February 2019 At a Glance: Pathophysiology, Exercise Capacity, Diuretics and Valve Disease

Obesity may cause a distinct phenotype of heart failure (HF) with preserved ejection (HFpEF), characterized by plasma volume expansion, cardiac chamber overfilling and reduced ventricular compliance.1 Milton Packer has proposed a clinical classification of obese patients with HFpEF based on plasma volume status, left ventricular (LV) dimensions and natriuretic peptide levels.2 This classification may provide a framework for better targeted treatment of obese HFpEF patients. Adrenomedullin, a peptide synthesized by endothelial and vascular smooth muscle cells, has natriuretic and vasodilatory effects and preserves endothelial barrier function, inhibiting vascular leakage.3 In his review, Voors et al.4 summarize its characteristics and describe a novel immunoassay measuring its biological activity as well as adrecizumab, a humanized, monoclonal, non-neutralizing, adrenomedullin-binding antibody with a half-life of 15 days. Adrecizumab cannot cross the endothelial barrier and thus, when infused, can bind circulating adrenomedullin and drain it from the interstitium into the circulation, thus enhancing its intravascular effects.4 Pulmonary hypertension is a major determinant of outcomes in cardiac patients.5-7 Weber et al.8 assessed its prevalence and prognostic impact in 503 patients with severe aortic stenosis undergoing cardiac catheterization prior to aortic valve replacement. Pulmonary hypertension was found at baseline in 48% of patients, 29% had isolated post-capillary hypertension, 6% isolated pre-capillary hypertension, and 13% combined pre- and post-capillary pulmonary hypertension. This latter group had higher pulmonary wedge pressure, lower pulmonary artery capacitance, larger left atrial size, more severe mitral regurgitation and poorer survival at multivariate analysis.8 Cardiopulmonary exercise testing has a major role for the prognostic assessment of HF patients.9 Paolillo et al.10 examined the change during the last 20 years in its prognostic value in 6083 patients enrolled in the MECKI score database. A progressively better survival was found for the patients studied in the years 2006–2010, compared to those studied in the years 1993–2000 and 2001–2005, with no further improvement afterwards. A concomitant reduction in peak oxygen consumption and minute ventilation to carbon dioxide slope cut-off values for increased mortality was also observed.10 The prognostic value of the 6-minute walk test (6MWT) distance was analysed in the patients enrolled in the systems BIOlogy Study to TAilored Treatment in Chronic HF (BIOSTAT-CHF).11 Patients in the lowest and middle 6MWT tertile had poorer outcomes, compared to those in the highest tertile (>360 m) [adjusted hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.38-2.18]. Also a decrease in the 6MWT after 9 months was associated with a worse prognosis (adjusted HR for each 50 m decrease 1.09, 95% CI 1.06–1.12). The 6MWT distance was not changed by treatment up-titration.11 Diuretic treatment maintains a pivotal role for the treatment of HF. A position paper by the Heart Failure Association of the European Society of Cardiology summarizes our knowledge regarding the assessment of congestion in HF patients, diuretics' mechanisms of action and how to better use them in the treatment of acute and chronic HF.12 Percutaneous treatment of functional mitral regurgitation may potentially broaden the indication to the correction of this abnormality in HF patients.7, 13 Adamo et al.14 studied the role of LV reverse remodelling, defined as a ≥ 10% reduction in LV end-systolic volume from baseline to 6 months, in the prediction of outcomes of 184 consecutive HF patients undergoing the MitraClip procedure. LV reverse remodelling was observed in 42.9% of patients. These patients were more likely to be females, less likely to have an ischaemic aetiology or a prior HF hospitalization, and had smaller LV dimensions. LV reverse remodelling was associated with a lower adjusted risk of death (HR 0.44, 95% CI 0.20–0.96), and of the composite endpoint of death or HF hospitalization (HR 0.54, 95% CI 0.32–0.92).14 Keßler et al.15 analysed the predictors of 1-year rehospitalization for decompensated HF in 355 consecutive patients who underwent MitraClip implantation. The rate of HF hospitalization decreased from 52.7% in the year before the procedure to 18.0% in the first year after implantation. Baseline LV ejection fraction, troponin T and New York Heart Association class were independent predictors of 1-year rehospitalization after MitraClip implantation. Rehospitalization was associated with a 2.3 and 3.3 increased risk of subsequent cardiovascular and all-cause mortality, respectively.15 Wagenaar et al.16 studied the effects on self-care of two web-based systems, the heartfailurematters.org website and the e-health adjusted care pathway, compared to usual care, using a prospective, randomized, controlled design. After 3 months of follow-up, the mean score on the self-care scale was significantly higher in the website-based groups. The effect attenuated, up to no differences between groups, after 1 year. Palliative care of patients with advanced HF is still underused in most of the hospitals.17, 18 Straw et al.19 used the Surprise Question: ‘would you be surprised if this patient were to die within the next year?’ to predict mortality in 129 patients with acute HF. The Surprise Question showed excellent sensitivity (85%) and negative predictive value (88%), but limited specificity (59%) and positive predictive value (52%). Thus, it can identify nearly all patients who are within the last year of life as well as those unlikely to die and can be used for the selection of patients for palliative therapy.