Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction in Women

Heart failure remains the No. 1 discharge diagnosis for Medicare recipients in US hospitals. More than 40% of patients admitted for acutely decompensated heart failure have preserved systolic function (ie, heart failure with preserved ejection fraction [HFPEF]) and DD. As therapies for HF with reduced EF improve outcomes, proportionally more patients will present with HFPEF, many of whom will be older women and will have hypertension and/or diabetes mellitus. The in-hospital mortality rate may be low but after discharge it can be as high as that of patients with impaired systolic function. Indeed, as well stated by Yip and colleagues, diastolic dysfunction is only one of many pathophysiologic derangements in DD and incorrectly may lead the physician to target therapy only to diastole. As such, HFPEF mechanisms are complex and include metabolic and mechanical abnormalities of systole and diastole. The added effects of hypertension and diabetes mellitus, among comorbidities, cannot be ignored. Yet, the diagnosis of HFPEF usually is made based on symptoms while physicians look to the echocardiographic test results to “seal” the diagnosis of DD. After several failed trials, as investigators continue to struggle to find a specific therapy for HFPEF, the question arises of whether we truly know the pathophysiologic character of this syndrome. Does DD exist that does not progress to HF? If the physician identifies DD in a patient with mild or no symptoms, will that patient progress to frank heart failure and have a higher mortality risk? Are the outcomes for those patients linked to the DD level of severity, or should we consider other factors? These important questions need to be answered for physicians to advise and treat patients with DD. The continuum of DD from mild and asymptomatic to severe and symptomatic is being constructed by pieces, as is a puzzle. Investigators have studied patients with DD from the epidemiologic perspective and based their observations on patients enrolled in a variety of clinical trials. Data have been derived from patients enrolled due to their age group or as part of large cohort studies. The prevalence of DD and HF has varied significantly among studies depending on the population. In a community setting, the prevalence of DD has been as high as 28%. Echocardiographic studies of severe DD have followed up patients through progression to HF. Similar to the registries, the patients tended to be women and to have multiple comorbidities. Nevertheless, most studies agree that DD is more common than expected even in individuals without symptoms and that, depending on other risk factors such as hypertension, the incidence of HF and symptoms occurs at a rate of 31% during 2 years. Still missing are reasons why some processes lead to frank HFPEF. In this issue of the Archives, Halley and colleagues present another portion of the spectrum of DD with echocardiographic data that span 9 years. Consistent with clinical practice, 19.7% of echocardiographic test results were obtained for symptom evaluation or assessment of ventricular function. In agreement with results from a previous study, the prevalence of DD is high; in fact, it is higher than that reported in the community setting. However, compared with Correa de Sa et al, who examined the Mayo Clinic database to determine the progression from DD to HF, Halley et al have gone one step further by reporting the mortality outcomes of patients during a follow-up period of more than 6 years by levels of DD from mild to moderate and severe. The database is powerful, with extensive clinical records in addition to the echocardiographic findings and an adequate representation of women. The authors wisely included patients who already had a diagnosis of HF at presentation, although the prevalence was low. Comorbidities were more common in those with moderate to severe DD. Using elegant propensity matching and controlling for comorbidities, moderate and severe DD were shown to be independent predictors of mortality. This finding is novel and important for physicians. However, an interesting contrast exists compared with other reports. The women in the study by Halley et al are younger than those in other registries and clinical trials of HFPEF, despite a large sample. Given the low prevalence of HF in the database, is the progression of DD to frank HFPEF in women different than that in men? The Cardiovascular Health Study examined the progression to HF and found that individuals with comorbidities (eg, hypertension and diabetes) were more likely to develop incident HF. Perhaps the symptoms in women do not manifest at a younger age (ie, more chronically) but acutely, in the form of decompensated HF. In patients with acute HF due to HFPEF, 45% present de novo. Comorbidities may be the salient presentation for older women, thus not triggering the need for echocardiographic testing. Per se, these patients would not be included in this database. Also, in the report by Halley et al, the mean age was 58, (ie, younger than the mean age of presentation of HFPEF in men and, certainly, in women). Nevertheless, more men than women were among the 73 of 127 patients with severe DD who were older than 65 years.