- Email: [email protected]
Approach to Patients With Heart Failure and Normal Ejection Fraction
Mayo Clin Proc, October 2001, Vol 76
Heart Failure and Normal Ejection Fraction
1047
Concise Review for Clinicians
Approach to Patients With Heart Failure and Normal Ejection Fraction AHMAD A. ELESBER, MD, AND MARGARET M. REDFIELD, MD Approximately 50% of patients with a firm clinical diagnosis of heart failure (HF) have a normal ejection fraction. Some patients have valvular disease, but most have underlying diastolic dysfunction that leads to pulmonary and systemic congestion and signs and symptoms of HF. Although diastolic HF is clinically and radiographically indistinguishable from HF with depressed left systolic ventricular function, knowledge of which patients are at risk of diastolic HF, the common clinical profiles, and the com-
mon echocardiographic findings enhances the clinician’s ability to diagnose diastolic HF with confidence. The prognostic implications of a diagnosis of diastolic HF and the therapeutic approach to such patients are reviewed. Mayo Clin Proc. 2001;76:1047-1052 ACE = angiotensin-converting enzyme; EF = ejection fraction; HF = heart failure
D
iastolic dysfunction is an abnormality in left ventricular myocardial relaxation and/or compliance that alters the ease with which blood is accepted into the left ventricle during diastole and thus the pressures that must be present in the left atrium to ensure adequate filling. Of importance, all patients with systolic dysfunction have concomitant diastolic dysfunction; thus, there is no such entity as pure systolic heart failure (HF).1 Indeed, the level of diastolic dysfunction in patients with reduced systolic function influences the severity of their symptoms.2 In contrast, cardiovascular disease may lead to diastolic dysfunction in the absence of concomitant systolic dysfunction.3 Although diastolic dysfunction was previously known to occur in rare diseases such as hypertrophic cardiomyopathy, it is now clear that hypertension and coronary artery disease commonly produce diastolic dysfunction in the absence of significant reductions in ejection fraction (EF).
Framingham criteria (Table 1), enhance the specificity of the diagnosis but are relatively insensitive for the diagnosis of milder degrees of HF. The Framingham criteria identify a patient subset with an extremely poor prognosis.4 When the Framingham criteria were developed, noninvasive cardiac imaging was not available, and thus the criteria did not include assessment of systolic function. Indeed, numerous studies have shown that 40% to 60% of subjects satisfying these criteria have a normal EF. A recent review of 31 studies of patients with a clinical diagnosis of HF showed that on average 40% of patients with HF had a normal EF.5 These studies were limited by their small numbers and the hospital-based settings, factors that limit generalization of the results. A community-based study in Olmsted County, Minnesota, found that 43% of incident cases of HF had preserved EF (≥50%).6 Data from the Framingham study suggest that 51% of patients with HF have preserved systolic function.3 A population-based study that targeted patients older than 65 years and included African Americans found that 55% of patients with HF had an EF of 55% or higher.7 Patients with well-documented signs, symptoms, and radiographic evidence of HF with normal systolic function (commonly assessed by EF) are believed to have a primary impairment of diastolic function that results in the need for elevated atrial pressure to maintain filling. This syndrome has been termed diastolic heart failure. Patients with HF and a normal EF have a worse prognosis than age-matched controls without HF symptoms.3,6 However, whether the prognosis for patients with diastolic HF is better than that of patients with HF and reduced systolic function (systolic HF) is unclear. Reported annual mortality rates for patients with diastolic HF vary from 1.3% to 17.5% compared with 15% to 20% for patients with systolic HF.5 A community-based study of incident
HF WITH NORMAL SYSTOLIC FUNCTION—IS IT HF? Heart failure is a clinical syndrome characterized by an abnormality of cardiac function that results in exercise intolerance and exertional or resting dyspnea accompanied by signs and radiographic evidence of pulmonary and systemic venous congestion. The diagnosis of HF is clinical. Standardized criteria for the diagnosis of HF, such as the From the Department of Internal Medicine (A.A.E.) and Division of Cardiovascular Diseases and Internal Medicine (M.M.R.), Mayo Clinic, Rochester, Minn. A question-and-answer section appears at the end of this article. Address reprint requests and correspondence to Margaret M. Redfield, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: redfield.margaret @mayo.edu). Mayo Clin Proc. 2001;76:1047-1052
1047
© 2001 Mayo Foundation for Medical Education and Research
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
1048
Heart Failure and Normal Ejection Fraction
Table 1. Framingham Criteria for Heart Failure* Major Paroxysmal nocturnal dyspnea Neck-vein distention Rales Cardiomegaly on radiography (or increasing heart size on chest x-ray film) Acute pulmonary edema S3 gallop Increased central venous pressure (>16 cm H2O at right atrium) Circulation time ≥25 seconds Hepatojugular reflux Pulmonary edema, visceral congestion, or cardiomegaly at autopsy Minor Bilateral ankle edema Nocturnal cough Dyspnea on ordinary exertion Hepatomegaly Pleural effusion Decrease in vital capacity by one third from maximal value recorded Tachycardia (heart rate ≥120 beats/min) Major or minor Weight loss ≥4.5 kg in 5 days in response to treatment of heart failure *The diagnosis of heart failure requires that 2 major or 1 major and 2 minor criteria be present concurrently. Minor criteria were acceptable only if they could not be attributed to another medical condition. Patients who fulfill these criteria have an adverse prognosis regardless of the measured ejection fraction.
