Is red distribution width a valid tool to predict impaired iron transport in heart failure?

Background: Impaired iron transport (IIT) is a form of iron deficiency (ID) defined as transferrin saturation (TSAT) < 20% irrespective of serum ferritin levels. It is frequently observed in heart failure (HF) where it negatively affects prognosis irrespective of anaemia. Objectives: In this retrospective study we searched for a surrogate biomarker of IIT. Methods: We tested the predictive power of red distribution width (RDW), mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) to detect IIT in 797 non-anaemic HF patients. Results: At ROC analysis, RDW provided the best AUC (0.6928). An RDW cut-off value of 14.2% identified patients with IIT, with positive and negative predictive values of 48 and 80%, respectively. Comparison between the true and false negative groups showed that estimated glomerular filtration rate (eGFR) was significantly higher (p = 0.0092) in the true negative vs. false negative group. Therefore, we divided the study population according to eGFR value: 109 patients with eGFR ≥ 90 ml/min/1.73 m2, 318 patients with eGFR 60-89 ml/min/1.73 m2, 308 patients with eGFR 30-59 ml/min/1.73 m2 and 62 patients with eGFR < 30 ml/min/1.73 m2. In the first group, positive and negative predictive values were 48 and 81% respectively, 51 and 85% in the second group, 48 and 73% in the third group and 43 and 67% in the fourth group. Conclusion: RDW may be seen as a reliable marker to exclude IIT in non-anaemic HF patients with eGFR ≥60 ml/min/1.73 m2.

Revisiting a Prognosticating Algorithm from Cardiopulmonary Exercise Testing in Chronic Heart Failure (from the MECKI Score Population).

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with ß blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3 years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without ß blockers, whereas those with ß-blockers had 11% (p <0.0001). In patients without ß blockers, 36%, 24%, and 7% CV events were observed in those with peak VO2 ≤10, with peak VO2 >10 <18, and with peak VO2 ≥18 ml/kg/min (p = 0.0001), respectively; in MECKI patients with peak VO2 ≤10 and patients with intermediate exercise capacity, a peak respiratory exchange ratio (≥1.15) and VE/VCO2 slope (≥35) were diriment, respectively (p = 0.0001). EOV, when occurred, increased risk. In MECKI patients on ß blockers, 29%, 17%, and 8% CV events were noticed in those with a peak VO2 ≤8, with peak VO2 = 8 to 12, and patients with peak VO2 ≥12 ml/kg/min, respectively (p = 0.0000); when EOV was monitored an increment of risk was witnessed. In conclusion, the outcome of this algorithm was confirmed with the MECKI cohort.

Role of impaired iron transport on exercise performance in heart failure patients.

AIMS: Impaired iron transport (IIT) occurs frequently in heart failure (HF) patients, even in the absence of anaemia and it is associated with a poor quality of life and prognosis. The impact of IIT on exercise capacity, as assessed by the cardiopulmonary exercise test (CPET), in HF is at present unknown. The aim of this article is to evaluate in HF patients the impact on exercise performance of IIT, defined as transferrin saturation (TSAT) <20%. METHODS AND RESULTS: We collected data of 676 patients hospitalized for HF. All underwent laboratory analysis, cardiac ultrasound, and CPET. Patients were grouped by the presence/absence of IIT and anaemia (haemoglobin <13 and <12 g/dL in male and female, respectively): Group 1 (G1) no anaemia, no IIT; Group 2 (G2) anaemia, no IIT; Group 3 (G3) no anaemia, IIT; Group 4 (G4) anaemia and IIT. Peak oxygen uptake (peakVO2) reduced from G1 to G3 and from G2 to G4 (G1: 1266 ± 497 mL/min, G2: 1011 ± 385 mL/min, G3: 1041 ± 395 mL/min, G4: 833 ± 241 mL/min), whereas the ventilation to carbon dioxide relationship slope (VE/VCO2 slope) increased (G1: 31.8 ± 7.5, G2: 34.5 ± 7.4, G3: 36.1 ± 10.2, G4: 37.5 ± 8.4). At multivariate regression analysis, peakVO2 independent predictors were anaemia, brain natriuretic peptide (BNP), and left ventricular ejection fraction, whereas VE/VCO2 slope independent predictors were IIT and BNP. CONCLUSION: In HF IIT is associated with exercise performance impairment independently from anaemia, and it is a predictor of elevated VE/VCO2 slope, a pivotal index of HF prognosis.

Increased serum uric acid level predicts poor prognosis in mildly severe chronic heart failure with reduced ejection fraction. An analysis from the MECKI score research group.

BACKGROUND: Hyperuricemia prognostic impact on clinical outcomes in chronic heart failure (HF) patients has been investigated with inconclusive results. OBJECTIVES: Aim of the study was to evaluate the prognostic impact of serum uric acid (SUA) on long-term clinical outcomes in HF. METHODS: An analysis of MECKI (Metabolic Exercise Cardiac Kidney Index) database, with median follow-up of 3.4 years. RESULTS: Relation between SUA and all-cause/ cardiovascular (CV) deaths have been analysed in 4,577 patients (3,688 males, age 62.7 ±â€¯12.9 years), with reduced ejection fraction HF (35 ± 11%), peakVO2 1151 ± 440 ml/min; NYHA class I-II (72.6%), III-IV (27.4%). SUA was associated with increased total and CV mortality (HR 1.120 and HR 1.128, respectively p < 0.0001), also after adjustment for peakVO2, VE/VCO2 slope, diuretic use and MECKI score. SUA was significantly associated with CV mortality only in NYHA class I-II (HR 1.17, p < 0.0001) while there was no association in class III-IV (HR 1.03, p = NS). No prognostic added values of SUA with respect to the MECKI score was observed at the ROC analysis. CONCLUSIONS: SUA is confirmed to be associated with increased mortality, but in less severe HF only. However SUA did not show additional prognostic power to the MECKI score.