Discordance between estimated and measured changes in plasma volume among patients with acute heart failure.

AIMS: In acute heart failure (AHF), changes of venous haemoglobin (Hb) concentrations, haematocrit (Hct), and estimated plasma volume (ePV) have been proposed as surrogates of decongestion. These estimates are based on the theoretical assumptions that changes of Hb concentrations and Hct are driven by the intravascular volume status and that the intravascular Hb pool remains stable. The objective of this study was to assess the relationship of changes of measured plasma volume (mPV) with changes of Hb, Hct, and ePV in AHF. METHODS AND RESULTS: We studied 36 AHF patients, who received two sequential assessments of mPV, measured red cell volume (mRCV) and measured total blood volume (mTBV) (48 h apart), during the course of diuretic therapy using a novel visible fluorescent injectate (VFI) technique based on the indicator dilution principle. Changes of ePV were calculated based on the Kaplan-Hakim or Strauss formula. AHF patients receiving diuretics (median intravenous furosemide equivalent 160 mg/48 h) displayed a wide range of changes of mPV (-25.4% to +37.0%). Changes in mPV were not significantly correlated with changes of Hb concentration [Pearson's r (r) = -0.241, P = 0.157], Hct (r = -0.307, P = 0.069), ePVKaplan-Hakim (r = 0.228, P = 0.182), or ePVStrauss (r = 0.237, P = 0.163). In contrast to theoretical assumptions, changes of mTBV were poorly correlated with changes of Hb concentrations and some patients displayed unanticipated variability of mRCV, suggesting an unstable intravascular red cell pool. CONCLUSIONS: Changes of Hb or Hct were not reflective of directly measured changes of intravascular volume status in AHF patients. Basing clinical assessment of decongestion on changes of Hb or Hct may misguide clinical decision-making on an individual patient level.

Serum creatinine and cystatin C-based estimates of glomerular filtration rate are misleading in acute heart failure.

AIMS: We aimed to test whether the endogenous filtration markers serum creatinine or cystatin C and equation-based estimates of glomerular filtration rate (GFR) based on these markers appropriately reflect changes of measured GFR in patients with acute heart failure. METHODS: In this prospective cohort study of 50 hospitalized acute heart failure patients undergoing decongestive therapy, we applied an intravenous visible fluorescent injectate (VFI), consisting of a low molecular weight component to measure GFR and a high molecular weight component to correct for measured plasma volume. Thirty-eight patients had two sequential GFR measurements 48 h apart. The co-primary endpoints of the study were safety of VFI and plasma stability of the high molecular weight component. A key secondary endpoint was to compare changes in measured GFR (mGFR) to changes of serum creatinine, cystatin C and estimated GFR. RESULTS: VFI-based GFR measurements were safe and consistent with plasma stability of the high molecular weight component and glomerular filtration of the low molecular weight component. Filtration marker-based point estimates of GFR, when compared with mGFR, provided only moderate correlation (Pearson's r, range 0.80-0.88, depending on equation used), precision (r2 , range 0.65-0.78) and accuracy (56%-74% of estimates scored within 30% of mGFR). Correlations of 48-h changes GFR estimates and changes of mGFR were significant (P < 0.05) but weak (Pearson's r, range 0.35-0.39). Observed decreases of eGFR by more than 15% had a low sensitivity (range 38%-46%, depending on equation used) in detecting true worsening mGFR, defined by a >15% decrease in mGFR. CONCLUSIONS: In patients hospitalized for acute heart failure, serum creatinine- and cystatin C-based predictions performed poorly in detecting actual changes of GFR. These data challenge current clinical strategies to evaluate dynamics of kidney function in acute heart failure.

Effects of combination of AT1-antagonist candesartan cilexetil and ACE-inhibitors in patients with congestive heart failure.

INTRODUCTION: Combination of ACE-inhibitors with angiotensin-II type 1 receptor antagonists could provide better blockade of RAAS system compared with monotherapy. OBJECTIVE: The aim of this study was to evaluate hemodynamic and neurohumoral effects at rest and during exercise of Candesartan cilexetil as add-on therapy to ACE-inhibitors in patients with heart failure NYHA class III to IV. METHODS: This was a prospective, randomized, double-blind, placebo-controlled, parallel group study. Thirty-five patients received either Candesartan 8 mg/16 mg (1st and 2nd week/ of 3-24) or placebo as add-on therapy to their previous ACE-inhibitor during a 24-weeks treatment period. RESULTS: Peak aerobic capacity remained constant in the Candesartan group of patients (0.06 +/- 1.43 mL/min/ kg) and slightly decreased in the placebo group (-1.10 +/- 1.51 mL/min/kg), without a statistically significant difference between the groups (p = 0.13). Exercise time showed a relevant increase in the Candesartan (31.9 +/- 58.5 sec) and a significant decrease in the placebo group (-25.9 +/- 85.9 sec) compared to baseline value. The difference between the studied groups was statistically significant (p < 0.001). Relevant differences between the two groups were observed in the changes of right atrial pressure at rest (Candesartan: -1.9 +/- 1.7 mmHg, placebo: 1.0 +/- 2.7 mmHg, p < 0.01), pulmonary capillary wedge pressure at rest (Candesartan: -3.1 +/- 3.8 mmHg, placebo: 0.2 +/- 4.6 mmHg, p < 0.05) and systemic vascular resistance at maximum exercise (Candesartan: -141.9 +/- 253.3 dyne*sec/cm5, placebo: 47.3 +/-221.0 dyne*sec/cm5, p < 0.05). CONCLUSION: The efficacy of CHF treatment of congestive heart failure was moderately improved by Candesartan as add-on therapy to ACE-inhibitors.