cases of HF found that survival at 3 months, 1 year, and 5 years was 86%, 76%, and 35%, respectively, and that survival was not significantly different for patients with diastolic HF vs systolic HF.6 This finding was later confirmed in 7 other small studies that analyzed survival in elderly patients with well-confirmed HF. Thus, when the diagnosis of HF in elderly patients is confirmed by Framingham criteria, prognosis may be similar in those with diastolic HF and systolic HF. Diseases that lead to systolic HF and diastolic HF are similar. Hypertension and coronary artery disease may manifest as isolated diastolic dysfunction or as combined systolic and diastolic dysfunction.3,6,8 Hypertrophic or restrictive cardiomyopathies and constrictive pericarditis are rare causes of diastolic HF, which may be more common in younger patients. Valvular disease can cause symptoms of HF in patients with a normal EF, and patients with severe valvular disease (moderate to severe or severe regurgitant or stenotic lesions of the mitral, tricuspid, and aortic valves) are not considered to have diastolic HF.9 Long-standing valvular disease can produce irreversible changes in left ventricular structure and myocardial function, which can manifest as diastolic dysfunction. Therefore, a patient who has new or
Mayo Clin Proc, October 2001, Vol 76
persistent symptoms and a normal EF after valve surgery with a normally functioning repair/replacement would be considered to have diastolic HF. A controversial theory is that the aging process is associated with altered diastolic function and that diastolic HF may develop in elderly patients in the absence of cardiovascular disease. HOW TO DIAGNOSE DIASTOLIC HF Diagnose HF An accurate diagnosis of the clinical syndrome of HF is the most crucial step in diagnosing diastolic HF. Dyspnea, exercise intolerance, and edema are common signs and symptoms but individually are not synonymous with HF because each can be caused by other conditions (deconditioning, pulmonary disease, obesity, venous disease, etc). Thus, the clinician must first determine whether the syndrome of HF is present. If the patient fulfills the Framingham criteria (Table 1), the diagnosis of HF is clear. In patients with suggestive but less severe symptoms, additional clinical information may enhance the suspicion of HF. The presence of cardiovascular disease (hypertension, coronary or previous [corrected] valvular disease) or risk factors for coronary artery disease strengthen the suspicion. The absence of lung disease on history, physical examination, chest radiography, or pulmonary function tests and the absence of tobacco use make a pulmonary etiology unlikely. Although some experts are reluctant to diagnose diastolic HF in the presence of lung disease, lung disease related to smoking is extremely common, and such patients frequently have concomitant obstructive lung disease and systolic HF. Thus, a diagnosis of lung disease should not exclude diastolic HF if clear-cut signs and symptoms of HF are present. The response to diuretics is often helpful in confirming concomitant HF in such patients. If a patient was previously active and has experienced a sudden or subacute reduction in exercise tolerance, deconditioning is not a likely explanation for the patient’s symptoms. Anemia, thyroid dysfunction, or other systemic disease can be excluded by findings on clinical examination and basic testing. However, anemia and infection commonly precipitate episodes of HF in patients with underlying ventricular dysfunction. Thus, the presence of these conditions does not exclude concomitant HF. An important feature of symptoms related to HF is that the symptoms improve with diuretics. Thus, a patient’s response to diuretics is part of the Framingham criteria, and improvement of symptoms (other than edema alone) after a trial of diuretics is highly suggestive of HF. Determine Whether Systolic Dysfunction is Present Early hospital-based studies confirmed that clinical features and physical examination findings fail to distinguish
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Mayo Clin Proc, October 2001, Vol 76
systolic HF from diastolic HF.5 Community-based studies also revealed that no clinical characteristics reliably identified patients with normal systolic function. Although advanced age, history of hypertension, female sex, and absence of myocardial infarction were associated with preserved EF, these features were often present in patients with systolic HF, and neither these features nor New York Heart Association class or chest x-ray films were helpful to distinguish systolic HF from diastolic HF. Guidelines from the American College of Cardiology/American Heart Association recommend echocardiography in all patients with suspected HF.10 Echocardiography should be performed while the patient is symptomatic (before treatment) if possible. If EF is reduced substantially (<40%), the patient should receive standard therapy for systolic HF, as established by clinical trials and summarized in numerous reviews and position papers, with angiotensin-converting enzyme (ACE) inhibitors, β-blockers, digoxin, and diuretics as needed to control symptoms.10,11 Patients with “borderline” systolic function (EF, 40%-50%) should be considered individually. The clinician may want to consider assessing EF with an alternative modality. If EF is only mildly impaired, the clinician should consider the diagnosis of diastolic HF. Can Diastolic HF Be Diagnosed Confidently If EF is Normal? Although the “working definition” of diastolic HF in most studies published to date has been clinical HF with normal EF, details of the definition of diastolic HF have varied substantially. Disagreement exists over what should be considered a “normal” EF, how soon the EF must be assessed after HF has been diagnosed, and whether measurement of hemodynamics or other tests for the presence of diastolic dysfunction must be performed. Recently, 2 different standardized diagnostic criteria for diastolic HF were suggested. The European criteria suggest that a patient not only have HF with a normal EF (defined as >45%) but also some objective quantification (Doppler echocardiography or invasive hemodynamics) of diastolic dysfunction.12 The criteria suggested by Vasan and Levy9 require a more stringent definition of a normal EF (>50%) and necessitate invasive hemodynamic data to confirm definite diastolic HF. Classification as probable or possible diastolic HF is based on proximity of the EF determination to the patient’s symptoms (<3 days for probable and >3 days for possible) and on supportive clinical features. Although these criteria are helpful, they are as yet untested in their ability to identify patients with an adverse prognosis who might respond to a standardized treatment approach. Commonsense guidelines for diagnosing diastolic HF are summarized in Table 2. Patients who have suggestive symptoms but do not fulfill Framingham criteria for HF
Heart Failure and Normal Ejection Fraction
1049
Table 2. Clinical Features Suggestive of Diastolic Heart Failure* Fulfillment of Framingham criteria for HF Ejection fraction >50% while the patient is symptomatic or soon (3 days) after initial treatment Consistent clinical scenario Elderly patient (especially female) History of hypertension Hypertension at presentation Recent onset of tachyarrhythmia coincident with HF episode Coronary disease without previous myocardial infarction or Q waves HF not explained by presence of uncorrected valvular disease *HF = heart failure.
must be considered individually, and patients who fit the typical profile may be more likely to have HF and should be offered a trial of HF treatment if they have no noncardiac reason for their symptoms. Although prompt assessment of systolic function is recommended, a recent study suggested that EF measured during an episode of hypertensive pulmonary edema is similar to that measured within 1 to 3 days after the acute episode.13 Certain clinical features are common among patients with diastolic HF. Approximately 30% of patients with diastolic HF present with recent-onset atrial fibrillation or flutter.6,14 Patients with underlying diastolic dysfunction rely on “atrial kick” to maintain filling with normal mean atrial pressures. Loss of atrial kick and tachycardia often present with newonset atrial fibrillation result in the need for higher atrial pressures to maintain filling in the presence of underlying diastolic dysfunction and may precipitate HF. Likewise, worsening diastolic function and chronic elevation in left atrial pressures may precipitate onset of atrial fibrillation. Many patients with diastolic HF have hypertension at presentation. Although poorly controlled hypertension can precipitate an HF episode in patients with systolic dysfunction, it is particularly common among patients with diastolic HF. Finally, ischemia may worsen diastolic function without decreasing EF. Thus, patients presenting with ischemia may have diastolic HF. Does Diastolic Function Need To Be Measured? Noninvasive assessment of diastolic function has advanced considerably in recent years, and Doppler echocardiography can evaluate diastolic function and detect the presence of increased filling pressures in most patients.2,15,16 However, skilled and informed assessment of diastolic function is not yet standard in all echocardiographic laboratories. Indeed, many erroneous statements may be made concerning diastolic function when assessment is incomplete. If an echocardiography laboratory can provide a comprehensive assessment of diastolic function that does
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
1050
Heart Failure and Normal Ejection Fraction
Table 3. Treatment of Diastolic Heart Failure* Improve acute symptoms Diuretics Treat precipitating factors and underlying disease Hypertension: diuretics, β-blockers, ACE inhibitors, ARB, calcium channel blockers Ischemia: β-blockers, calcium channel blockers, nitrates, revascularization Atrial arrhythmia Control heart rate: β-blockers, calcium channel blockers, digoxin Maintain sinus rhythm: cardioversion, antiarrhythmics Prevent emboli: warfarin Improve survival ? β-Blockers ? ACE inhibitors Prevent relapse into symptomatic HF by intensifying outpatient follow-up Control blood pressure Provide dietary counseling (sodium) Monitor volume status (daily weights, diuretic adjustment) Maintain normal sinus rhythm Institute exercise program *ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blockers; HF = heart failure.
