis

The initial evaluation of new-onset heart failure should include an electrocardiogram, chest radiograph, and BNP

assay. EK6 findings of LV hypertrophy, left bundle branch block, intraventricular conduction delay, and nonspecific

ST-segment and T wave changes support a diagnosis of heart failure. Q waves in contiguous leads strongly implicate

a previous myocardial infarction and coronary atherosclerosis as the cause. Chest radiographic findings of heart

failure include cardiomegaly, pulmonary vascular redistribution, pulmonary venous congestion, Kerley B lines,

alveolar edema, and pleural effusions.

The single most useful diagnostic test is the echocardiogram, which can distinguish between systolic and diastolic

dysfunction. If systolic dysfunction is present, regional wall motion abnormalities or LV aneurysm suggest an ischemic

basis for heart failure, whereas global dysfunction suggests a nonischemic cause. Echocardiography is helpful in

determining other causes, such as valvular heart disease, cardiac tamponade, or pericardial constriction, and

provides useful clues about infiltrative and restrictive cardiomyopathies. Echocardiography can also provide

meaningful prognostic information about diastolic function, severity of hypertrophy, chamber size, and valvular

abnormalities. In many cases, however, the exact cause of the heart failure cannot be discerned from the

echocardiogram.

Cardiac catheterization can detect coronary atherosclerosis as the cause of heart failure. Severe coronary artery

disease is so prevalent that coronary angiography routinely should be performed to exclude this cause and, if found,

should lead to an assessment of myocardial viability, with a goal of revascularization. Coronary computed

tomographic angiography (CTA) might also be a suitable alternative to exclude coronary artery disease in select

patients.

Magnetic resonance imaging (MRI) is useful in assessing for arrhythmogenic right ventricular dysplasia, myocardial

viability, and infiltrative cardiomyopathies.

Objective information about functional capacity can be obtained from metabolic (cardiopulmonary) exercise testing.

This test can distinguish ventilatory from cardiac limitations in patients with exertional dyspnea. A peak oxygen
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#top


12/28

consumption higher than 25 mL/kg/min is normal for middle-age adults, but a value lower than 14 mL/kg/min

indicates severe cardiac limitation and poor prognosis.

A useful diagnostic test for the detection of heart failure is the BNP assay.6, 7

BNP levels correlate with severity of

heart failure and decrease as a patient reaches a compensated state. This blood test may be useful for distinguishing

heart failure from pulmonary disease. Because smokers often have both these clinical diagnoses, differentiating

between them may be challenging.

The routine use of invasive hemodynamic monitoring to guide the management of decompensated heart failure has

not proved to be beneficial. However, invasive hemodynamic monitoring may be warranted if unanticipated

responses to therapies are observed or for diagnostic purposes if the diagnosis is uncertain.

Back to Top

Summary

Jugular venous distention is a useful physical sign of heart failure.

The lungs usually are clear in chronic heart failure.

The BNP assay improves the accuracy of diagnosing heart failure.

Echocardiography is the single most useful diagnostic modality.

Coronary angiography confirms or excludes coronary artery disease as the cause.

Back to Top

Treatment

Lifestyle Modifications

Dietary sodium and fluid restrictions should be implemented in all patients with congestive heart failure. Limiting

patients to 2 g/day of dietary sodium and 2 L/day of fluid will lessen congestion and decrease the need for diuretics.

Patient education guidelines are listed in Box 1.

Box 1: Patient Education Guidelines

2-g Sodium diet

Monitoring weight daily

2-L Fluid restriction
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib6http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib6http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib6http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#b0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#b0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib6


13/28

Monitoring blood pressure

Medications

Smoking cessation

Light aerobic exercise

Knowing whom to call

Achieving ideal weight

Follow-up visits

Cardiac rehabilitation can improve symptoms and exercise tolerance in patients with heart failure. This will also

reduce or prevent skeletal muscle atrophy that could worsen exercise tolerance. Weight loss is encouraged in obese

patients. Patients should be counseled about smoking cessation.

Medical OptionsAngiotensin-Convert ing Enzyme Inhib i tors

All patients with LV systolic dysfunction should be treated with an ACE inhibitor unless they have a contraindication or

intolerance to the drug (stages B to D). ACE inhibitors are useful in preventing heart failure in patients at high risk

who have atherosclerotic cardiovascular disease, diabetes mellitus, or hypertension with associated cardiovascular

risk factors (stage A). ACE inhibitors and beta blockers should be used for all patients with a history of myocardial

infarction, regardless of LVEF. Vasodilation and neurohormonal modulation with ACE inhibitors improve mortality,

heart failure symptoms, exercise tolerance, and LVEF as well as reduce emergency room visits and

hospitalizations.8-10

The dose of ACE inhibitors should be titrated to the maximum tolerated dose11

or the target dose as listed in Table 3.

