Epidemiology of congestive heart failure

Epidemiology

of Congestive Heart Failure THOMAS

KILLIP, MD

The incidence of congestive heart failure (CHF) is influenced by a variety of factors, including availability of medical care, socioeconomic status, geography, nutrition and race. The etiology of CHF in China, England, Botswana and Sweden will be examined and compared with prospective findings

from Boston and Detroit. Because the therapy used in the treatment of CHF varies with the underlying causes, which may be as diverse as rheumatic fever, systemic hypertension and viral infection, the importance of fully determining its pathogenesis is emphasized. (Am J Cardtol 1985;56:2A-6A)

Congestive heart failure (CHF) is a common clinical manifestation associated with many different forms of heart disease. It is encountered frequently by the practitioner on his daily rounds. Although the symptoms may be of acute onset, in most cases CHF reflects longstanding albeit slowly progressive heart disease, which may have gone unrecognized by both patient and physician. Because heart disease is the leading cause of death in the Western world and the terminal event frequently occurs in the setting of chronic CHF, its importance in contributing to morbidity and mortality cannot be overemphasized. Definition: The frequent textbook definition’-that CHF occurs when the ventricle is unable to provide a cardiac output to meet the metabolic demands of the body-is not particularly useful to the clinician. In most patients, the clinician recognizes CHF by the manifestations of congestion, not by recognition of a low cardiac output. Indeed in certain circumstances, gradual reduction of cardiac output over many months or years may be surprisingly well tolerated by the patient with slowly progressive CHF. A more satisfactory clinical definition of CHF focuses on the phenomena of congestion. Thus, for the purposes of this article, CHF is defined as a clinical syndrome characterized by congestion of the pulmonary or systemic circulation owing to increase in pulmonary venous or systemic venous pressure to the level of plasma protein oncotic pressure

or above. Other noncardiac causes of congestion are usually readily distinguished by the clinician. The manifestations of CHF are largely due to changes in compliance in the venous circuit accompanied by transudation of fluid. Increased venous pressure may reflect disease of the atrium or obstruction of the atrioventricular valve, as in mitral stenosis, or alterations in ventricular filling pressure and ventricular stiffness as a direct expression of myocardial abnormality. In the past much attention has been devoted to a discussion of forward and backward ventricular failure. Severe forward failure manifests itself as cardiogenic shock. Lesser degrees of forward failure contribute to the perfusion deficiency during exercise, but this abnormality is not as readily recognized by the clinician. In the discussion that follows the emphasis will be on the congestive aspects of heart failure. However, as shown by Starr,2l3 the congestion of right-sided CHF depends on retention of sodium by the kidney, which occurs whether the right or the left ventricle is diseased. The stimulus for sodium retention has not been fully explained. Either or both ventricles may fail. While the most common cause of right ventricular failure is left ventricular (LV) failure, the right ventricle may fail independently as in car pulmonale. Right ventricular failure is much less common than LV failure and most of this article will focus on the latter. Evaluation of the patient: Recent emphasis on the problem-oriented approach to clinical record keeping has led some younger physicians to the erroneous assumption that recognition of the problem, in contrast to understanding causality, is sufficient for planning effective therapy. In a teaching hospital, one commonly encounters completed medical records in which the principal diagnosis is CHF with no statement of etiol-

From the Department of Medicine, Beth Israel Medical Center, New York, New York. Address for reprints: Thomas Killip, MD, Department of Medicine, Beth Israel Medical Center, 10 Nathan D. Perlman Place, New York, New York 10003.