not rely solely on the mitral inflow pattern, confirmation of abnormal diastolic function can strengthen the diagnosis of diastolic HF. However, diastolic function may not be assessed or may be interpreted improperly. Laboratory personnel who rely only on the mitral inflow signal to characterize diastolic function may report that diastolic function is normal, but numerous studies have shown that the mitral inflow pattern may be “pseudonormal” in the presence of substantially elevated atrial pressures.15 Doppler echocardiographic assessment of diastolic function was reviewed recently.2 If the patient has clear-cut HF and a normal EF, these criteria should influence diagnosis and treatment. Some simple echocardiographic criteria may be helpful in the absence of a comprehensive diastolic assessment. Left atrial enlargement often reflects long-standing elevation of atrial pressures, and its presence supports the diagnosis of diastolic HF. Left ventricular hypertrophy, although not invariably present, also supports the diagnosis because of its association with diastolic dysfunction. Elevated right-sided diastolic pressures in the absence of pulmonary vascular disease can be detected by measuring the tricuspid regurgitant velocity, and such pressures support the diagnosis of elevated left-sided diastolic pressures. A wall motion abnormality in the absence of a reduction in global systolic function also supports the diagnosis of diastolic HF. TREATING DIASTOLIC HF The best current strategy for patients with diastolic HF is to treat the underlying etiologies (hypertension, coronary ar-
Mayo Clin Proc, October 2001, Vol 76
tery disease) and the precipitating factors (labile hypertension, ischemia, tachyarrhythmias). Therapy for diastolic HF (Table 3) should target 4 goals: provide symptomatic relief, treat underlying disease and precipitating factors, improve survival, and reduce other adverse outcomes (rehospitalization). Diuretics When a patient has evidence of venous congestion, the most direct treatment is diuretics. Caution must be used because some patients with diastolic HF are sensitive to the preload reduction and may develop hypotension or severe prerenal azotemia. Diuretics have also been proved to control blood pressure and to reverse left ventricular hypertrophy. Although the need for maintenance therapy with diuretics must be assessed in each patient, the patient with acute symptoms requires diuretics, and most patients with severe diastolic HF require some maintenance therapy. Intravenous agents should be used for acute symptoms. Long-term oral dosing should be adjusted to maintain a patient’s weight at the time the symptoms were controlled, based on daily weights. Nitrates Nitrates may be useful because of their preload-reducing and anti-ischemic effects.10 Indeed, the Vasodilator Heart Failure Trial showed a trend toward better survival among patients with HF and an EF greater than 45% who received isosorbide dinitrate plus hydralazine.17 Dosing as for coronary artery disease is appropriate. Calcium Channel Blockers Calcium channel blockers are well known for their antihypertensive, anti-ischemic, and negative chronotropic effects and can be helpful. A small placebo-controlled, double-blinded, 5-week crossover trial showed that verapamil improved exercise capacity and HF score.18 This improvement occurred with a decrease in heart rate but with no change in blood pressure compared with baseline or placebo. Although calcium channel blockers do not immediately improve diastolic function when initially administered,19 these drugs are useful to treat conditions that precipitate diastolic HF (hypertension and ischemia). Dosing should be targeted at controlling blood pressure and angina. Angiotensin II Receptor Blockers and ACE Inhibitors Angiotensin II receptor blockers and ACE inhibitors can be used for their antihypertensive effect. In patients known to have diastolic dysfunction and a hypertensive response to exercise, losartan improved exercise time, quality of life, and exercise systolic blood pressure.20 A
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Mayo Clin Proc, October 2001, Vol 76
meta-analysis suggested that ACE inhibitors have the strongest effect on regression of left ventricular hypertrophy, and thus they may improve diastolic function via their antihypertrophic effect. In patients with diastolic HF and prior myocardial infarction, enalapril improved New York Heart Association function class and treadmill exercise duration compared to placebo.21 Two retrospective studies showed that survival was associated with ACE inhibitor therapy in patients with diastolic HF.22,23 In these retrospective studies, ACE inhibitors were likely used to treat hypertension rather than HF per se. Prospective trials are needed to evaluate the effectiveness of angiotensin II receptor blockers and ACE inhibitors in diastolic HF. Until then, dosing should be targeted at controlling blood pressure. β-Blockers β-Blockers can be used to control hypertension, ischemia, and tachycardia and thus may be useful in patients with diastolic HF associated with these factors. A retrospective study showed that β-blockers were independently associated with improved survival in patients with diastolic HF.22 β-Blockers do not improve diastolic function immediately but may result in long-term improvement analogous to their effect on systolic function in patients with systolic HF.24 Currently, β-blockers should be used to treat underlying disease as their benefit for diastolic HF per se is unproved. Thus, dosing would be as needed for control of blood pressure and ischemic symptoms.
Heart Failure and Normal Ejection Fraction
REFERENCES 1. 2. 3.
4. 5. 6. 7.
8. 9. 10.
11.
12. 13.
Digoxin Digoxin is not recommended specifically for diastolic HF and can be deleterious in certain situations (hypertrophic cardiomyopathy). In patients with diastolic HF and atrial arrhythmia, digoxin may be needed to control heart rate. Recommendations Recommendations for the therapeutic approach to the patient with diastolic HF are summarized in Table 3. Unfortunately, most clinical trials to date have focused exclusively on patients with HF and systolic dysfunction. Only recently have trials been undertaken to address the potential benefit of medical treatment of diastolic HF. Until the results of such trials are available, aggressive treatment of the underlying disease and precipitating factors and close outpatient follow-up after the diagnosis is made remain the only treatment approach available for the patient with diastolic HF. Finally, aggressive treatment of blood pressure has been documented to prevent HF,25 and because hypertension is the most common factor leading to diastolic HF, the importance of prevention of diastolic HF through aggressive management of hypertension cannot be overemphasized.
1051
14.
15. 16.
17. 18.
19. 20.
21.
