The Optimal Plasma Volume Status in Heart Failure in Relation to Clinical Outcome

Background: Progressive plasma volume (PV) expansion is a hallmark of chronic heart failure (HF), ultimately contributing to decompensated heart failure. Monitoring PV might offer prognostic information and might be a target for tailored therapy. Methods and Results: The correlation between technetium-99 (Tc-99)-labeled red blood cell measured PV and calculated PV was first determined in a validation cohort. The relationship between PV status (PVS; a marker how much actual PV deviated from the ideal PV) and outcome was analyzed with the use of Cox proportional modeling in a prospective chronic HF (CHF) population (the outcome cohort). Thirtyone HF patients were included in the validation cohort. Calculated PV correlated well with Tc-99-measured PV (r = 0.714; P = .001). A total of 1173 patients (HF with reduced ejection fraction [HFrEF]: n = 872; HF with mid-range EF [HFmrEF]: n = 229; HF with preserved EF [HFpEF]: n = 72) were prospectively included in the outcome cohort. The mean PVS in the outcome cohort was -6.7% +/- 10%, indicating slight PV contraction. Higher PVS was independently associated with increased risk for HF hospitalization and all-cause mortality (hazard ratio 1.016; 95% confidence interval 1.006-1.027 per 1% increase in PVS; P = .002). Receiver operating characteristic curve analysis indicated that a PVS of 6.5% optimally predicted absence of adverse outcome. Hazard ratio analysis indicated that CHF patients were less equipped in tolerating PV expansion in comparison to PV contraction. The use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and mineralocorticoid receptor antagonists were independently associated with a higher odds of having an optimal PVS in HFrEF and HFmrEF (all P < .05), but not in HFpEF. Conclusions: Calculated PV correlates well with measured PV in HF patients. An increase in PV is independently associated with a higher risk of adverse outcome, and a slight contraction of the predicted PV seems to be related to less adverse events. Higher dosages of renin-angiotensin-aldosterone blockers are associated with higher odds of having an optimal PV status.