2A

July

ogy, mechanism or precipitating factors. A thoughtful analysis of the problem is lacking because appropriate management of CHF requires a full understanding of the pathogenesis of the heart disease. Clinical evaluation of the patient with CHF properly encompasses 4 factors: etiology or structural cause; fundamental mechanism inducing CHF; acute precipitating factors; and functional capacity. Determination of the functional capacity at each patient encounter is exceedingly important in following the effectiveness of therapy, but this aspect will not be discussed further because most physicians are quite familiar with the classification of the New York Heart Association (NYHA). Examples of the approach just outlined follow. A young woman is admitted to the hospital with acute pulmonary edema. She is anemic and has had recent onset of rapid atria1 fibrillation. Following evaluation it is apparent that she has rheumatic heart disease and mitral stenosis with moderate valvular obstruction. During the past several months, she has had severe menorrhagia secondary to uterine fibroids. In this instance an appropriate classification would be acute pulmonary edema secondary to rheumatic heart disease with moderate mitral stenosis and severe pulmonary venous hypertension aggravated by anemia and recent onset of atria1 fibrillation. A second example is a 72-year-old man admitted with progressive shortness of breath and weight gain. He has had 2 myocardial infarctions in the past but had functioned well until the recent development of rather severe hypertension. In addition to the evidence of heart failure, careful physical examination reveals elevated systolic and diastolic pressure, and a bruit in the left flank. A final evaluation indicates that the patient has CHF owing to coronary artery disease with abnormal ventricular function secondary to the scars of multiple old myocardial infarcts. The precipitating factor was the development of an atherosclerotic renal arterial occlusion with secondary severe hypertension. A third example is a 34-year-old man who enters with severe shortness of breath, abdominal swelling and peripheral edema 1 week after the marriage of a cousin. He had been known to have an enlarged heart for at least 4 years but had been functioning reasonably well. No cause of the cardiomyopathy could be recognized. At the recent wedding reception, he had drunk excessively of champagne and had gorged.himself on caviar, herring and pretzels. Thus, this patient had CHF due to dilated cardiomyopathy of unknown cause, possibly viral, with a progressive reduction in myocardial contractility secondary to diffuse sarcomere microscopic damage and probable progressive loss of adrenergic receptors. The precipitating factors were an acute salt and fluid overload. Each of these patients was NYHA functional class IV on admission. Appropriate treatment led to considerable improvement. In each case an adequate understanding of the etiology, mechanism and precipating factors for the CHF was necessary for optimal shortand long-term therapy.

10, 1985

THE

AMERICAN

JOURNAL

OF CARDIOLOGY

Volume

56

3A

ailure Desired

Therapeutic

Improved myocardial Diuretic Correct potassium Arrhythmia Vasodilator

Effect

function

44% 33% 7% 2% 1%

Epidemiology The incidence of CHF is influenced by a variety of factors, including availability of medical care, socioeconomic status and geography. Epidemiologic studies suggest an incidence of between 0.5 and 2 cases/l,000 patient visits in the United States.* Other clinical estimates suggest a higher figure of 3.8 cases/l,000 patient. visits.5 Data from the National Disease and Therapeutic Index nrovide important information on patient and physician contacts in the United States.” A sample of office-based physicians are surveyed quarterly and the results extrapolated for the country as a whole. Of the 1.252 billion physician-patient contacts in 1983, 72% were in the office and 18% in the hospital. Of the 10.935 million physician-patient contacts for congestive heart failure in 1983,49% were in hospital and 41% in office. The house call has not completely vanished: 2% or 220,000 contacts were via this route. Of patients with CHF, 42% were seen by internists, 31% by family practitioners and 14% by cardiologists. The desired therapeutic result was to improve myocardial function in 44%, to produce diuresis in 33% and to correct potassium imbalance in 7%. Control of arrhythmia or vasodilation was desired in 2 and 1% of contacts, respectively. Therapy received during physician-patient contacts for CHF reflected these goals (Table I). Digitalis preparations were given in 67%, diuretics in 59% and vasodilators, antihypertensives or an angiotensin converting enzyme inhibitor in less than 10% of encounters. The etiology of CHF also varies according to geographic location, socioeconomic status, economic standard of the region and race. Nutritional forms of heart disease are uncommon in the Western world, but are clearly a significant cause of CHF in developing countries.7 For example, in certain provinces of China, CHF due to selenium deficiency, termed Keshan disease and perhaps related to many millennia of farming, is a frequently recognized condition.8 Myocardiopathy appears to be more common than other forms of heart disease in certain developing countries. It is said that myocardiopathy of unknown cause postulated to be secondary to viral infections is commonly encountered in the countryside, but is rare in the cities in China (personal communication from the cardiology faculty of Beijing Medical College). A high incidence of myocardiopathy was encountered by Edmunds in Botswana.g Rheumatic heart disease is a major health problem in developing countries but has become progressively