Brutsaert DL, Sys SU. Diastolic dysfunction in heart failure. J Card Fail. 1997;3:225-242. Lainchbury JG, Redfield MM. Doppler echocardiographic-guided diagnosis and therapy of heart failure. Curr Cardiol Rep. 1999; 1:55-66. Vasan RS, Larson MG, Benjamin EJ, Evans JC, Reiss CK, Levy D. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort. J Am Coll Cardiol. 1999;33:1948-1955. Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation. 1993;88:107-115. Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol. 1995;26:1565-1574. Senni M, Tribouilloy CM, Rodeheffer RJ, et al. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation. 1998;98:2282-2289. Kitzman DW, Gardin JM, Arnold A, et al, CHS Reseach Group. Heart failure with preserved systolic LV function in the elderly: clinical and echocardiographic correlates from the Cardiovascular Health Study [abstract]. Circulation. 1996;94(suppl 1):I-433. Abstract 2528. Vasan RS, Levy D. The role of hypertension in the pathogenesis of heart failure: a clinical mechanistic overview. Arch Intern Med. 1996;156:1789-1796. Vasan RS, Levy D. Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation. 2000;101:2118-2121. Guidelines for the evaluation and management of heart failure: report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). Circulation. 1995;92:2764-2784. Consensus recommendations for the management of chronic heart failure: on behalf of the membership of the Advisory Council To Improve Outcomes Nationwide in Heart Failure. Am J Cardiol. 1999;83(2A):1A-38A. European Study Group on Diastolic Heart Failure. How to diagnose diastolic heart failure. Eur Heart J. 1998;19:990-1003. Gandhi SK, Powers JC, Nomeir A-M, et al. The pathogenesis of acute pulmonary edema associated with hypertension. N Engl J Med. 2001;344:17-22. Chen HH, Lainchbury JG, Senni M, Redfield MM. Diastolic heart failure in the community: underlying cardiovascular diseases and precipitating factors [abstract]. Circulation. 2000;102(suppl 2):II780. Abstract 3769. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician’s Rosetta Stone. J Am Coll Cardiol. 1997;30:8-18. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation. 2000;102:17881794. Cohn JN, Johnson G, Veterans Administration Cooperative Study Group. Heart failure with normal ejection fraction: the V-HeFT Study. Circulation. 1990;81(2, suppl):III48-III53. Setaro JF, Zaret BL, Schulman DS, Black HR, Soufer R. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Am J Cardiol. 1990;66:981-986. Nishimura RA, Schwartz RS, Holmes DR Jr, Tajik AJ. Failure of calcium channel blockers to improve ventricular relaxation in humans. J Am Coll Cardiol. 1993;21:182-188. Warner JG Jr, Metzger DC, Kitzman DW, Wesley DJ, Little WC. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. J Am Coll Cardiol. 1999;33:1567-1572. Aronow WS, Kronzon I. Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fraction. Am J Cardiol. 1993;71:602-604.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
1052
22.
23.
24. 25.
Heart Failure and Normal Ejection Fraction
Chen HH, Lainchbury JG, Redfield MM. Factors influencing survival in patients with diastolic heart failure in Olmsted County, MN in 1996-97 [abstract]. Circulation. 2000;102(suppl 2):II-412. Abstract 2006. Philbin EF, Rocco TA Jr, Lindenmuth NW, Jenkins PL. Angiotensin-converting enzyme inhibitor use in diastolic heart failure is associated with a reduced risk of death [abstract]. J Am Coll Cardiol. 2000;35(suppl A):232A. Abstract 1010-172. Eichhorn EJ, Bristow MR. Medical therapy can improve the biological properties of the chronically failing heart: a new era in the treatment of heart failure. Circulation. 1996;94:2285-2296. Kostis JB, Davis BR, Cutler J, et al, SHEP Cooperative Research Group. Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA. 1997;278:212-216.
Questions About Patients With HF and Normal EF
Mayo Clin Proc, October 2001, Vol 76
b.
c.
1. Which one of the following is true? a. Patients with HF and reduced EF are usually more symptomatic than patients with diastolic HF b. Patients presenting with severe hypertension and HF symptoms are unlikely to have a normal EF c. Patients with diastolic HF are less likely to have jugular vein distention and a third heart sound compared with those who have HF and reduced EF d. Patients with underlying diastolic dysfunction are likely to develop HF with onset of atrial fibrillation e. Patients with new-onset diastolic HF could not have experienced myocardial infarction in the past 2. Which one of the following most commonly causes diastolic HF? a. Hypertrophic cardiomyopathy b. Constrictive pericarditis c. Hypertension alone or concomitant with coronary artery disease d. Amyloid heart disease e. Valvular heart disease 3. Which one of the following is true when echocardiography in a patient with HF reveals a normal EF (>50%)? a. EF was probably lower at initial patient presentation b. Presence of left atrial enlargement supports diagnosis of diastolic HF c. Presence of wall motion abnormalities precludes diagnosis of diastolic HF d. Absence of left ventricular hypertrophy precludes diagnosis of diastolic HF e. “Normal” mitral inflow pattern precludes diagnosis of diastolic HF 4. Which one of the following patients is most likely to have diastolic HF? a. A 65-year-old sedentary woman with no history of hypertension, coronary artery disease, diabetes mellitus, or smoking but with known venous insufficiency presents with edema, exertional
d.
e.
dyspnea, and fatigue without paroxysmal nocturnal dyspnea, orthopnea, or exertional dyspnea. Chest radiography shows normal heart size and no evidence of pulmonary venous hypertension. An 85-year-old woman with a long history of poorly controlled systolic hypertension presents with a 1week history of tachypalpitations, progressive dyspnea, paroxysmal nocturnal dyspnea, orthopnea, and edema. Her blood pressure is 198/85 mm Hg on admission. Chest radiography shows cardiomegaly and pulmonary venous hypertension. Electrocardiography reveals atrial fibrillation with rapid ventricular response, voltage criteria for left ventricular hypertrophy, and no Q waves. A 53-year-old man with previous myocardial infarction but no known HF presents with a 3-week history of exertional dyspnea, orthopnea, fatigue, and edema. Chest radiography shows cardiomegaly and pulmonary venous hypertension. Electrocardiography reveals Q waves in leads V1 through V5. A 72-year-old man with severe obstructive lung disease presents with worsening dyspnea. He has no history of hypertension or coronary artery disease. Chest radiography shows normal heart size, hyperinflation with flattened diaphragms, and emphysematous changes most prominent in the upper lung fields. Electrocardiography reveals low anterior forces. A trial of diuretics results in no improvement in dyspnea. A 70-year-old woman known to have metastatic colon cancer was admitted to the hospital for right hip arthroplasty. One week after discharge the patient noted new-onset dyspnea on exertion. She has no history of hypertension or coronary artery disease. Chest radiography shows normal heart size, and electrocardiography reveals sinus tachycardia.