Approximately 10% to 20% of patients do not tolerate ACE inhibitors. The main side effect from ACE inhibition is a

dry hacking cough, which can necessitate change to an angiotensin II receptor blocker (ARB). Most patients who

cough on ACE inhibitors have this symptom because of congestive heart failure rather than ACE inhibitor intolerance

and might improve with further diuresis. Two uncommon side effects of ACE inhibitors are angioedema and acute

renal failure (caused by bilateral renal artery stenosis); both necessitate immediate cessation of the drug.

Table 3: Angiotensin-Converting Enzyme Inhibitor Dosing

Agent Target Dose (mg) Frequency
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib8http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib8http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib8http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib11http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib11http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib11http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib8


14/28

Captopril* 50 tid

Enalapril* 20 bid

Lisinopril* 40 qd

Ramipril* 5 bid

Quinapril* 20 bid

Fosinopril* 20 bid

Benazepril* 20 qd

Trandolapril 4 qd

*FDA-approved for treatment of heart failure.

FDA-approved for treatment of postmyocardial infarction heart failure.

ACE inhibitors should be used in combination with beta blockers in most patients. Either agent may be started first.

Angiotensin Receptor Blockers

ARBs block the effects of angiotensin II at the receptor level (Table 4). In clinical trials, these agents were found to be

superior to placebo but no better than ACE inhibitors in improving mortality.12

ARBs are recommended as second-line

therapy in patients who do not tolerate ACE inhibitors because of cough or angioedema (stages B to D). ARBs should

not be substituted for ACE inhibitors in cases of hyperkalemia or renal dysfunction. ARBs may have morbidity

benefits for patients with diastolic heart failure.13

Table 4: Angiotensin Receptor Blocker Dosing

Agent Initial Dose (mg) Maximum Dose (mg)

Valsartan* 80 320

Candesartan* 4 32

Losartan 25 100

Irbesartan 75 300

Telmisartan 40 80

Eprosartan 400 800

Olmesartan 20 40
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0025http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib12http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib12http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib12http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib13http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib13http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib13http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib13http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib12http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0025http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tn0010


15/28

*FDA-approved for treatment of heart failure.

Beta Blockers

Three beta blockerscarvedilol, metoprolol succinate (Toprol XL), and bisoprololhave been shown to improve

survival in patients with heart failure (Table 5).14-16

Metoprolol tartrate is not U.S Food and Drug Administration (FDA)-

approved for heart failure and was less effective than carvedilol in preventing sudden death.17

The exact mechanism

of beta blocker action is unclear, but it likely involves antiarrhythmic, anti-ischemic, antiremodeling, and antiapoptotic

properties, as well as improved beta receptor pathway function. Myocardial oxygen consumption is reduced wi th beta

blockers, primarily because of a reduction in heart rate.

Table 5: Beta Blocker Dosing

Beta Blocker Initial Dose (mg) Target Dose

Carvedilol* 3.125 mg bid 50 mg bid if >75 kg

25 mg bid if


16/28

should be prescribed to most patients. Digoxin may be prescribed for patients with LV systolic dysfunction who

remain symptomatic while receiving standard medical therapy, particularly if they are in atrial fibrillation.

Table 6: Other Heart Failure Drugs

Agent Initial DoseMaximum

DoseGuidelines

Digoxin 0.125 mg

qd

0.25 mg qd Reduce dose in women with renal dysfunction, with amiodarone

Hydralazine 25 mg qid 100 mg qid Use concurrently with nitrates to prevent coronary steal

Isosorbide

dinitrate

20 mg tid 80 mg tid Also useful for angina pectoris

Spironolactone 25 mg qd 50 mg qd Weak diuretic, risk of hyperkalemia, avoid in renal dysfunction;

gynecomastia

Eplerenone 25 mg qd 50 mg qd Risk of hyperkalemia, avoid in renal dysfunction; no

gynecomastia

Diuretics

Diuretics should be used in combination with an ACE inhibitor (or ARB) and a beta blocker. Most patients with heart

failure have some degree of symptomatic congestion and benefit from diuretic therapy.19

Usually, a loop diuretic is

required, with the addition of a thiazide diuretic in patients refractory to the loop diuretic alone (diuretic resistance or

cardiorenal syndrome). Although useful for symptomatic relief, diuretics have not been shown to improve survival,

and they can cause azotemia, hypokalemia, metabolic alkalosis, and elevation of neurohormone levels (Table 7).