A SYMPOSIUM:

4A

TABLE

II

ROLE OF NITRATES

Heart Failure Cases)

in Botswana

IN CONGESTIVE

HEART FAILURE

(131 Consecutive

TABLE

IV

100 Consecutive Discharges of Congestive Heart Failure from Henry Ford Hospital (1963)

Percent Rheumatic Myocardiopathy Congenital Hypertension Viral Pericarditis Miscellaneous From

TABLE

45 24 9 E 4 5

reference

Ill

Hypertension Hypertension CAD present RHD present

9.

Epidemiology of Congestive Heart Failure (CHF) in the Framlngham Study (1949-1966) most common precursor preceded CHF in 75 % in 59 % ; with hypertension in 21%, with hypertension

From reference CAD = coronary

12. artery

disease;

Percent Hypertension Coronary artery disease Diabetes mellitus Valvular heart disease Rheumatic-6 of 16 cases Renal failure Cardiomyopathy Alcohol abuse-4 of 6 cases Unknown cause

TABLE V

RHD = rheumatic

Coronary artery disease With hypertension gt ;iEtes mellitus heart disease.

less common in the Western world (Table II). This appears to be due to 2 factors. Health statistics from England document that the incidence of rheumatic fever has been declining since at least 189O.‘O More recent data suggest that the incidence and severity of rheumatic fever after streptococcal sore throat have also declined remarkably. I1 Although valvular heart disease is a common cause of CHF in this country, most newly recognized cases are probably not rheumatic. The Framingham study evaluated the incidence of CHF prospectively (Table III).12 Of 142 new cases of CHF detected between 1949 and 1966, hypertension was the most common precursor, occurring in 75% of the patients before the onset of CHF. Coronary artery disease (CAD) was recognized in 39%, with accompanying systemic hypertension in 29%. Rheumatic heart disease preceded CHF in 21%; systemic hypertension was associated in 11%. Furthermore, the observations demonstrated that CHF has a poor prognosis. The probability of patients with new onset of CHF dying in 5 years was 62% for men and 42% for women. The Framingham study has made an important contribution to our understanding of the epidemiology of CHF. However, the observations published in 1971 are based on data accumulated between 1949 and 1966. These data may now be as old as 36 years. Although systemic hypertension is recognized as a frequent accompaniment of CHF, it is far from clear that it is the precipitating factor in as high a percentage of cases as noted in the Framingham study. It is known that a significant increase in peripheral vascular resistance of reflex origin is a frequent accompaniment of progressive cardiac disability with CHF. What physician has not encountered the patient with acute pulmonary edema struggling desperately to breathe who has cool, pale, cold extremities and profuse diaphoresis suggesting a shock-like picture, only to find systemic hypertension, not hypotension, upon measurement of blood pressure? In the example cited, although peripheral perfusion is obviously sharply curtailed, reflex alterations in vas-

Ef 16 10 6 19

100 Consecutive Discharges of Congestive Heart Failure from Henry Ford Hospital (1963)

of CHF in 29 % in 11%

31

No.