5. Which one of the following is false concerning treatment of diastolic HF? a. No prospective randomized clinical trial has yet shown that β-blockers and ACE inhibitors improve survival in patients with diastolic HF b. β-Blockers should not be used for diastolic HF because they have not been shown to improve acute symptoms of diastolic dysfunction c. Diuretics and nitrates are useful to control fluid overload states in patients with diastolic HF d. Digoxin can be used in patients with diastolic HF and atrial fibrillation e. Restoration and maintenance of sinus rhythm may improve symptoms in patients who present with new-onset atrial fibrillation, HF, and a normal EF
Correct answers: 1. d, 2. c, 3. b, 4. b, 5. b
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Heart Failure and Normal Ejection Fraction
1047
Concise Review for Clinicians
Approach to Patients With Heart Failure and Normal Ejection Fraction AHMAD A. ELESBER, MD, AND MARGARET M. REDFIELD, MD Approximately 50% of patients with a firm clinical diagnosis of heart failure (HF) have a normal ejection fraction. Some patients have valvular disease, but most have underlying diastolic dysfunction that leads to pulmonary and systemic congestion and signs and symptoms of HF. Although diastolic HF is clinically and radiographically indistinguishable from HF with depressed left systolic ventricular function, knowledge of which patients are at risk of diastolic HF, the common clinical profiles, and the com-
mon echocardiographic findings enhances the clinician’s ability to diagnose diastolic HF with confidence. The prognostic implications of a diagnosis of diastolic HF and the therapeutic approach to such patients are reviewed. Mayo Clin Proc. 2001;76:1047-1052 ACE = angiotensin-converting enzyme; EF = ejection fraction; HF = heart failure
D
iastolic dysfunction is an abnormality in left ventricular myocardial relaxation and/or compliance that alters the ease with which blood is accepted into the left ventricle during diastole and thus the pressures that must be present in the left atrium to ensure adequate filling. Of importance, all patients with systolic dysfunction have concomitant diastolic dysfunction; thus, there is no such entity as pure systolic heart failure (HF).1 Indeed, the level of diastolic dysfunction in patients with reduced systolic function influences the severity of their symptoms.2 In contrast, cardiovascular disease may lead to diastolic dysfunction in the absence of concomitant systolic dysfunction.3 Although diastolic dysfunction was previously known to occur in rare diseases such as hypertrophic cardiomyopathy, it is now clear that hypertension and coronary artery disease commonly produce diastolic dysfunction in the absence of significant reductions in ejection fraction (EF).
Framingham criteria (Table 1), enhance the specificity of the diagnosis but are relatively insensitive for the diagnosis of milder degrees of HF. The Framingham criteria identify a patient subset with an extremely poor prognosis.4 When the Framingham criteria were developed, noninvasive cardiac imaging was not available, and thus the criteria did not include assessment of systolic function. Indeed, numerous studies have shown that 40% to 60% of subjects satisfying these criteria have a normal EF. A recent review of 31 studies of patients with a clinical diagnosis of HF showed that on average 40% of patients with HF had a normal EF.5 These studies were limited by their small numbers and the hospital-based settings, factors that limit generalization of the results. A community-based study in Olmsted County, Minnesota, found that 43% of incident cases of HF had preserved EF (≥50%).6 Data from the Framingham study suggest that 51% of patients with HF have preserved systolic function.3 A population-based study that targeted patients older than 65 years and included African Americans found that 55% of patients with HF had an EF of 55% or higher.7 Patients with well-documented signs, symptoms, and radiographic evidence of HF with normal systolic function (commonly assessed by EF) are believed to have a primary impairment of diastolic function that results in the need for elevated atrial pressure to maintain filling. This syndrome has been termed diastolic heart failure. Patients with HF and a normal EF have a worse prognosis than age-matched controls without HF symptoms.3,6 However, whether the prognosis for patients with diastolic HF is better than that of patients with HF and reduced systolic function (systolic HF) is unclear. Reported annual mortality rates for patients with diastolic HF vary from 1.3% to 17.5% compared with 15% to 20% for patients with systolic HF.5 A community-based study of incident
HF WITH NORMAL SYSTOLIC FUNCTION—IS IT HF? Heart failure is a clinical syndrome characterized by an abnormality of cardiac function that results in exercise intolerance and exertional or resting dyspnea accompanied by signs and radiographic evidence of pulmonary and systemic venous congestion. The diagnosis of HF is clinical. Standardized criteria for the diagnosis of HF, such as the From the Department of Internal Medicine (A.A.E.) and Division of Cardiovascular Diseases and Internal Medicine (M.M.R.), Mayo Clinic, Rochester, Minn. A question-and-answer section appears at the end of this article. Address reprint requests and correspondence to Margaret M. Redfield, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: redfield.margaret @mayo.edu). Mayo Clin Proc. 2001;76:1047-1052
1047
© 2001 Mayo Foundation for Medical Education and Research
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
1048
Heart Failure and Normal Ejection Fraction
Table 1. Framingham Criteria for Heart Failure* Major Paroxysmal nocturnal dyspnea Neck-vein distention Rales Cardiomegaly on radiography (or increasing heart size on chest x-ray film) Acute pulmonary edema S3 gallop Increased central venous pressure (>16 cm H2O at right atrium) Circulation time ≥25 seconds Hepatojugular reflux Pulmonary edema, visceral congestion, or cardiomegaly at autopsy Minor Bilateral ankle edema Nocturnal cough Dyspnea on ordinary exertion Hepatomegaly Pleural effusion Decrease in vital capacity by one third from maximal value recorded Tachycardia (heart rate ≥120 beats/min) Major or minor Weight loss ≥4.5 kg in 5 days in response to treatment of heart failure *The diagnosis of heart failure requires that 2 major or 1 major and 2 minor criteria be present concurrently. Minor criteria were acceptable only if they could not be attributed to another medical condition. Patients who fulfill these criteria have an adverse prognosis regardless of the measured ejection fraction.