Table 7: Diuretic Dosing

Generic Name ClassInitial Dose

(mg)Special Considerations

Furosemide Loop 20 Can be given intravenously; PO equivalent is twice the IV dose

Bumetanide Loop 0.5 Good oral bioavailability; can be given intravenously; oral and IV

doses are the same

Torsemide Loop 5-10 Best oral availability

Ethacrynic acid Loop 50 Only diuretic with no sulfhydryl group; used if allergic to furosemide
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib19http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib19http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib19http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0040http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0040http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib19


17/28

Hydrochlorothiazide Thiazide 12.5 Weak diuretic; used mainly for hypertension

Metolazone Thiazide 2.5 Give1/2 hr before furosemide; only available orally; high risk of

hypokalemia

Aldosterone Antagonists

Two aldosterone antagonists have been approved for patients with heart failure: spironolactone and eplerenone. A

30% reduction in mortality and hospitalizations has been reported when spironolactone is added to standard therapy

for patients with NYHA Class III or IV heart failure and a serum creatinine less than 2.5.20

A 15% reduction in the risk

of death and hospitalization has been reported in patients who had heart failure and an LVEF lower than 40% after a

myocardial infarction and who were treated with eplerenone.21

Aldosterone inhibition can prevent sodium and water retention, endothelial dysfunction, and myocardial fibrosis. With

aldosterone antagonists, diligent monitoring of serum potassium levels is mandatory, because patients can develop

hyperkalemia (see Table 6). These drugs should be avoided in patients with a creatinine level higher than 2.5 mg/dL.

Eight percent of men develop gynecomastia with spironolactone but not with eplerenone. Data from studies of mild

heart failure are lacking, and so these drugs should be reserved for patients with moderately severe to severe heart

failure. Therefore, the addition of an aldosterone antagonist is reasonable for select patients with moderately severe

to severe symptoms of heart failure and reduced LVEF who can be carefully monitored for preserved renal function

and normal potassium concentration.

Hydralazine and Nitrates

Hydralazine is an arterial dilator and nitrates are venous dilators. Hydralazine also prevents nitrate tachyphylaxis

(loss of effect). The combination of hydralazine and nitrate is inferior to an ACE inhibitor in improving survival.22

Once-

daily dosing of ACE inhibitors is easier than giving nitrates three times daily and giving hydralazine four times daily

(see Table 6). The combination of hydralazine and nitrate is reasonable for patients who have current or prior

symptoms of heart failure and reduced LVEF and who cannot be given an ACE or ARB because of drug intolerance,

hyperkalemia, or renal insufficiency. Hydralazine and nitrate also may be added to ACE inhibitors and beta blockers

when additional afterload reduction is needed or pulmonary hypertension is present. A fixed-dose combination tablet

has been approved for treating heart failure in African Americans.

Other Medical Therapies

Patients with known coronary artery disease should be treated with aspirin and a statin to lower the low-density

lipoprotein (LDL) level to 70 mg/dL. Calcium channel antagonists have not been proved beneficial in heart failure
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib20http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib20http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib20http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib21http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib21http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib21http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0035http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib22http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib22http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0035http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0035http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib22http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0035http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib21http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib20


18/28

patients. Dihydropyridines such as amlodipine have a neutral effect on heart failure and may be useful for treating

concomitant hypertension or angina pectoris.23

The use of warfarin to prevent cardioembolic strokes remains controversial in the absence of atrial arrhythmias,

because the risk appears to be relatively low (1%-3% per year). Warfarin therapy is recommended for patients with

atrial arrhythmias, previous embolic event, cardiac thrombi, or LV aneurysms.

Specific therapies for treating atrial fibrillation, sleep apnea, anemia, obesity, and thyroid disease may improve the

symptoms and functional limitations of heart failure.

Intravenous Inotropes and VasodilatorsDobutamine

Dobutamine (Table 8) enhances contractility by directly stimulating cardiac 1 receptors.24

Intravenous (IV)

dobutamine infusions, sometimes guided by hemodynamic monitoring, may be useful for select patients with acute

hypotensive heart failure or shock. The dose of dobutamine should always be titrated to the lowest dose compatible

with hemodynamic stability to minimize adverse events. As with many inotropes, long-term infusions of dobutamine

can increase mortality, principally because of its arrhythmogenic effect. As a result, chronic dobutamine infusions are

reserved for palliative symptom relief or for patients who have an implantable cardioverter-defibrillator (ICD) and are

awaiting heart transplantation. Intermittent outpatient infusions of dobutamine are not recommended for routine

management of heart failure.

