Hua Zen Ling

Expansion of the red cell distribution width and evolving iron deficiency as predictors of poor outcome in chronic heart failure.

BACKGROUND An elevated red cell distribution width (RDW) and iron deficiency (ID) at baseline predict enhanced mortality in chronic heart failure (CHF), but little is known about the prognostic implications of their temporal trends. We sought to determine the survival implications of temporal changes in RDW and evolving ID in patients with CHF. METHODS The relation between red cell indices on first consultation and over time with mortality in 274 stable patients with systolic CHF was analysed. The combination of a rising RDW with a falling mean cell volume (MCV) over time defined evolving ID. RESULTS Over a median 12 month period, 51% and 23% of patients had a rise in RDW and evolving ID, respectively. After a median follow-up of 27 months, 60 (22%) patients died. A rising RDW predicted enhanced all-cause mortality (unadjusted HR for 1% per week rise 9.27, 95% CI 3.58 to 24.00, P<0.0001) independently and incrementally to baseline RDW, with an absolute increase >0.02% per week optimally predictive. Evolving ID also related to higher rates of mortality (HR 2.78, 95% CI 1.64 to 4.73, P<0.001) and was prognostically worse than a rising RDW alone (P<0.005). Patients with evolving ID who maintained their Hb levels over time had a 2-fold greater risk of death than those whose Hb levels declined without evolving ID. CONCLUSIONS An expanding RDW and evolving iron deficiency over time predict an amplified risk of death in CHF and should be utilised for risk stratification and/or therapeutically targeted to potentially improve outcomes.

Calculated plasma volume status and prognosis in chronic heart failure

Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non‐invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients.

010 Multicentre validation of the adverse prognostic implications of declining serum albumin levels in chronic heart failure

Background Single-centre studies have shown that a low serum albumin at baseline forecasts enhanced mortality in chronic heart failure (CHF) possibly because it reflects aberrations (eg, inflammation, impaired nutrition, plasma volume expansion) that can exacerbate disease. We hypothesised that attenuations in serum albumin over time would be prognostically more ominous than baseline values, and would be so even in a multicentre setting. Methods We analysed the survival implications of baseline albumin and ∆albumin in a derivation cohort of 246 CHF outpatients (mean [±SD] age 68±12 years, LVEF 29±8%, 48% NYHA class >2) from University College London Hospital and then in a validation cohort of 148 CHF outpatients (age 69±12 years, LVEF 28±10%, 41% NYHA class >2) from Imperial Healthcare (St Marys Hospital and Hammersmith Hospital, London). Results In the derivation cohort, 51 (21%) patients died over 13 months. Baseline albumin independently predicted mortality (HR 0.89, 95% CI 0.84 to 0.94, χ2:18, p<0.0001). However, ∆albumin (unadjusted HR 0.89, 95% CI 0.84 to 0.92, χ2:53, p<0.0001) was even more predictive (Difference in ROC AUC for baseline vs ∆albumin 0.16, p<0.001) and did so independently of all covariates including baseline albumin. A reduction in albumin > 6 g/l optimally predicted death (ROC AUC 0.82, p<0.0001) and conferred a sixfold escalated risk of mortality (HR 6.42, 95% CI 3.67 to 11.22, p<0.0001). In incremental prognostic analyses, the addition of ∆albumin to the strongest four variable model (baseline albumin, NYHA class, ∆urea, ∆haemoglobin) dramatically augmented the χ2 value (43 vs 84, p<0.0001). In the validation cohort, 43 (30%) patients died. ∆albumin (unadjusted HR 0.89, 95% CI 0.86 to 0.92, χ2: 44, p<0.0001) was again prognostically superior to baseline albumin with a fall >6 g/l predicting an ∼sixfold increased risk (HR 5.64, 95% CI 3.08 to 10.31, χ2: 35, p<0.0001). Addition of ∆albumin to the strongest three variable model (baseline red cell distribution width, ∆red cell distribution width, ∆urea) also augmented the χ2 value (51 vs 65, p<0.001). Conclusions A fall in serum albumin over time consistently predicts an amplified risk of death in systolic CHF and enables simple and cheap risk stratification.

107 Expansion of the red cell distribution width and evolving iron deficiency as predictors of poor outcome in chronic heart failure

Background Red cell distribution width (RDW) is a surrogate of many aberrations (inflammation, malnutrition, iron deficiency (ID)) that may drive chronic heart failure (CHF) progression. While an elevated RDW and iron deficiency at baseline predict mortality in CHF, little is known about the prognostic implications of their temporal trends. Methods We analysed the relation of red cell indices on first consultation and over time with mortality in 274 outpatients with CHF (mean (±SD) age 70±14 years, LVEF 28±8%, NYHA class 2±1, 54% ischaemic). The combination of a rising RDW and a falling mean cell volume (MCV) identified evolving ID. Results On initial consultation, an RDW >15%, Hb<12.5 g/dl, and MCV <80 fl were evident in 41%, 46%, and 8% of patients. Over a median (±IQR) follow-up of 15±17 months, 60 (22%) patients died. On Cox proportional hazards analyses, a higher RDW independently predicted increased mortality (HR 1.21, p<0.0001). Over time, 51%, 58%, 40%, and 23% of patients had a rise in RDW, a fall in Hb, a fall in MCV, and evolving ID, respectively. A rising RDW predicted death (HR 1.18, p=0.002) independently of baseline RDWs and changes in Hb, with an absolute increase >1% conferring a twofold escalated risk of mortality (Abstract 107 figure 1A). Evolving ID was also associated with poorer survival (HR 2.89, p<0.0001, Abstract 107 figure 1B).Abstract 107 Figure 1 Conclusions An expanding RDW and evolving iron deficiency over time predict an amplified risk of death in CHF and could be utilised for risk stratification or therapeutically targeted to improve outcomes.

104 Prognostic utility of calculated plasma volume status in chronic heart failure

Background Plasma volume (PV) expansion is a hallmark feature of worsening heart failure that is notoriously underestimated by clinical examination. While radioisotope assays optimally quantify PV status, numerous haemodialysis-based equations also exist for its estimation. The prognostic utility of such formulas in chronic heart failure (CHF) is unknown. Methods We analysed the relation between estimated PV status and mortality in 246 outpatients with CHF (mean (±SD) age 67±13 years, NYHA class 2±1, LVEF 28±8%). PV status was calculated (Hakim RM, et al) by subtracting the patients actual PV ((1-haematocrit) × (a + (b × weight)); a and b are gender-specific constants) from their ideal PV ((c × weight); c=gender-specific constant). Results Median (±IQR) PV status was—261±550 ml with 78% and 21% of patients having PV contraction and expansion, respectively. Patients with PV excess had significantly higher creatinine and lower albumin levels. Over a median follow-up of 13±16 months, 36 (15%) patients died. PV status predicted mortality (HR 1.001, 95% CI 1.001 to 1.002, p=0.001) in a graded fashion (Abstract 104 figure 1A) and did so independently of NYHA class, LVEF, weight, haematocrit and creatinine. A PV status ≤−178 ml optimally predicted survival (ROC AUC 0.68, p=0.0007) and conferred a 75% reduced hazard for death (HR 0.16, 95% CI 0.07 to 0.37, p<0.0001, Abstract 104 figure 1B).Abstract 104 Figure 1 Conclusions Calculating plasma volume status in CHF patients appears prognostically useful and suggests that dehydration is better tolerated than volume excess in these individuals and that targeting therapy to achieve a plasma volume status ≤178 ml might increment survival.