Dr Myerson is Director of Preventive Cardiology, St. Luke’s-Roosevelt Hospital, Columbia University College of Physicians and Surgeons, New York, NY.
Surprising New Data Show Serious Prognosis, Patient Characteristics
For many years, a diagnosis of heart failure (HF) indicated that a patient had left ventricular (LV) systolic dysfunction and a reduced ejection fraction. There may have even been an imaging study to document this, but a clinical diagnosis was enough. After many years of no change, new research is changing the way we look at HF, with data suggesting that HF with normal ejection fraction, also referred to as diastolic HF, is increasingly common and is not as benign as previously thought, and patient characteristics have now been identified.
Two things gradually changed over the years with regard to HF:
First, the increased use and greater sophistication of imaging, in particular echocardiography, has allowed physicians to more precisely make cardiac diagnoses.
Second, patients were presenting to their doctors complaining of dyspnea, but echocardiographic studies were showing a normal ejection fraction. However, the echo did show something else—abnormalities in the relaxation of the left ventricle, now known as diastolic dysfunction.
Initially, it was thought that patients with HF associated with diastolic dysfunction had a more benign course than HF caused by systolic dysfunction. Relatively little was known about who had diastolic dysfunction and what would be the clinical course that those patients could expect.
New England Journal of Medicine
In July 2006, 2 articles published in the 1,2 shed new light on HF that is associated with diastolic dysfunction. The authors provided epidemiologic evidence showing that the survival of patients with diastolic dysfunction was similar to, or only slightly better than, that for patients with HF and a reduced ejection fraction.
HF: Many Names for Many Forms
Any research, or even discussion, about HF should first address the problems with terminology, but this was not often done in the past when discussing HF. Terms used to describe and define HF have not been standardized, often leading to confusion:
• “Congestive HF” is a clinical term that represents a constellation of signs and symptoms, including pulmonary congestion and dyspnea.
• “Systolic HF” is the term used to describe impairment of the left ventricle when it contracts during systole. Some patients may have systolic HF without congestion, and therefore they do not have clinically manifested HF.
• The term “diastolic HF” refers to abnormalities of the left ventricle in the relaxation phase, or diastole. Once again, patients may have this abnormality yet not have any symptoms.
Many clinicians and researchers have been using the term “HF with a preserved ejection fraction” when referring to diastolic HF. Thus, clarification was clearly needed.
New Data Shed Light on Diastolic HF
The 2 new studies on HF are among the first to provide data describing what type of patients have diastolic HF, what conditions are associated with it, and what their prognosis is.
Owan and colleagues studied white inpatients at the Mayo Clinic hospitals in Olmsted County, Minnesota, from 1987 to 2001. Patients were included if they had a discharge code of 428 (congestive HF). Echocardiographic assessment of ejection fraction was available for 4596 patients (76%), who were then classified as having either preserved or reduced ejection fraction.
The study found that:
• Patients with a preserved ejection fraction (authors’ term for diastolic HF) were more likely to be female and older compared with those with a reduced ejection fraction (systolic HF).
• The coexistence of hypertension and atrial fibrillation was greater in those with a preserved ejection fraction, but the presence of coronary artery and valve disease was lower.
• The prevalence of HF and a preserved ejection fraction increased over time, even with adjustment for age.
• The survival rate was greater in those with a preserved ejection fraction compared with a reduced ejection fraction, although the difference was small. Over the time of the study, the survival rate for those with a reduced ejection fraction increased, but the rate did not change for those with a preserved ejection fraction.
In the second study, Bhatia and colleagues from Toronto evaluated hospitalized patients in Canada (with a discharge code of 428) who met the Framingham Study criteria for HF and who had undergone echocardiographic assessment of LV function.
Patients were divided into 2 groups: those with an ejection fraction <40% (n = 1570) and those with an ejection fraction >50% (n = 880). Patients with an ejection fraction between 40% and 50% were excluded.
Like the Mayo study, the Canadian team found that those with a preserved ejection fraction were more likely to be older and female, and had higher rates of hypertension and atrial fibrillation but lower rates of coronary artery disease.
At 30 days and at 1 year, mortality rates were not significantly different between the 2 groups, suggesting that the prognosis for diastolic HF was not different from that for systolic HF.
A Sea Change
The findings from these 2 studies that the prognosis for patients with diastolic HF did not differ greatly when compared with patients with systolic HF came as somewhat of a surprise. The few existing studies had suggested otherwise.
A small study published in 20033 showed that there was clinically important morbidity and mortality associated with diastolic HF, but the findings did not support a higher mortality rate compared with patients with systolic HF.
This study looked at hospital admissions in 413 white patients aged ≥50 years with HF. Those with a preserved ejection fraction tended to be older and female. At 6 months, 13% with a preserved ejection fraction died compared with 21% with a reduced ejection fraction (a significant difference). After adjusting for covariates, preserved ejection fraction was associated with a lower risk of death, but there were no differences in the rate of functional decline.
The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) study4 was designed to compare treatment options for outpatients with New York Heart Association class II to IV disease. Patients with higher ejection fractions and symptoms of HF were older and more likely to be female.
The authors found that the risk of death declined with increasing ejection fraction up to 45%; the risk of death remained relatively stable with ejection fraction >45%. The authors concluded that an ejection fraction above 45% does not add to cardiovascular risk in patients with HF. Of note, the patients in the CHARM study were younger and more heterogeneous than those in the new studies.1,2
Important Clinical Implications
Despite the difficulties in studying HF, these 2 recent studies highlight several important points:
• HF of any type is increasing in prevalence, and HF is a significant cause of morbidity and mortality.
• HF with preserved ejection fraction, or diastolic dysfunction, once thought to be relatively benign, clearly needs to be reckoned with.
• Older persons, and of these especially women, are disproportionately affected.
• Hypertension was found to be associated with diastolic HF. Underdiagnosis and undertreatment of high blood pressure is still a problem, although progress is being made in this area.
• Now that we are realizing the impact of diastolic HF, we need to know how to help prevent it from occurring and how to treat it once it does occur.
Limitations in the Literature
Studies of HF, in particular those focusing on epidemiology, are challenging for many reasons. One in particular is that the definitions used for HF vary from study to study, especially for diastolic HF.
Many studies focus on inpatients as opposed to outpatients, since it is easier to gather information about patients in the hospital setting. However, HF is both an inpatient and outpatient disease, and many individuals present first as outpatients. Others may not present to a hospital for many years, if at all.
The initial HF presentation may be missed, making determinations of incidence and prevalence difficult. In addition, many studies have been limited to white populations, making it hard to generalize or extrapolate their findings to other groups. Finally, it may be hard to account for confounding factors. For example, the increasing prevalence of diastolic HF may be due, in part, to the increasing awareness and ability of physicians to make this diagnosis rather than an increase in incidence.
The new studies should serve as the basis for expanded research that should include diverse ethnic and racial groups. Obtaining outpatient information is challenging but is much needed.
N Engl J Med.
1. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. 2006; 355:251-259.
N Engl J Med.
2. Bhatia RS, Tu JV, Lee DS, et al. Outcome of heart failure with preserved fraction in a population- based study. 2006; 355:260-269.
J Am Coll Cardiol.
3. Smith GL, Masoudi FA, Vaccarino V, et al. Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline. 2003; 41:1510-1518.
4. Solomon SD, Anavekar N, Skali H, et al. Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients. 2005;112:3738- 3744.