Table 8: Intravenous Agents Used for Treatment of Heart Failure

Drug Dose Special Considerations

Dobutamine 2-20 g/kg/min receptor agonist; proarrhythmic; heart rate; ischemia

Milrinone 0.25-0.75 g/kg/min Phosphodiesterase inhibitor; vasodilator; may improve pulmonary

hypertension; used for patients taking beta blockers; proarrhythmic

Nitroglycerin 10-500 g/min Anti-ischemic; vasodilator; limited by vascular headache; hypotension,

tolerance develops rapidly

Nitroprusside 10-500 g/min Thiocyanate accumulation in renal failure; may provoke ischemia by

coronary steal; vasodilator; should be given only in intensive care unit

Nesiritide 2-g/kg bolus; then

0.01 g/kg/min

Fixed weight-based dose; vasodilator; occasional hypotension

Mil r inone
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib23http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib23http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib23http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib24http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib24http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib24http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib24http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib23


19/28

Milrinone (see Table 8) is a phosphodiesterase inhibitor that enhances contractility. Milrinone is useful for patients

with low-output heart failure and pulmonary hypertension because it is a more potent pulmonary vasodilator than

dobutamine. Milrinone, in contrast to dobutamine, is also useful for patients on chronic oral beta blocker therapy who

develop acute heart failure. The OPTIME (Outcomes of a Prospective Trial of Intravenous Milrinone for

Exacerbations of Chronic Heart Failure) study, involving the routine intravenous infusion of milrinone for 48 hours

during hospitalization for decompensated heart failure, failed to show clinical benefit and was associated with an

increased risk of atrial arrhythmias and hypotension.25

Similar to dobutamine, intermittent outpatient milrinone

infusions are not recommended for routine management of heart failure.

Nitroglycerin

Nitroglycerin (see Table 8) is a nitric oxide donor that causes vasodilation. It is a venodilator at low doses and an

arterial dilator at higher doses, lowering intracardiac pressures and alleviating pulmonary congestion.

Nitroglycerin also dilates coronary arteries, making it useful for patients with heart failure and myocardial ischemia. IV

nitroglycerin requires dose titration to achieve therapeutic goals. The effectiveness of prolonged infusions is limited by

the development of tachyphylaxis (loss of effect) within the first 24 hours.

Sodium Ni troprusside

Sodium nitroprusside (see Table 8) is a nitric oxide donor and a potent short-acting arterial and venous dilator.

Nitroprusside infusions generally are reserved for patients in an intensive care unit. During nitroprusside infusions,

patients should be converted to oral vasodilators such as ACE inhibitors, ARBs, or hydralazine and a nitrate.

Sodium nitroprusside should be infused for a short duration in patients with severe renal disease to prevent

accumulation of thiocyanate, the by-product of hepatic metabolism of nitroprusside, which is excreted by the kidney.

Nitroprusside should be avoided in patients with active ischemia because of its potential for coronary steal syndrome,

which shunts blood away from the ischemic myocardium to well-perfused muscle.

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib25http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib25http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib25http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig3_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig3_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig3_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib25http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045


20/28

Nesir i t ide

Nesiritide (see Table 8), synthetic BNP, is an arterial and venous vasodilator with modest diuretic and natriuretic

properties.26

Nesiritide increases cardiac output by afterload reduction without increasing heart rate or oxygen

consumption. It modulates the vasoconstrictor and sodium-retaining effects of other neurohormones. Nesiritide is

administered as a weight-based bolus followed by continuous IV infusion in patients who have acutely

decompensated heart failure and who have dyspnea at rest or with minimal activity. It may be started in the

emergency department and does not require invasive hemodynamic monitoring or frequent titration. Tolerance to the

drug does not occur and it is not arrhythmogenic. Intermittent outpatient infusions of nesiritide are not recommended

for the routine management of heart failure.