cases of HF found that survival at 3 months, 1 year, and 5 years was 86%, 76%, and 35%, respectively, and that survival was not significantly different for patients with diastolic HF vs systolic HF.6 This finding was later confirmed in 7 other small studies that analyzed survival in elderly patients with well-confirmed HF. Thus, when the diagnosis of HF in elderly patients is confirmed by Framingham criteria, prognosis may be similar in those with diastolic HF and systolic HF. Diseases that lead to systolic HF and diastolic HF are similar. Hypertension and coronary artery disease may manifest as isolated diastolic dysfunction or as combined systolic and diastolic dysfunction.3,6,8 Hypertrophic or restrictive cardiomyopathies and constrictive pericarditis are rare causes of diastolic HF, which may be more common in younger patients. Valvular disease can cause symptoms of HF in patients with a normal EF, and patients with severe valvular disease (moderate to severe or severe regurgitant or stenotic lesions of the mitral, tricuspid, and aortic valves) are not considered to have diastolic HF.9 Long-standing valvular disease can produce irreversible changes in left ventricular structure and myocardial function, which can manifest as diastolic dysfunction. Therefore, a patient who has new or
Mayo Clin Proc, October 2001, Vol 76
persistent symptoms and a normal EF after valve surgery with a normally functioning repair/replacement would be considered to have diastolic HF. A controversial theory is that the aging process is associated with altered diastolic function and that diastolic HF may develop in elderly patients in the absence of cardiovascular disease. HOW TO DIAGNOSE DIASTOLIC HF Diagnose HF An accurate diagnosis of the clinical syndrome of HF is the most crucial step in diagnosing diastolic HF. Dyspnea, exercise intolerance, and edema are common signs and symptoms but individually are not synonymous with HF because each can be caused by other conditions (deconditioning, pulmonary disease, obesity, venous disease, etc). Thus, the clinician must first determine whether the syndrome of HF is present. If the patient fulfills the Framingham criteria (Table 1), the diagnosis of HF is clear. In patients with suggestive but less severe symptoms, additional clinical information may enhance the suspicion of HF. The presence of cardiovascular disease (hypertension, coronary or previous [corrected] valvular disease) or risk factors for coronary artery disease strengthen the suspicion. The absence of lung disease on history, physical examination, chest radiography, or pulmonary function tests and the absence of tobacco use make a pulmonary etiology unlikely. Although some experts are reluctant to diagnose diastolic HF in the presence of lung disease, lung disease related to smoking is extremely common, and such patients frequently have concomitant obstructive lung disease and systolic HF. Thus, a diagnosis of lung disease should not exclude diastolic HF if clear-cut signs and symptoms of HF are present. The response to diuretics is often helpful in confirming concomitant HF in such patients. If a patient was previously active and has experienced a sudden or subacute reduction in exercise tolerance, deconditioning is not a likely explanation for the patient’s symptoms. Anemia, thyroid dysfunction, or other systemic disease can be excluded by findings on clinical examination and basic testing. However, anemia and infection commonly precipitate episodes of HF in patients with underlying ventricular dysfunction. Thus, the presence of these conditions does not exclude concomitant HF. An important feature of symptoms related to HF is that the symptoms improve with diuretics. Thus, a patient’s response to diuretics is part of the Framingham criteria, and improvement of symptoms (other than edema alone) after a trial of diuretics is highly suggestive of HF. Determine Whether Systolic Dysfunction is Present Early hospital-based studies confirmed that clinical features and physical examination findings fail to distinguish
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Mayo Clin Proc, October 2001, Vol 76
systolic HF from diastolic HF.5 Community-based studies also revealed that no clinical characteristics reliably identified patients with normal systolic function. Although advanced age, history of hypertension, female sex, and absence of myocardial infarction were associated with preserved EF, these features were often present in patients with systolic HF, and neither these features nor New York Heart Association class or chest x-ray films were helpful to distinguish systolic HF from diastolic HF. Guidelines from the American College of Cardiology/American Heart Association recommend echocardiography in all patients with suspected HF.10 Echocardiography should be performed while the patient is symptomatic (before treatment) if possible. If EF is reduced substantially (<40%), the patient should receive standard therapy for systolic HF, as established by clinical trials and summarized in numerous reviews and position papers, with angiotensin-converting enzyme (ACE) inhibitors, β-blockers, digoxin, and diuretics as needed to control symptoms.10,11 Patients with “borderline” systolic function (EF, 40%-50%) should be considered individually. The clinician may want to consider assessing EF with an alternative modality. If EF is only mildly impaired, the clinician should consider the diagnosis of diastolic HF. Can Diastolic HF Be Diagnosed Confidently If EF is Normal? Although the “working definition” of diastolic HF in most studies published to date has been clinical HF with normal EF, details of the definition of diastolic HF have varied substantially. Disagreement exists over what should be considered a “normal” EF, how soon the EF must be assessed after HF has been diagnosed, and whether measurement of hemodynamics or other tests for the presence of diastolic dysfunction must be performed. Recently, 2 different standardized diagnostic criteria for diastolic HF were suggested. The European criteria suggest that a patient not only have HF with a normal EF (defined as >45%) but also some objective quantification (Doppler echocardiography or invasive hemodynamics) of diastolic dysfunction.12 The criteria suggested by Vasan and Levy9 require a more stringent definition of a normal EF (>50%) and necessitate invasive hemodynamic data to confirm definite diastolic HF. Classification as probable or possible diastolic HF is based on proximity of the EF determination to the patient’s symptoms (<3 days for probable and >3 days for possible) and on supportive clinical features. Although these criteria are helpful, they are as yet untested in their ability to identify patients with an adverse prognosis who might respond to a standardized treatment approach. Commonsense guidelines for diagnosing diastolic HF are summarized in Table 2. Patients who have suggestive symptoms but do not fulfill Framingham criteria for HF
Heart Failure and Normal Ejection Fraction
1049
Table 2. Clinical Features Suggestive of Diastolic Heart Failure* Fulfillment of Framingham criteria for HF Ejection fraction >50% while the patient is symptomatic or soon (3 days) after initial treatment Consistent clinical scenario Elderly patient (especially female) History of hypertension Hypertension at presentation Recent onset of tachyarrhythmia coincident with HF episode Coronary disease without previous myocardial infarction or Q waves HF not explained by presence of uncorrected valvular disease *HF = heart failure.
must be considered individually, and patients who fit the typical profile may be more likely to have HF and should be offered a trial of HF treatment if they have no noncardiac reason for their symptoms. Although prompt assessment of systolic function is recommended, a recent study suggested that EF measured during an episode of hypertensive pulmonary edema is similar to that measured within 1 to 3 days after the acute episode.13 Certain clinical features are common among patients with diastolic HF. Approximately 30% of patients with diastolic HF present with recent-onset atrial fibrillation or flutter.6,14 Patients with underlying diastolic dysfunction rely on “atrial kick” to maintain filling with normal mean atrial pressures. Loss of atrial kick and tachycardia often present with newonset atrial fibrillation result in the need for higher atrial pressures to maintain filling in the presence of underlying diastolic dysfunction and may precipitate HF. Likewise, worsening diastolic function and chronic elevation in left atrial pressures may precipitate onset of atrial fibrillation. Many patients with diastolic HF have hypertension at presentation. Although poorly controlled hypertension can precipitate an HF episode in patients with systolic dysfunction, it is particularly common among patients with diastolic HF. Finally, ischemia may worsen diastolic function without decreasing EF. Thus, patients presenting with ischemia may have diastolic HF. Does Diastolic Function Need To Be Measured? Noninvasive assessment of diastolic function has advanced considerably in recent years, and Doppler echocardiography can evaluate diastolic function and detect the presence of increased filling pressures in most patients.2,15,16 However, skilled and informed assessment of diastolic function is not yet standard in all echocardiographic laboratories. Indeed, many erroneous statements may be made concerning diastolic function when assessment is incomplete. If an echocardiography laboratory can provide a comprehensive assessment of diastolic function that does
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
1050
Heart Failure and Normal Ejection Fraction
Table 3. Treatment of Diastolic Heart Failure* Improve acute symptoms Diuretics Treat precipitating factors and underlying disease Hypertension: diuretics, β-blockers, ACE inhibitors, ARB, calcium channel blockers Ischemia: β-blockers, calcium channel blockers, nitrates, revascularization Atrial arrhythmia Control heart rate: β-blockers, calcium channel blockers, digoxin Maintain sinus rhythm: cardioversion, antiarrhythmics Prevent emboli: warfarin Improve survival ? β-Blockers ? ACE inhibitors Prevent relapse into symptomatic HF by intensifying outpatient follow-up Control blood pressure Provide dietary counseling (sodium) Monitor volume status (daily weights, diuretic adjustment) Maintain normal sinus rhythm Institute exercise program *ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blockers; HF = heart failure.
