Natural history of congestive heart failure

Apr 26, 2000

Heart failure (HF) is a common clinical syndrome. In the United States, for example, two to four million patients carry this diagnosis, there are more than 400,000 new cases per year, and, in 1989, HF was the primary diagnosis in 643,000 hospital discharge records [1,2]. Approximately 1.5 to 2 percent of the population has HF and the prevalence increases to 6 to 10 percent among patients over 65 years of age [1,3]. The number of patient-days of hospitalization has nearly doubled since 1973, resulting in an enormous economic impact [4,5]. Furthermore, the prevalence of HF is expected to increase in the future due to aging of the United States population.

SURVIVAL IN SYMPTOMATIC CHF — Morbidity and mortality after the onset of symptomatic CHF is extremely high. In a 38 year follow-up of patients in the Framingham study, the presence of CHF significantly increases overall and sudden cardiac death (SCD) mortality [6]. The incidence of SCD in those with CHF, compared to those without CHF, was increased five-fold in either sex, although the absolute risk in women was only one-third that of men (show figure 1). The SCD death potential in men and women with CHF was as great as that noted in patients with overt coronary heart disease (13.7 and 3.8 versus 12.9 and 2.4 per 1000 patients, respectively). An increased risk in men compared to women has also been noted in other studies of patients with advanced CHF, primarily those with a nonischemic etiology [7].

The following statistics refer to patients with systolic heart failure, since the natural history of diastolic dysfunction is less well defined. (See "Systolic versus diastolic dysfunction in congestive heart failure").

Among patients hospitalized for heart failure, in-hospital mortality and length of hospital stay have decreased, despite an increase in the severity of heart failure. As an example, one study of 6676 patients hospitalized for heart failure found that, over a 10 year period (1986 to 1996), there was a reduction of in-hospital mortality from 8.4 to 6 percent and length of hospital stay from 7.7 to 5.6 days [8]. However, adjusted costs were unchanged, possibly because of an increased use of cardiac procedures.

Although in-hospital mortality has decreased, long-term outcome remains poor. Initial studies noted a mortality rate of 50 percent within two years and up to 60 to 70 percent within three years [9]; the median survival was 1.7 years in men and 3.2 years in women. A number of controlled trials have shown that survival can be prolonged in CHF due to systolic dysfunction by the administration of angiotensin converting enzyme (ACE) inhibitors (show figure 2 and show figure 3) [10,11], spironolactone (show figure 4) [12], and beta blockers (show figure 5) [3]. (See "Pharmacologic therapy of symptomatic congestive heart failure", section on ACE inhibitors).

Despite the advances in therapy, longitudinal data from the Framingham study and the Mayo Clinic suggest that there has not been much improvement in the one-year survival of patients with newly diagnosed symptomatic CHF, which remains between 60 and 70 percent [13,14]. At least a partial explanation for this finding is that, during the period covered by these studies, only a minority of patients with CHF were appropriately treated [15]. As late as 1992, for example, less than 25 percent of patients with CHF were receiving ACE inhibitors [14]. Even among treated patients, the doses used were lower than those in the clinical trials. However, mortality is still high when ACE inhibitors are prescribed. As an example, in one study of 499 patients with class III or IV CHF, 75 percent were receiving an ACE inhibitor and 50 percent were treated with digoxin; the one-year mortality was 35.4 percent and the rate of death or hospital readmission (2.05 times and 27.6 days per year) was 81 percent [16].

It is also important to appreciate that the survival benefit associated with ACE inhibitors and hydralazine plus nitrates, although statistically significant, is relatively modest in absolute terms. Most studies have reported a 15 to 20 percent reduction in overall mortality. In the SOLVD trial of New York Heart Association Class II and III heart failure, for example, enalapril lowered the four-year mortality rate from 42 to 36 percent; this represents an absolute improvement of six percent (show figure 3) [11]. Averaging the benefit from these studies through the entire treated population translates into a mean increase in survival of less than six months [14]. Thus, the benefit is apparent only in large populations.

Outcome based on etiology of cardiomyopathy — The etiology of heart failure may be predictive of long term outcome. (See "Definition and classification of the cardiomyopathies"). This was addressed by one study of 1230 patients with a cardiomyopathy which analyzed the outcome based on the etiology of the cardiomyopathy; after a mean follow-up of 4.4 years, 34 percent of patients died and 4.6 percent underwent cardiac transplantation [17]. Compared to those with a idiopathic cardiomyopathy, which served as the reference group, patients with peripartum cardiomyopathy had a better outcome (hazard ratio 0.31); in contrast the outcome was worse when the etiology was infiltrative myocardial disease, particularly amyloidosis or hemochromatosis (hazard ratio 7.41 and 8.88, respectively); HIV infection (hazard ratio 5.86); doxorubicin therapy (hazard ratio 3.46); ischemic heart disease (hazard ratio 1.52); or connective tissue disease (hazard ratio 1.75). The outcome was the same when the etiology was hypertension, myocarditis, sarcoidosis, substance abuse, or other causes.