Device Therapies for Heart FailureCardiac Resynch ronization Therapy

Several clinical trials have shown the potential benefit of cardiac resynchronization therapy (CRT) for patients with

severe symptomatic heart failure and a wide QRS complex.27, 28

Symptomatic improvement is achieved in

approximately 70% of patients because of improved ventricular contraction, ventricular reverse-remodeling, and

reduction of mitral regurgitation. With cardiac resynchronization therapy (biventricular pacing), a third electrode is

implanted in a left cardiac vein via the coronary sinus so that the right and left ventricles are paced in a synchronous

fashion (Fig. 3). Optimal synchronization of atrial and ventricular contraction is achieved with echocardiographic

guidance. Guidelines for resynchronization therapy are listed in Box 2.

Box 2: Guidelines for Resynchronization Therapy

NYHA Class III or IV heart failure symptoms

Symptomatic despite medications

Left ventricular ejection fraction 35% (consider cardiac resynchronization therapy-defibrillator)

Wide QRS (>120 msec; left bundle branch block, intraventricular conduction delay)

Evidence of dyssynchrony

Defibri l lator Therapy

Approximately 50% of patients with heart failure die suddenly. Implantation of an ICD can improve survival in certain

subsets of heart failure patients and has been shown to be superior to antiarrhythmic drug therapy in preventing

sudden death.29-32

Current indications for defibrillator therapy are listed in Box 3. Cardiac resynchronization therapy

can be combined with an ICD as a single device if the patient meets criteria for both therapies, as is often the case.
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib26http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib26http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib26http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib27http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib27http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib27http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#b0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib29http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib29http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib29http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#b0025http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#b0025http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib29http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#b0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0020http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib27http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib26http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#t0045


21/28

Box 3: Indications for an Implantable Cardioverter-Defibrillator

Cardiac arrest survivor

Sustained ventricular tachycardia

Inducible ventricular tachycardia

Ischemic cardiomyopathy,*LVEF 35%

Dilated cardiomyopathy, LVEF 35% with symptoms

*40-day waiting period after myocardial infarction, stenting, bypass surgery.

9-month waiting period after diagnosis.

LVEF, left ventricular ejection fraction.

Ultrafi l trat ion Therapy

Ultrafiltration therapy is an effective method for extracting sodium and fluid from volume overloaded heart failure

patients with resistance to diuretic therapy. A reduction in rehospitalization has been observed compared with

intravenous diuretic therapy.33


Surgical OptionsLeft Ventr icu lar Assist Devices (LVADs )

Certain patients with end-stage heart failure and NYHA Class IV symptoms are referred to a tertiary care center for

mechanical circulatory support.34, 35

At present, LV assist devices (LVADs) are used either as a bridge to cardiac

transplantation in patients who are appropriate transplantation candidates or as destination therapy in patients
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#fn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#fn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#fn0010http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#fn0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#fn0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#fn0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib33http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib33http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib33http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heartfailurefig4_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib34http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib34http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib34http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heartfailurefig4_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib34http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heartfailurefig4_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib33http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#fn0015http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#fn0010


22/28

ineligible for transplantation. The inflow cannula of an LVAD is connected to the apex of the left ventricle. Blood is

mechanically pumped by the device via the outflow cannula to the aorta (Fig. 4). Complications following LVAD

implantation are common and often life threatening; these include stroke, infection, perioperative coagulopathy and

bleeding, and multisystem organ failure. Newer rotary continuous flow LVADs have proven to be more durable and

are associated with fewer complications.36

Ventr icu lar Reconstruct ion Surgery

Ventricular reconstruction surgery, also called ventricular remodeling surgery or a Dor procedure, has been

performed for heart failure secondary to ischemic cardiomyopathy.37

It consists of several components: coronary

artery bypass grafting, mitral and tricuspid valve repair, resection of LV scar or aneurysm, reshaping the left ventricle

from a spherical to an elliptic shape, and epicardial LV pacing lead placement (Fig. 5). The STICH trial failed to show

benefit over standard bypass or value surgery. Thus, the future of ventricular reconstruction surgery is uncertain.


Cardiac Transplantation

Cardiac transplantation is reserved for otherwise healthy patients who have end-stage heart failure with severely

impaired functional capacity despite optimal medical therapy (Fig. 6).38

Patients are excluded from transplantation if

they have chronic medical comorbidities, pulmonary hypertension, active infection, psychosocial contraindications, or

medical noncompliance. Survival after cardiac transplantation is about 85% at 1 year, and median life expectancy is

approximately 10 years. Complications limiting survival include rejection, infection, transplant coronary vasculopathy,

and malignancy. Following cardiac transplantation, patients are subjected to lifelong immunosuppression to prevent

rejection, which in turn renders them susceptible to various opportunistic infections and malignancies.