not rely solely on the mitral inflow pattern, confirmation of abnormal diastolic function can strengthen the diagnosis of diastolic HF. However, diastolic function may not be assessed or may be interpreted improperly. Laboratory personnel who rely only on the mitral inflow signal to characterize diastolic function may report that diastolic function is normal, but numerous studies have shown that the mitral inflow pattern may be “pseudonormal” in the presence of substantially elevated atrial pressures.15 Doppler echocardiographic assessment of diastolic function was reviewed recently.2 If the patient has clear-cut HF and a normal EF, these criteria should influence diagnosis and treatment. Some simple echocardiographic criteria may be helpful in the absence of a comprehensive diastolic assessment. Left atrial enlargement often reflects long-standing elevation of atrial pressures, and its presence supports the diagnosis of diastolic HF. Left ventricular hypertrophy, although not invariably present, also supports the diagnosis because of its association with diastolic dysfunction. Elevated right-sided diastolic pressures in the absence of pulmonary vascular disease can be detected by measuring the tricuspid regurgitant velocity, and such pressures support the diagnosis of elevated left-sided diastolic pressures. A wall motion abnormality in the absence of a reduction in global systolic function also supports the diagnosis of diastolic HF. TREATING DIASTOLIC HF The best current strategy for patients with diastolic HF is to treat the underlying etiologies (hypertension, coronary ar-
Mayo Clin Proc, October 2001, Vol 76
tery disease) and the precipitating factors (labile hypertension, ischemia, tachyarrhythmias). Therapy for diastolic HF (Table 3) should target 4 goals: provide symptomatic relief, treat underlying disease and precipitating factors, improve survival, and reduce other adverse outcomes (rehospitalization). Diuretics When a patient has evidence of venous congestion, the most direct treatment is diuretics. Caution must be used because some patients with diastolic HF are sensitive to the preload reduction and may develop hypotension or severe prerenal azotemia. Diuretics have also been proved to control blood pressure and to reverse left ventricular hypertrophy. Although the need for maintenance therapy with diuretics must be assessed in each patient, the patient with acute symptoms requires diuretics, and most patients with severe diastolic HF require some maintenance therapy. Intravenous agents should be used for acute symptoms. Long-term oral dosing should be adjusted to maintain a patient’s weight at the time the symptoms were controlled, based on daily weights. Nitrates Nitrates may be useful because of their preload-reducing and anti-ischemic effects.10 Indeed, the Vasodilator Heart Failure Trial showed a trend toward better survival among patients with HF and an EF greater than 45% who received isosorbide dinitrate plus hydralazine.17 Dosing as for coronary artery disease is appropriate. Calcium Channel Blockers Calcium channel blockers are well known for their antihypertensive, anti-ischemic, and negative chronotropic effects and can be helpful. A small placebo-controlled, double-blinded, 5-week crossover trial showed that verapamil improved exercise capacity and HF score.18 This improvement occurred with a decrease in heart rate but with no change in blood pressure compared with baseline or placebo. Although calcium channel blockers do not immediately improve diastolic function when initially administered,19 these drugs are useful to treat conditions that precipitate diastolic HF (hypertension and ischemia). Dosing should be targeted at controlling blood pressure and angina. Angiotensin II Receptor Blockers and ACE Inhibitors Angiotensin II receptor blockers and ACE inhibitors can be used for their antihypertensive effect. In patients known to have diastolic dysfunction and a hypertensive response to exercise, losartan improved exercise time, quality of life, and exercise systolic blood pressure.20 A
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Mayo Clin Proc, October 2001, Vol 76
meta-analysis suggested that ACE inhibitors have the strongest effect on regression of left ventricular hypertrophy, and thus they may improve diastolic function via their antihypertrophic effect. In patients with diastolic HF and prior myocardial infarction, enalapril improved New York Heart Association function class and treadmill exercise duration compared to placebo.21 Two retrospective studies showed that survival was associated with ACE inhibitor therapy in patients with diastolic HF.22,23 In these retrospective studies, ACE inhibitors were likely used to treat hypertension rather than HF per se. Prospective trials are needed to evaluate the effectiveness of angiotensin II receptor blockers and ACE inhibitors in diastolic HF. Until then, dosing should be targeted at controlling blood pressure. β-Blockers β-Blockers can be used to control hypertension, ischemia, and tachycardia and thus may be useful in patients with diastolic HF associated with these factors. A retrospective study showed that β-blockers were independently associated with improved survival in patients with diastolic HF.22 β-Blockers do not improve diastolic function immediately but may result in long-term improvement analogous to their effect on systolic function in patients with systolic HF.24 Currently, β-blockers should be used to treat underlying disease as their benefit for diastolic HF per se is unproved. Thus, dosing would be as needed for control of blood pressure and ischemic symptoms.
Heart Failure and Normal Ejection Fraction
REFERENCES 1. 2. 3.
4. 5. 6. 7.
8. 9. 10.
11.
12. 13.
Digoxin Digoxin is not recommended specifically for diastolic HF and can be deleterious in certain situations (hypertrophic cardiomyopathy). In patients with diastolic HF and atrial arrhythmia, digoxin may be needed to control heart rate. Recommendations Recommendations for the therapeutic approach to the patient with diastolic HF are summarized in Table 3. Unfortunately, most clinical trials to date have focused exclusively on patients with HF and systolic dysfunction. Only recently have trials been undertaken to address the potential benefit of medical treatment of diastolic HF. Until the results of such trials are available, aggressive treatment of the underlying disease and precipitating factors and close outpatient follow-up after the diagnosis is made remain the only treatment approach available for the patient with diastolic HF. Finally, aggressive treatment of blood pressure has been documented to prevent HF,25 and because hypertension is the most common factor leading to diastolic HF, the importance of prevention of diastolic HF through aggressive management of hypertension cannot be overemphasized.
1051
14.
15. 16.
17. 18.
19. 20.
21.
