Prognostic implications of plasma volume status estimates in heart failure with preserved ejection fraction: insights from TOPCAT

Abstract

Aims Plasma volume expansion is clinically and prognostically relevant in individuals with heart failure. Prior cohorts either excluded or had limited representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between calculated plasma volume status (PVS) and outcomes in HFpEF. Methods and results We included enrollees from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) with available haematocrit and weight data (n = 3414). Plasma volume was derived from the Hakim formula and compared to estimates of ideal plasma volume to generate a relative PVS. Multivariable Cox proportional hazards models tested the association of PVS with clinical outcomes. The median PVS was –11.9% (25th–75th percentile: –17.2% to –6.4%) and the majority (91.1%) had PVS consistent with relative volume contraction (PVS ≤ 0%) as opposed to volume expansion (8.9%, PVS > 0%). After multivariable adjustment, each 5% increment in PVS was associated with a ∼11%, 14%, and 12% higher risk for the primary composite endpoint, all‐cause death, and heart failure hospitalization, respectively (P < 0.002 for all), but not cardiovascular death (P = 0.051). After additional adjustment for natriuretic peptides, PVS only remained associated with heart failure hospitalization (HR 1.10, 95% confidence interval 1.001–1.21, P = 0.047). There were no significant interactions between spironolactone use and the PVS–risk relationship for any endpoint (P > 0.1 for all). Conclusion Higher calculated estimates of PVS were independently associated with a higher risk of long‐term clinical outcomes in HFpEF, and particularly, heart failure hospitalization.

CRP Induces NETosis in Heart Failure Patients with or without Diabetes

“…The characterization and recruitment of HF patients was in concordance with the guidelines set in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist clinical trial (24), which was prior to the setting of the new European Society for Cardiology guidelines (1). Therefore, HF patients recruited from the MHI Heart Failure Clinic were classified as HFrEF if their LVEF was #40% or HFpEF if their LVEF was $45% (24)(25)(26), as documented by contrast ventriculography, magnetic resonance imaging, radionuclide ventriculography, or quantitative echocardiography within the previous 12 mo if no cardiac event occurred since the measurement of their LVEF (24). In addition to the previous inclusion criteria for the HF patients, the HF plus T2DM patients had also an HbA1c ,10% and were controlled by any available hypoglycemic medications and, as per guidelines, were treated with preventive hypertension medication.…”

Impact of calculated plasma volume status on all-cause and cardiovascular mortality: 4-year nationwide community-based prospective cohort study

“…Peter et al reported that PVS of -6.5% optimally predicted absence of adverse outcomes, and the rate of cardiac events were increased with advancing plasma expansion in patients with heart failure with reduced ejection fraction and those with mid-range ejection fraction [18]. The TOPCAT study demonstrated that increment in PVS is associated with a higher risk of all-cause death and heart failure hospitalization in patients with heart failure with preserved ejection fraction [13]. Taking these results into consideration, PVS could be a useful predictor of poor clinical outcome in patients with heart failure independently of ejection fraction.…”

“…Recently, plasma volume status (PVS), an index of the degree to which patients have deviated from their ideal plasma volume, is gaining attention in patients with heart failure. PVS is associated with cardiac events and mortality in patients with heart failure [ 13 – 15 ]. American College of Cardiology/American Herat Association guidelines have recommended volume status be assessed [ 16 ].…”

Spironolactone: diuretic or disease‐modifying drug in heart failure with preserved ejection fraction?

“…between spironolactone use and calculated plasma volume for any endpoint. 10,11 In this issue of the journal, Kalogeropoulos et al 12 provide important further insights into the effects of spironolactone on subsequent diuretic use, electrolytes and serum creatinine, as well as their relationship with the risk for HF readmission. In brief, spironolactone had a marginal (<1%) and short-term (first 8 months) effect on weight loss in the American population of the TOPCAT trial, with superimposed curves after 1 year.…”