Back to Top

Summary
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0025http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib36http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib36http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib36http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib37http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib37http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib37http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0030http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig5_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0035http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib38http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib38http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib38http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig5_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib38http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0035http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig5_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0030http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib37http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib36http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#f0025


23/28

All heart failure patients should receive an ACE inhibitor and a beta blocker.

Diuretics are needed in most patients to manage fluid retention.

Digoxin is reserved for patients with signs and symptoms of heart failure.

Aldosterone antagonists are used in patients with Class III or IV heart failure.

ARBs or a hydralazine plus nitrate may be added to standard therapy for additional benefit.

Back to Top

Prevention and screening

Patients classified as stage A are at high risk for heart failure but without structural heart disease or heart failure

symptoms. They include patients with hypertension, diabetes mellitus, obesity, coronary artery disease, or use of

cardiotoxins and those with a family history of cardiomyopathy. Preventive therapies include treatment of lipid

disorders and hypertension, smoking cessation, regular exercise, avoidance of excess alcohol and illicit drugs, and

ACE inhibitors in appropriate patients. Patients with stage B heart failure have structural heart disease, but no

symptoms of heart failure. These include patients with previous myocardial infarction, LV systolic dysfunction, and

asymptomatic valvular disease. Therapies are prescribed to prevent LV remodeling. These include all preventive

strategies for stage A, as well as ACE inhibitors and beta blockers for appropriate patients.


Back to Top

Considerations in special populations

Heart failure is slightly more common in women than men. In women, heart failure occurs later in life, is often related

to hypertension, and is often associated with preserved LV systolic function. Women tend to have more prominent
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig6_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig6_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/images/heart-failurefig6_large.jpghttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#top


24/28

heart failure manifestations and more hospitalizations but better overall survival (except with coronary artery disease)

than men. Heart failure therapeutic agents are not gender specific.

African Americans appear to benefit from a combination of hydralazine and nitrates when added to conventional heart

failure therapy.39

Back to Top

References

1. American Heart Association. Heart Disease and Stroke Statistics2008 Update. Dallas: American Heart

Association, 2008. http://circ.ahajournals.org

2. Packer M, Coats AJ, Fowler MB, et al: Effect of carvedilol on survival in severe chronic heart failure. N Engl

J Med. 2001, 344: 1651-1658.

3. Hansen A, Haass M, Zugck C, et al: Prognostic value of Doppler echocardiographic mitral inflow patterns:

Implications for risk stratification in patients with chronic congestive heart failure. J Am Coll Cardiol. 2001,

37: 1049-1055.

4. Hunt SA, Abraham WT, Chin MH, et al: American College of Cardiology; American Heart Association Task

Force on Practice Guidelines; American College of Chest Physicians; International Society for Heart and

Lung Transplantation; Heart Rhythm Society: ACC/AHA 2005 Guideline Update for the Diagnosis and

Management of Chronic Heart Failure in the Adult: A report of the American College of Cardiology/American

Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for

the Evaluation and Management of Heart Failure): Developed in collaboration with the American College of

Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart

Rhythm Society. Circulation. 2005, 112: e154-e235.

5. Swedberg K, Cleland J, Dargie H, et al: Guidelines for the diagnosis and treatment of chronic heart failure:

Executive summary (Update 2005). Eur Heart J. 2005, 26: 1115-1140.

6. Dao Q, Krishnaswamy P, Kazanegra R, et al: Utility of B-type natriuretic peptide in the diagnosis of

congestive heart failure in an urgent-care setting. J Am Coll Cardiol. 2001, 37: 379-385.

7. Mueller C, Scholer A, Laule-Kilian K, et al: Use of B-type natriuretic peptide in the evaluation and

management of acute dyspnea. N Engl J Med. 2004, 350: 647-654.

8. SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions

and congestive heart failure (SOLVD). N Engl J Med. 1991, 325: 293-302.
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib39http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib39http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib39http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://circ.ahajournals.org/http://circ.ahajournals.org/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#bib39


25/28

9. Cohn JN, Archibald DG, Ziesche S, et al: Effect of vasodilator therapy on mortality in chronic congestive

heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1986, 314: 1547-1552.

10. Yusuf S, Sleight P, Pogue J, et al: Effects of an angiotensin-converting enzyme inhibitor, ramipril, on

cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.

N Engl J Med. 2000, 342: 145-153.

11. Packer M, Poole-Wilson PA, Armstrong PW, et al: Comparative effects of low and high doses of the

angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS

Study Group. Circulation. 1999, 100: 2312-2318.

12. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart

failure. N Engl J Med. 2001, 345: 1667-1675.

13. Yusuf S, Pfeffer MA, Swedberg K, et al: Effects of candesartan in patients with chronic heart failure and

preserved left-ventricular ejection fraction: The CHARM-Preserved Trial. Lancet. 2003, 362: 777-781.

14. Packer M, Bristow MR, Cohn JN, et al: The effect of carvedilol on morbidity and mortality in patients with

chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996, 334: 1349-1355.

15. Hjalmarson A, Goldstein S, Fagerberg B, et al: Effects of controlled-release metoprolol on total mortality,

hospitalizations, and well-being in patients with heart failure: The Metoprolol CR/XL Randomized

Intervention Trial in congestive heart failure (MERIT-HF). JAMA. 2000, 283: 1295-1302.

16. Insufficiency Cardiac. Bisoprolol Study Group: The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): A

randomised trial. Lancet. 1999, 353: 9-13.

17. Poole-Wilson PA, Swedberg K, Cleland JGF, et al: Comparison of carvedilol and metoprolol on clinical

outcomes in patients with chronic heart failure in the Carvedilol or Metoprolol European Trial (COMET):

Randomized controlled trial. Lancet. 2003, 362: 7-13.

18. Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N

Engl J Med.. 1997, 336: 525-533.

19. Brater DC. Diuretic therapy. N Engl J Med. 1998, 339: 387-395.

20. Pitt B, Zannad F, Remme WJ, et al: The effect of spironolactone on morbidity and mortality in patients with

severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999, 341: 709-

717.

21. Pitt B, Remme W, Zannad F, et al: Eplerenone, a selective aldosterone blocker, in patients with left

ventricular dysfunction after myocardial infarction. N Engl J Med. 2003, 348: 1309-1321.

22. Cohn JN, Johnson G, Ziesche S, et al: A comparison of enalapril with hydralazine-isosorbide dinitrate in the

treatment of chronic congestive heart failure. N Engl J Med. 1991, 325: 303-310.


26/28

23. Packer M, OConnor CM, Ghali JK, et al: Effect of amlodipine on morbidity and mortality in severe chronic

heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group. N Engl J Med. 1996,

335: 1107-1114.

24. Felker GM, OConnor CM. Inotropic therapy for heart failure: An evidence-based approach. Am Heart J.

2001, 142: 393-401.

25. Cuffe MS, Califf RM, Adams KF, et al: Short-term intravenous milrinone for acute exacerbation of chronic

heart failure. A randomized controlled trial. JAMA. 2002, 287: 1541-1547.

26. Iyengar S, Feldman DS, Trupp R, Abraham WT. Nesiritide for the treatment of congestive heart failure.

Expert Opin Pharmacother. 2004, 5: 901-907.

27. Abraham WT, Fisher WG, Smith AL, et al: Cardiac resynchronization in chronic heart failure. N Engl J Med.

2002, 346: 1845-1853.

28. Cleland JGF, Daubert JC, Erdman E, et al: The effect of cardiac resynchronization on morbidity and

mortality in heart failure. N Engl J Med. 2005, 352: 1539-1549.

29. Gollob MH, Seger JJ. Current status of the implantable cardioverter-defibrillator. Chest. 2002, 119: 1210-

1221.

30. Moss AJ, Zareba W, Hall WJ, et al: Prophylactic implantation of a defibrillator in patients with myocardial

infarction and reduced ejection fraction. N Engl J Med. 2002, 346: 877-883.

31. Kadish A, Dyer A, Daubert JP, et al: Prophylactic defibrillator implantation in patients with nonischemic

dilated cardiomyopathy. N Engl J Med. 2004, 350: 2151-2158.

32. Bardy GH, Lee KL, Mark DB, et al: Amiodarone or an implantable cardioverter-defibrillator for congestive

heart failure. N Engl J Med. 2005, 352: 225-237.

33. Costanzo MR, Guglin ME, Saltzberg MT, et al: Ultrafiltration versus intravenous diuretics for patients

hospitalized for acute decompensated heart failure. J Am Coll Cardiol. 2007, 49: 675-683.

34. Rose EA, Gelijns AC, Moskowitz AJ, et al: Long-term use of a left ventricular assist device for end-stage


35. Delgado DH, Rao V, Ross HJ, et al: Mechanical circulatory assistance: State of the art. Circulation. 2002,

106: 2046-2050.