Percent

26

100 35 23 15

6” 4

cular resistance result in striking elevations of arterial pressure. In many instances of CHF it is difficult to determine whether the elevated blood pressure is secondary to myocardial failure or causal, or both. Recently, 100 consecutive patients discharged from Henry Ford Hospital with a diagnosis of CHF were reviewed (Tables IV and V; Killip T., unpublished observations). Systemic hypertension was found in 31%, CAD in 26% and valvular heart disease in 16%. Only 6 of the 16 patients with valvular heart disease, however, were deemed rheumatic. Thus, systemic hypertension was common but was not found in most patients. Diabetes mellitus occurred in 25%. Of the patients with CAD, 35% had associated systemic hypertension, 23% had associated diabetes mellitus and 15% had both. It is clear that diabetes mellitus is an important contributing factor in the pathogenesis of myocardial disease leading to CHF. This problem is likely to increase as our population ages. Renal failure was recognized as the primary cause of CHF in 10% of cases. This incidence may reflect the fact that this institution has a renal center with a large was transplant program. Dilated cardiomyopathy identified in 6 patients with a discharge diagnosis of CHF, ascribed to alcohol abuse in 4 and of unknown cause in 2. No cause was recognized for the CHF in 19 patients at discharge. Dilated cardiomyopathy is an uncommon cause of CHF. In a 1978 study from Malmo, Sweden, Tarp’s reviewed all cases of suspected myocardial disease over an s-year period (Tables VI and VII). One hundred and seventy-four severely symptomatic patients were investigated further and in 59 patients, dilated cardiomyopathy was recognized as the cause. During the same period, dilated cardiomyopathy was found at autopsy in an additional 35 cases. Torp’s study is of considerable interest because the population in Malmo is stable at approximately 250,000 and medical care is provided in a small number of institutions. Torp calculated the incidence of cardiomyopathy as 3 new clinical cases/l,000

July

TABLE

VI

Congestive (8 Years)

Cardiomyopathy

(CCM)

in Malmo

Population 250,000 500 cases of suspected myocardial disease 174 severe cases 59 cases of CCM plus 35 autopsies 115 other causes 94 cases of verified CCM From reference 13.

population/year, while the frequency was approximately 5 cases/lOO,OOO/year. Thus, although dilated cardiomyopathy is an important clinical challenge for accurate diagnosis and effective treatment, it represents a small fraction of patients presenting with CHF. It has been recognized in recent years that CAD may give rise to cardiomyopathy in the absence of recurrent ischemic symptoms or evidence of old myocardial infarction. The cardiomyopathic syndrome caused by CAD is usually associated with recurrent ischemia, ventricular septal rupture or ventricular aneurysm and thus is readily recognized clinically. In a prospective study at Massachusetts General Hospital, Boucher et all4 investigated a group of patients with CAD cardiomyopathy to determine why the condition may go undetected clinically. The medical records of all patients with CHF were reviewed and a clinical cause assigned. Ninety consecutive autopsies were performed in patients with CHF. In 15 the cause was not clinically apparent. Valvular heart disease was the most common cause confirmed at autopsy, occurring in 45%, although one-third had associated CAD. Clinically recognized CAD occurred in 20 cases. The cause of CHF was unexplained in 15 patients. Autopsy revealed CAD in 7, cardiomyopathy in 5 and valvular heart disease in 3. Of the patients with unexplained CHF, 6 had diabetes mellitus; 5 of the diabetics also had CAD. The patients with CAD cardiomyopathy unrecognized clinically had multiple subendocardial myocardial infarctions. Only 1 patient had a transmural infarction, and* that was posterior. The investigators concluded that patients with CAD cardiomyopathy that is difficult to recognize clinically often have diabetes mellitus and lack recurrent episodes of myocardial ischemia, but suffer from multiple nontransmural myocardial infarcts.14 Treatment The principles of treatment for CHF are well known to all clinicians. Three therapeutic approaches, singly or combined, are currently utilized: digitalis, diuretics and vasodilators.15 Although clinical experience strongly suggests that in many instances aggressive treatment improves prognosis, careful detailed studies confirming this impression are few. The recent development of vasodilator therapy to reduce ventricular filling pressure, aortic impedance and ventricular work has led to a vigorous reexamination of the effect of treatment on outcome in CHF.r6J7 The effectiveness of digitalis remains controversial. The inotropic effects of digitalis are modest and appear to be most effective when enddiastolic volume is increased.r8 The important addi-

30, 4985

THE

AMERICAN

JOURNAL

ongestiwe Population Cases CCM in 8 years Clinical Incidence Autopsy Frequency

OF CARDIOLOGY

iomyopath

Volume

) in

5%

56

atmo

250,000

59 3 casest105tyear 35 cases CGM 5 cases CCMt1Q5t

year

From reference 13.