Brutsaert DL, Sys SU. Diastolic dysfunction in heart failure. J Card Fail. 1997;3:225-242. Lainchbury JG, Redfield MM. Doppler echocardiographic-guided diagnosis and therapy of heart failure. Curr Cardiol Rep. 1999; 1:55-66. Vasan RS, Larson MG, Benjamin EJ, Evans JC, Reiss CK, Levy D. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort. J Am Coll Cardiol. 1999;33:1948-1955. Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation. 1993;88:107-115. Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol. 1995;26:1565-1574. Senni M, Tribouilloy CM, Rodeheffer RJ, et al. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation. 1998;98:2282-2289. Kitzman DW, Gardin JM, Arnold A, et al, CHS Reseach Group. Heart failure with preserved systolic LV function in the elderly: clinical and echocardiographic correlates from the Cardiovascular Health Study [abstract]. Circulation. 1996;94(suppl 1):I-433. Abstract 2528. Vasan RS, Levy D. The role of hypertension in the pathogenesis of heart failure: a clinical mechanistic overview. Arch Intern Med. 1996;156:1789-1796. Vasan RS, Levy D. Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation. 2000;101:2118-2121. Guidelines for the evaluation and management of heart failure: report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). Circulation. 1995;92:2764-2784. Consensus recommendations for the management of chronic heart failure: on behalf of the membership of the Advisory Council To Improve Outcomes Nationwide in Heart Failure. Am J Cardiol. 1999;83(2A):1A-38A. European Study Group on Diastolic Heart Failure. How to diagnose diastolic heart failure. Eur Heart J. 1998;19:990-1003. Gandhi SK, Powers JC, Nomeir A-M, et al. The pathogenesis of acute pulmonary edema associated with hypertension. N Engl J Med. 2001;344:17-22. Chen HH, Lainchbury JG, Senni M, Redfield MM. Diastolic heart failure in the community: underlying cardiovascular diseases and precipitating factors [abstract]. Circulation. 2000;102(suppl 2):II780. Abstract 3769. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician’s Rosetta Stone. J Am Coll Cardiol. 1997;30:8-18. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation. 2000;102:17881794. Cohn JN, Johnson G, Veterans Administration Cooperative Study Group. Heart failure with normal ejection fraction: the V-HeFT Study. Circulation. 1990;81(2, suppl):III48-III53. Setaro JF, Zaret BL, Schulman DS, Black HR, Soufer R. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Am J Cardiol. 1990;66:981-986. Nishimura RA, Schwartz RS, Holmes DR Jr, Tajik AJ. Failure of calcium channel blockers to improve ventricular relaxation in humans. J Am Coll Cardiol. 1993;21:182-188. Warner JG Jr, Metzger DC, Kitzman DW, Wesley DJ, Little WC. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. J Am Coll Cardiol. 1999;33:1567-1572. Aronow WS, Kronzon I. Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fraction. Am J Cardiol. 1993;71:602-604.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
1052
22.
23.
24. 25.
Heart Failure and Normal Ejection Fraction
Chen HH, Lainchbury JG, Redfield MM. Factors influencing survival in patients with diastolic heart failure in Olmsted County, MN in 1996-97 [abstract]. Circulation. 2000;102(suppl 2):II-412. Abstract 2006. Philbin EF, Rocco TA Jr, Lindenmuth NW, Jenkins PL. Angiotensin-converting enzyme inhibitor use in diastolic heart failure is associated with a reduced risk of death [abstract]. J Am Coll Cardiol. 2000;35(suppl A):232A. Abstract 1010-172. Eichhorn EJ, Bristow MR. Medical therapy can improve the biological properties of the chronically failing heart: a new era in the treatment of heart failure. Circulation. 1996;94:2285-2296. Kostis JB, Davis BR, Cutler J, et al, SHEP Cooperative Research Group. Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA. 1997;278:212-216.
Questions About Patients With HF and Normal EF
Mayo Clin Proc, October 2001, Vol 76
b.
c.
1. Which one of the following is true? a. Patients with HF and reduced EF are usually more symptomatic than patients with diastolic HF b. Patients presenting with severe hypertension and HF symptoms are unlikely to have a normal EF c. Patients with diastolic HF are less likely to have jugular vein distention and a third heart sound compared with those who have HF and reduced EF d. Patients with underlying diastolic dysfunction are likely to develop HF with onset of atrial fibrillation e. Patients with new-onset diastolic HF could not have experienced myocardial infarction in the past 2. Which one of the following most commonly causes diastolic HF? a. Hypertrophic cardiomyopathy b. Constrictive pericarditis c. Hypertension alone or concomitant with coronary artery disease d. Amyloid heart disease e. Valvular heart disease 3. Which one of the following is true when echocardiography in a patient with HF reveals a normal EF (>50%)? a. EF was probably lower at initial patient presentation b. Presence of left atrial enlargement supports diagnosis of diastolic HF c. Presence of wall motion abnormalities precludes diagnosis of diastolic HF d. Absence of left ventricular hypertrophy precludes diagnosis of diastolic HF e. “Normal” mitral inflow pattern precludes diagnosis of diastolic HF 4. Which one of the following patients is most likely to have diastolic HF? a. A 65-year-old sedentary woman with no history of hypertension, coronary artery disease, diabetes mellitus, or smoking but with known venous insufficiency presents with edema, exertional
d.
e.
dyspnea, and fatigue without paroxysmal nocturnal dyspnea, orthopnea, or exertional dyspnea. Chest radiography shows normal heart size and no evidence of pulmonary venous hypertension. An 85-year-old woman with a long history of poorly controlled systolic hypertension presents with a 1week history of tachypalpitations, progressive dyspnea, paroxysmal nocturnal dyspnea, orthopnea, and edema. Her blood pressure is 198/85 mm Hg on admission. Chest radiography shows cardiomegaly and pulmonary venous hypertension. Electrocardiography reveals atrial fibrillation with rapid ventricular response, voltage criteria for left ventricular hypertrophy, and no Q waves. A 53-year-old man with previous myocardial infarction but no known HF presents with a 3-week history of exertional dyspnea, orthopnea, fatigue, and edema. Chest radiography shows cardiomegaly and pulmonary venous hypertension. Electrocardiography reveals Q waves in leads V1 through V5. A 72-year-old man with severe obstructive lung disease presents with worsening dyspnea. He has no history of hypertension or coronary artery disease. Chest radiography shows normal heart size, hyperinflation with flattened diaphragms, and emphysematous changes most prominent in the upper lung fields. Electrocardiography reveals low anterior forces. A trial of diuretics results in no improvement in dyspnea. A 70-year-old woman known to have metastatic colon cancer was admitted to the hospital for right hip arthroplasty. One week after discharge the patient noted new-onset dyspnea on exertion. She has no history of hypertension or coronary artery disease. Chest radiography shows normal heart size, and electrocardiography reveals sinus tachycardia.
5. Which one of the following is false concerning treatment of diastolic HF? a. No prospective randomized clinical trial has yet shown that β-blockers and ACE inhibitors improve survival in patients with diastolic HF b. β-Blockers should not be used for diastolic HF because they have not been shown to improve acute symptoms of diastolic dysfunction c. Diuretics and nitrates are useful to control fluid overload states in patients with diastolic HF d. Digoxin can be used in patients with diastolic HF and atrial fibrillation e. Restoration and maintenance of sinus rhythm may improve symptoms in patients who present with new-onset atrial fibrillation, HF, and a normal EF
Correct answers: 1. d, 2. c, 3. b, 4. b, 5. b
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.