36. John R, Kamdar F, Liao K, et al: Disproved survival and decreasing incidence of adverse events with the

heart mate II left ventricular assist device as bridge-to-transplant therapy. Ann Thorac Surg. 2008, 86: 1227-

1235.

37. Mickleborough LL, Merchant N, Ivanov J, et al: Left ventricular reconstruction: Early and late results. J

Thorac Cardiovasc Surg. 2004, 128: 27-37.

38. Hunt SA.. Current status of cardiac transplantation. JAMA. 1998, 280: 1692-1698.


27/28

39. Cohn JN, Tam W, Anard IS, et al: Isosorbide dinitrate and hydralazine in a fixed-dose combination produces

further regression of left ventricular remodeling in a well-treated block population with heart failure: Results

from A-HeFT. J Cardiac Fail. 2007, 13: 331-339.

Back to Top

Suggest Readings

Adams KF, Lindenfeld J, Arnold JMO, et al: Executive summary: HFSA 2006 comprehensive heart failure

practice guideline. J Cardiac Failure. 2006, 12: 10-38.

American Heart Association. Heart Disease and Stroke Statistics-2008 Update. Dallas: American Heart

Association, 2008.

Bardy GH, Lee KL, Mark DB, et al: Amiodarone or an implantable cardioverter-defibrillator for congestive


Brater DC. Diuretic therapy. N Engl J Med. 1998, 339: 387-395.

Cleland JGF, Daubert JC, Erdman E, et al: The effect of cardiac resynchronization on morbidity and

mortality in heart failure. N Engl J Med. 2005, 352: 1539-1549.

Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N

Engl J Med. 1997, 336: 525-533.

Hjalmarson A, Goldstein S, Fagerberg B, et al: Effects of controlled-release metoprolol on total mortality,

hospitalizations, and well-being in patients with heart failure: The Metoprolol CR/XL Randomized

Intervention Trial in congestive heart failure (MERIT-HF). JAMA. 2000, 283: 1295-1302.

Hunt SA, Abraham WT, Chin MH, et al: American College of Cardiology; American Heart Association Task

Force on Practice Guidelines; American College of Chest Physicians; International Society for Heart and

Lung Transplantation; Heart Rhythm Society: ACC/AHA 2005 Guideline Update for the Diagnosis and

Management of Chronic Heart Failure in the Adult: A report of the American College of Cardiology/American

Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for

the Evaluation and Management of Heart Failure): Developed in collaboration with the American College of

Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart

Rhythm Society. Circulation. 2005, 112: e154-e235.

Mueller C, Scholer A, Laule-Kilian K, et al: Use of B-type natriuretic peptide in the evaluation and

management of acute dyspnea. N Engl J Med. 2004, 350: 647-654.

Pitt B, Remme W, Zannad F, et al: Eplerenone, a selective aldosterone blocker, in patients with left

ventricular dysfunction after myocardial infarction. N Engl J Med. 2003, 348: 1309-1321.
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#tophttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/#top


28/28

Pitt B, Zannad F, Remme WJ, et al: The effect of spironolactone on morbidity and mortality in patients with

severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999, 341: 709-

717.

Swedberg K, Cleland J, Dargie H, et al: Guidelines for the diagnosis and treatment of chronic heart failure:

Executive summary (Update 2005). Eur Heart J. 2005, 26: 1115-1140.

Copyright 2000-2013 The Cleveland Clinic Foundation. All Rights Reserved.Center for Continuing Education | 9500 Euclid Avenue, KK31, Cleveland, OH 44195

Main Cleveland Clinic Website

Accreditation with Commendation

Awards

Site Disclaimer

Privacy Policy

Feedback

Sitemap
http://my.clevelandclinic.org/http://www.clevelandclinicmeded.com/accreditation.htmlhttp://www.clevelandclinicmeded.com/awards.htmhttp://www.clevelandclinicmeded.com/site-disclaimer.htmlhttp://www.clevelandclinicmeded.com/privacy-policy.htmlhttp://www.clevelandclinicmeded.com/info.htmhttp://www.clevelandclinicmeded.com/sitemap.htmhttp://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/heart-failure/http://www.clevelandclinicmeded.com/sitemap.htmhttp://www.clevelandclinicmeded.com/info.htmhttp://www.clevelandclinicmeded.com/privacy-policy.htmlhttp://www.clevelandclinicmeded.com/site-disclaimer.htmlhttp://www.clevelandclinicmeded.com/awards.htmhttp://www.clevelandclinicmeded.com/accreditation.htmlhttp://my.clevelandclinic.org/

Documents

Impaired Relaxation of the Heart