tional effects of the drug to reduce the incidence of supraventricular arrhythmia and slow the ventricular rate in atria1 fibrillation are also useful. It is important to recognize that the British have taught that digitalis is effective primarily in the presence of atria1 fibrillation. The effects on renal blood flow may also be modestly beneficial. WitheringI believed that the therapeutic effect of foxglove was secondary to its diuretic properties. Although there has been great interest in the development of new inotropic agents, none is yet available for other than experimental use. The noncatecholamine, nonglycoside inotropic drugs amrinone and milrinone have attracted considerable attention. Most extensive clinical experience has been with amrinone, which produces significant hemodynamic benefits and improves exercise tolerance in many patients with severe CHF.20 Maintenance doses are highly variable, and there is a high incidence of adverse effects, including a potentially troublesome decrease in platelets. A recent report21 suggests that long-term administration of the drug may also be associated with progressive decline in ventricular function. Diuretics remain the mainstay of effective therapy of CHF. Many patients may be treated satisfactorily with a diuretic alone. Rader et a122 demonstrated that digitalis did not further improve cardiac function in a cohort of patients treated adequately with diuretics for CHF. Because diuresis lowers ventricular filling pressure, reduces congestion and improves ventricular function, it is not surprising that digitalis may not add to the clinical effect in selected patients. The most significant improvement in the management of patients with CHF in decades has been the recognition that the decrease in venous and arterial tone, ventricular filling pressure, aortic impedance and cardiac work with appropriate use of vasodilator therapy improves cardiac function and exercise tolerance.16J7123224 Current debate has focused on the optimal choice of therapeutic agents, and whether or not vasodilator therapy improves long-term prognosis.25 Studies have been carried out using isosorbide dinitrate, hydralazine, minoxidil, prazosin and captopril.25 Double-blind placebo-controlled studies with isosorbide dinitrate26,27 and with captopril, an orally administered inhibitor of angiotensin converting enzyme, have demonstrated clinical and hemodynamic benefits.28>2g Exercise tolerance may be improved by effective vasodilator therapy and the degree of improvement may not necessarily be predicted from the initial hemodynamic response to the drug. Congestive heart failure is a common clinical problem. It is often the first manifestation of longstanding

6A

A SYMPOSIUM:

ROLE

OF NITRATES

IN CONGESTIVE

HEART

FAILURE

heart disease and adversely affects prognosis. Systemic hypertension, CAD and valvular heart disease are the most common causes of CHF currently encountered. Diabetes mellitus is a frequently associated condition, especially in patients with systemic hypertension or CAD. Systemic hypertension is probably less frequently a cause of CHF than a coexisting or precipitating factor. Clinically unrecognized cardiomyopathy secondary to CAD is characterized by absence of ischemia, a high incidence of diabetes mellitus and multiple nontransmural myocardial infarcts. During the past decade, vasodilator therapy has been added to the 2 mainstays of treatment: digitalis and diuretics. Although the availability of safe and highly effective newer inotropic drugs is awaited with interest, none is yet available for widespread clinical use. Vasodilator therapy improves resting hemodynamics and exercise tolerance. A wide variety of agents has been evaluated for use as vasodilators. Nitrates, hydralazine and captopril have gained the widest acceptance and the greatest experience and are clearly effective. The identification of responders or nonresponders to a particular drug or combinations of drugs and well-designed studies to test the effects of vasodilator therapy on long-term prognosis will be important future advances. References 1. Wood PW. Diseases of tha Heart and Circulation. 2nd ed. Philadelphia: Lippincott. 1956:264. 2. Starr I, Rawaon AJ. Role of the ‘static blood pressure’ in abnormal increments of venous pressure, especially in heart failure. I. Theoretical studies on an improved circulation scheme whose pumps obey Starling’s law of the heart. Am J Med Sci 1940;199:27-39. 3. Starr I. Role of the static blood presslre in abnormal increments of venous pressure especially in heart failure. II. Clinical and experimental studies. Am J Med Sci 1940; 199:40-55. Klainer LM, Gibson TC, Whtte KL The epidemiology of cardiac failure. J Clin Dis 1965;18:797-814. G&m TC, White KL, Kahter LM The prevalence of congestiie heart failure in two communities. J Chronic Dis 1966;19:141-152. National Drug and Therapeutic Index Review. Ambler, Pennsylvania: IMS America, 1983. Jofmson RA, Palactos I. Dilated cardicmycpathies of the adult. N Eng! J Med

