April 2018 at a Glance: Focus on Prognostic Variables

Bhambhani et al.1 pooled data from four community-based longitudinal cohorts, including 28 820 subjects free of heart failure (HF) at entry and followed for 12 years, to identify predictive variables for the development of HF with mid-range ejection fraction (HFmrEF), compared with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF). Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, prior myocardial infarction, natriuretic peptides, cystatin-C, and high-sensitivity troponin. Natriuretic peptides were also the strongest predictors of HFrEF. All-cause mortality following the onset of HFmrEF was similar to that of HFrEF and worse than that of HFpEF.1 Similarities between HFmrEF and HFrEF are therefore confirmed with respect to their risk factors, whereas the outcome of HFmrEF patients has been often found as better compared to that of HFrEF patients.2 Delles et al.3 studied by nuclear magnetic resonance-based metabolomics two cohorts of subjects at risk of cardiovascular events and identified, among 80 metabolites, phenylalanine as a predictor of incident HF hospitalizations. Although its additive predictive value was modest, it remained significant after adjustment for baseline variables and natriuretic peptide plasma levels. Vaduganathan et al.4 assessed plasma renin activity in 1306 patients with HFrEF enrolled in ASTRONAUT (Aliskiren Trial on Acute Heart Failure Outcomes). Although aliskiren treatment reduced plasma renin activity, the changes in this biomarker were not associated with any difference in outcomes and no interaction with the effects of treatment was found. This study is another example of how favourable changes in measurements related with survival may not be predictive of treatment efficacy, a major limitation for the use of smaller trials to predict the effects on outcomes.5, 6 Sokoreli et al.7 evaluated prognostic variables in 671 patients hospitalized for HF. In addition to traditional demographic data and laboratory measurements, psychosocial factors, namely frailty, depression and anxiety, have independent prognostic value, consistently with other recent studies.8, 9 The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score performed better than the HF Survival Score (HFSS) and Seattle HF Model (SHFM) in 6112 patients with HFrEF in terms of prediction of the combined endpoint of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation.10 Ghio et al.11 performed right heart catheterization and acute vasodilator challenge in 156 patients with HFrEF and pulmonary hypertension (PH) classified as combined post-capillary and pre-capillary PH (Cpc-PH, n=106) vs. isolated post-capillary PH (Ipc-PH, n=50). Acute vasodilator administration caused a larger improvement in pulmonary vascular resistance, diastolic pulmonary gradient and transpulmonary gradient in patients with Cpc-PH than in those with Ipc-PH. However, patients with Cpc-PH who maintained a lower pulmonary arterial compliance remained in an unfavourable portion of the inverse hyperbolic relationship between pulmonary vascular resistance and pulmonary arterial compliance. Patients with Cpc-PH and those not responding to haemodynamic challenge had more severe right ventricular dysfunction and a poorer survival.11 These data confirm and extend those showing the importance of dynamic assessment of pulmonary pressures and of right ventricular function in patients with chronic HFrEF.12, 13 An analysis of 146 patients with acutely decompensated HF showed similar evidence of venous congestion, with enlarged inferior vena cava, right and left atria, and right ventricular dysfunction in patients with either HFpEF or HFrEF, despite lower plasma levels of brain natriuretic peptides in patients with HFpEF.14 Siegismund et al.15 analysed endomyocardial biopsies from 54 consecutive patients with amyloidosis. Patients with cardiac amyloid light-chain (AL) amyloidosis had a poorer prognosis than those with transthyretin amyloidosis (ATTR) and outcome was significantly worse in those with concomitant signs of inflammation shown by quantitative immunohistology. Many variables may influence the effects of cardiac resynchronization therapy (CRT) on outcomes.16-18 Greater benefits were shown in women. Linde et al.19 performed an individual-patient data meta-analysis of five randomized controlled trials and showed that height and QRS duration, but not sex, were independent predictors of CRT benefit.