Increasing attention has been given to preserved ejection fraction heart failure (HFPEF) in the general population, but little is known about this clinical entity in patients with end-stage renal disease. A recent study published in the American Journal of Kidney Diseases helps shed some light on the prevalence, clinical profiles, and long-term outcomes of peritoneal dialysis (PD) patients with HFPEF. Dr. Angela Wang (AW), lead author of the article, discusses this topic with Dr. Abdo Asmar (eAJKD), eAJKD Contributor.
eAJKD: Why are you interested in this subject, and why is it important?
AW: Heart failure is a very frequent and important complication in patients with chronic kidney disease, especially among those on dialysis. Previous studies by Harnett et al and ours demonstrated the importance of heart failure in predicting adverse clinical outcomes in long-term dialysis patients. Studies in the general population have investigated differences between heart failure with preserved (or so-called diastolic heart failure) or reduced ejection fraction. However, there are so far no studies differentiating heart failure with preserved or reduced ejection fraction in dialysis patients. Whether the pathogenesis, treatment strategies, and clinical outcomes may differ in these two types of heart failure in dialysis patients are currently not known. This forms an important rationale and background for conducting the current observational study.
eAJKD: Was there anything that surprised you about the results of your study?
AW: There are several major and important findings from our study which have not been reported previously. First, we observed a very high prevalence of HFPEF (55%) in PD patients. Second, over a prospective follow-up period of 4 years, we showed that PD patients having HFPEF were associated with an increased risk of mortality and adverse cardiovascular outcomes including cardiovascular death, fatal or non-fatal cardiovascular events, and heart failure compared to those patients without heart failure. However, the risk for all-cause mortality, cardiovascular death, fatal or non-fatal cardiovascular events, and heart failure was lower when compared to patients having heart failure with reduced ejection fraction (HFREF). Third, there are clearly important differences in the baseline clinical characteristics of patients with HFPEF and HFREF that may explain why subsequent mortality and clinical outcomes of HFPEF patients were different from the HFREF patients. The clinical and biochemical profiles as well as the prevalence of diabetes and coronary artery disease of patients with HFPEF were intermediate between those with HFREF and no heart failure. Furthermore, compared to patients with HFREF, HFPEF patients had less severe cardiac hypertrophy and dilatation as well as less severe systolic and diastolic dysfunction and lower cardiac troponin T and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels. However, the cardiac structure and function of HFPEF patients were worse when compared to patients with no heart failure.
eAJKD: Diuretics were not part of the medical regimen in the patients you studied, and only less than third of the patients with HFPEF were on ACEi or ARB. Do you think that this had any effect on the outcomes?
AW: We currently do not know if the use of diuretics or ACEi or ARB treatment may improve clinical outcomes of dialysis patients with heart failure and preserved ejection fraction. A prospective randomized controlled trial will be required to answer this important question. Nevertheless, as shown in Table 1, the HFREF group had the highest use of ACEi or ARB, but only 46% of the HFREF group of patients and 28% of the HFPEF patients received treatment with ACEi or ARB, suggesting that this class of agent is somewhat underused even among dialysis patients with heart failure.
In addition, as you may appreciate when reading Table 2 in our article, the percentage of patients with preserved residual kidney function as well as the actual residual kidney function showed a decline across the three groups of patients with no heart failure, HFPEF, and HFREF, with a trend towards significance. This data is well worth noting, and suggests that the loss of residual kidney function may be related to heart failure in PD patients. However, we cautioned that the association observed is purely cross-sectional and cannot infer causal relationship.
eAJKD: Your study showed that patients with HFPEF had better outcomes compared to HFREF. Why do you think this is different from what is seen in the general population where the mortality is similar?
AW: This question remains quite controversial in the general population as well. While some earlier studies demonstrated similar outcomes for patients with HFPEF and HFREF, there is recent suggestion from general population study that the clinical outcomes of patients with HFPEF were better than those with HFREF. In dialysis patients, as one may appreciate, the baseline clinical and biochemical characteristics of HFPEF patients were intermediate between those with HFREF and those with no heart failure. Furthermore, the cardiac biomarkers such as cardiac troponin T (reflecting myocardial injury) and NT-pro-BNP (reflecting an increased LV wall stress) were also elevated in patients with HFPEF compared to those with no heart failure, though not as high as in patients with HFREF. Likewise, the degree of cardiac hypertrophy, dilatation, and systolic and diastolic dysfunction was also less severe in HFPEF patients when compared to HFREF patients. This may explain why mortality as well as other clinical outcomes of HFPEF patients was better than the HFREF patients.
eAJKD: How do you think the clinical differentiation of HF (HFPEF vs. HFREF) in PD patients might affect therapeutic strategies and future studies?
AW: It is currently not known whether heart failure with preserved and reduced ejection fraction in dialysis patients may represent distinct heart failure phenotypes, and whether their pathogenesis and treatment strategies may differ. This will be the focus of future studies. In the general population, HFPEF appears to have similar, though not as severe, pathophysiologic characteristics compared to those with HFREF. These histopathologic differences may be of relevance to dialysis patients and warrant further investigation. In dialysis patients, it appears that the clinical, biochemical, and echocardiographic profiles are the worst in HFREF patients, followed by HFPEF patients. Given the differences in the clinical outcomes and various characteristics of dialysis patients with HFREF and HFPEF, it raises an important clinical question whether one needs to differentiate therapeutic strategies for these 2 groups of patients. It is currently not known whether therapeutic strategies for heart failure such as beta-blockers and renin-angiotensin-aldosterone blockers may be equally effective and useful in these two types of heart failure. Further studies are required to elucidate this key question.