1982;307:1051-1058. 6. Keshan Disease Research Group of the Chinese Academy of Medical Sciences, Beijing. Epidemiologic studies in the etiologic relationship of selenium and Keshan Disease. Chin Med J 1979;92:477-482. 9. Edmunds AW. Idiopathic cardiomyopathy in Botswana. J Trop Med Hyg 1979;82:14-17. 10. Stollerman GH. Rheumatic Fever and Streptococcal Infection. New York: Grune and Stratton, 1975. 11. Gordis L Effect of comprehensive care programs in preventing rheumatic fever. N Engl J Med 1973;289:331-335. 12. McKee PA, Caste11 WP, McNamara PM. Kannel WB. The natural history of congestive heart failure: the Framingham study. New Engl J Med 1971:285:1441-1446. 13. Torp A. Incidence of congestive cardiomyopathy. Postgrad Med J 1978; 54:435-437. . 14. Boucher CA, Fallon JT, Johnson RA, Yurchak PM. Cardiomyopathic syndrome caused by coronary artery disease. III: prospective clinicopathological study of Its prevalence among patients wtth clinically unexplained chronic heart failure. Br Heart J 1979;41:613-620. of heart failue. Curr Prob Cardiol 15. Gazes PC, Assay ME. The management 1984:8:1-10. 16. Ross j. Effects of afterload or impedence on the heart: afterload reduction in the treatment of cardiac failure. Cardiovasc Med 1977;2: 1115. 17. Cohn JN. Symppsium on vasodilators. F’rog Cardiovasc Dis 1981-1982; 24:89.275.353.419. 18. Lee DC-S,‘Johnson RA, Bingham JB, Leahy Y, Dinsmore RE, Goroll AH, NewaY JB, Strauss HW, Habsr E. Heart failve in outpatients. A randomized trial of digoxin versus placebo. N Engl J Med 1982;306:699-705. lg. Wlthsrii W. An account of the foxglove and some of its medical uses: with prx;ctcaI remarks on biopsy and other diseases. Birmingham: M. Swinney, 20.

Maskin CS, Fotman R, Klein NA, Sonnsnblkk EA, LeJemtel TH. Long-term amrinone therapy in patients with severe heart failure: drug-dependent hemodynamic benefiis despite progression of the disease. Am J M&t 1982;72:113-118. 21. Starral LA. LeJemtal TH. Strom J. Maskin C. Forman R. Frlstvnan W. we&J, klbner H, So&nblick EH. Improv&ent in exercise capacity despite cardiac detericfaticn: non-invasive assaqrxmt of to term ths&y with amrinone in severe heart failure. Am Heart J 1983;iO 7 :1042-1047. 22. Rader B, Smith WW, Berger AR, Eidina LW. Comparison of the hemodynamic effects of mercurial diwetics and digitalis in congesttve heart failure. Circulation 1964;29:328-345. of increased venous tone in chronic ccqestive heart 23. Burch GE. Evidence failure. Arch Intern Med 1956:98:750-766. 24. Johnson JB, Gross JF. Hale B. The effect of sublingual nitroglycerine in pulmcnary artery presswe in patients with failure of the teft vent&% N Engl JMed 1957:257:1114-1117. 25. Packer M. Vasoditator and inotrcpic tharapy for severe chronic heart failue: passions and skepticism. JACC 1983;2:841-852. 26. Franc&a JA, Nordstrom LA, Cohn JN. Nitrate therapy for congestive heart failure. JAMA 1978;240:443-446. 27. Leier CV, Huss P, Mogorten RD, Unvertedh DV. Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure. Circulation 193;67:817-822. 26. Kramer BL, Massia BM, Topic N. Controlled trial of captopril in chronic heart failure: rest and exercise hemodynamic study. Circulation 1983;67: 807-816. 29. Captopril Multicenter Research Goup. A phcebocontrolled triil of captcpril in refractory chronic congestive heart failure. JACC 1983;2:755-763.