Outcome based on specialty care — It is more costly to provide specialized care to a patient with heart failure by a cardiologist compared to a generalist because of the use of more diagnostic techniques and longer hospitalizations. However, one retrospective chart review of 298 patients found that the risk of rehospitalization within six months for heart failure was 1.7-fold greater when care was provided by a generalist, though all-cause and cardiac mortalities were the same [18]. This issue was further examined by the SUPPORT study which prospectively followed 1298 patients hospitalized for heart failure [19]. After adjustment for sociodemographic characteristics and illness severity, the cost of care was 43 percent higher when provided by a cardiologist compared to a generalist, primarily because cardiologists were more likely to perform invasive procedures. At six months, there was no difference in mortality among patients cared for by a cardiologist or generalist (27 percent), but there was a trend towards improved survival at one year among patients of cardiologists.

Rehospitalization — The readmission rate for decompensated CHF is increasing; among elderly patients, CHF exacerbation is one of the most common reasons for rehospitalization, ranging from 27 to 47 percent within three to six months of initial hospitalization [20]. In one series, the most common reason for readmission, identified in 41 percent of patients, was lack of adherence to the medical program (drug or diet); another 12 percent received inadequate preadmission treatment [21]. Thus, more than one-half of readmissions were regarded as preventable.

A nurse directed, multidisciplinary intervention for management of these patients can significantly reduce the the number of hospitalizations and improve quality of life [22,23]. In a randomized trial, patients receiving intensive intervention had a lower incidence of readmissions (39 versus 54 percent) and a shorter duration of hospitalization (7.8 versus 14.3 days). The annual reduction in health care cost was $1300 per patient.

Another study of 214 patients with class III or IV CHF accepted for heart transplantation found that comprehensive CHF management which included intensive patient education, resulted in an improved functional status during the six months after referral to a heart failure program [24]. When compared to the 6 month period before referral there was an 85 percent decrease in hospital readmission rate with an estimated savings of $9800 per patient (in 1997 dollars). No significant change in mortality was detectable (show figure 6).

Seasonal variation — Several studies have found a seasonal pattern of deaths from myocardial infarction and sudden death, with more fatal events occurring in the winter than the summer. (See "The role of psychosocial factors in acute myocardial infarction" and see "The role of psychosocial factors in sudden cardiac death"). A similar seasonal variation has been seen in chronic CHF. In a large study from France, deaths from CHF peaked during the winter months of December and January [25]. The distribution of monthly deaths differed by up to 35 percent when January was compared to August, which is when deaths were the lowest [25]. Hospitalizations for CHF followed the same seasonal pattern, with a winter-spring predominance (show figure 7).

CHF due to diastolic dysfunction — The prognosis of patients with CHF due to diastolic dysfunction is less well defined even though they constitute up to 50 percent of patients with symptomatic CHF. The Framingham Heart Study found that among 73 patients with CHF, 51 percent had normal left ventricular systolic function (diastolic dysfunction), 65 percent of whom were female [26]. After a median follow-up of 6.2 years, patients with CHF due to diastolic dysfunction had a higher mortality than matched controls (8.7 versus 3 percent). In contrast, the mortality was higher in patients with CHF due to systolic dysfunction (18.9 versus 4.1 percent for matched controls) (show figure 8). (See "Diagnosis, treatment, and prognosis of diastolic dysfunction").

CAUSES OF DEATH IN CHF — The two main causes of death in patients with CHF are "sudden" or arrhythmic death (defined as death within one hour of the onset of cardiovascular collapse in a previously stable patient) and progressive pump failure (defined as cardiac death with preceding symptomatic or hemodynamic deterioration) [10,11]. Published series suggest a relatively consistent pattern that from 30 to 50 percent of all cardiac deaths are categorized as sudden deaths, with or without preceding symptoms [11,27,28]. However, it is often difficult to distinguish between those dying suddenly and unexpectedly from those experiencing terminal arrhythmias in the setting of progressive hemodynamic deterioration. The benefit of ACE inhibitors, on the other hand, is primarily derived from prevention of progression of myocardial dysfunction, rather than prevention of sudden death [10,11,27,28].

SURVIVAL IN ASYMPTOMATIC CHF — Effective prevention of CHF requires the early detection and treatment of predisposing conditions and risk factors [29]. The prognosis in asymptomatic LV dysfunction is much better than that in symptomatic patients. One- and four-year survival rates are approximately 95 and 81 percent, respectively [27]. Prevention or delay of the onset of symptomatic CHF may have a dramatic impact on the natural history of this syndrome. In particular, initiation of therapy with ACE inhibitors prevents or delays the onset of symptomatic heart failure in patients with asymptomatic, or minimally symptomatic left ventricular systolic dysfunction (show figure 9) [27,28,30]. The substantial decrease in mortality in these trials suggests that the optimal time for intervention with ACE inhibitors is at the onset of left ventricular dysfunction, even in the absence of overt clinical symptoms of heart failure. (See "Pharmacologic therapy of symptomatic congestive heart failure").