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In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting.

The approval of new heart failure (HF) therapies has slowed over the past two decades in part due to the high costs of conducting large randomized clinical trials that are needed to adequately power major clinical endpoint studies. Several biomarkers have been identified reflecting different elements of HF pathophysiology, with possible applications in diagnosis, risk stratification, treatment monitoring, and even in the design of clinical trials. Biomarkers could potentially be used to refine study inclusion criteria to enable enrolment of patients who are more likely to respond to a therapeutic intervention, despite being at sufficient risk to meet pre-determined study endpoint rates. When there is a close relationship between biomarker levels and clinical endpoints, changes in biomarker levels after a given treatment can act as a surrogate endpoint, potentially reducing the duration and cost of a clinical trial. Natriuretic peptides have been widely used in clinical trials with a variable amount of added value, which such variation being probably due to the absence of a close pathophysiological connection to the study drug. Notable exceptions to this include sacubitril/valsartan and vericiguat. Future studies should seek to adopt unbiased approaches for discovery of true companion diagnostics; with -omics-based tools, biomarkers might be more precisely selected for use in clinical trials to identify responses that closely reflect the biological effects of the drug under investigation. Finally, biomarkers associated with cardiac damage and remodelling, such as cardiac troponin, could be employed as safety endpoints provided that standardization between different assays is achieved.

Cardiac amyloidosis (CA) is now recognized as an important cause of heart failure. Increased wall thickness and diastolic dysfunction of the left ventricle are the most easily detectable manifestations of CA, but amyloid accumulates in all cardiac structures. Involvement of the left and right atria may be due to the haemodynamic effects of ventricular diastolic dysfunction, the effects of amyloid infiltration into the atrial wall, and the cardiotoxic damage of atrial cardiomyocytes by amyloid precursors. Atrial amyloidosis is an early manifestation of CA, and is associated with an increased risk of atrial fibrillation and thromboembolic events. Furthermore, atrial amyloidosis can be found even in the absence of systemic disease and ventricular involvement. This condition is named isolated atrial amyloidosis and is due to a local overproduction of atrial natriuretic peptide. In this review we summarize the evidence on the mechanisms and clinical relevance of atrial amyloidosis.

Aims Systolic pulmonary artery pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and TAPSE/SPAP ratio trajectories are not fully characterized in chronic heart failure (HF). We assessed very long-term longitudinal SPAP, TAPSE and TAPSE/SPAP trajectories in HF patients, and their dynamic changes in outcomes. Methods and results Prospective, consecutive, observational registry of real-life HF patients, performing echocardiography studies at baseline and according to a prospectively structured schedule after 1 year, and then every 2 years, up to 15 years. Pulmonary hypertension (PH) was defined as SPAP >= 40 mmHg; right ventricular dysfunction (RVD) was defined at TAPSE

Background Coronary artery disease remains a major cause of death despite better outcomes of ST-segment-elevation myocardial infarction (STEMI). We aimed to analyze data from the Ruti-STEMI registry of in-hospital, 28-day, and 1-year events in patients with STEMI over the past 3 decades in Catalonia, Spain, to assess trends in STEMI prognosis. Methods and Results Between February 1989 and December 2017, a total of 7589 patients with STEMI were admitted consecutively. Patients were grouped into 5 periods: 1989 to 1994 (period 1), 1995 to 1999 (period 2), 2000 to 2004 (period 3), 2005 to 2009 (period 4), and 2010 to 2017 (period 5). We used Cox regression to compare 28-day and 1-year STEMI mortality and in-hospital complication trends across these periods. Mean patient age was 61.6 +/- 12.6 years, and 79.3% were men. The 28-day all-cause mortality declined from period 1 to period 5 (10.4% versus 6.0%;P

Aims Better management of heart failure (HF) over the past two decades has improved survival, mainly by reducing the incidence of death due to cardiovascular (CV) causes. Deaths due to non-CV causes, particularly cancer, may be increasing. This study explored the modes of death of consecutive patients who attended a HF clinic over 17 years. Methods and results A total of 935 deaths were ascertained from 2002 to 2018 among 1876 patients (mean age 65.8 +/- 12.5 years, 75% men, left ventricular ejection fraction < 50%) admitted to our HF clinic. Median follow-up was 4.2 years [1.9-7.8]. Mode of death was curated from patient health records and verified by the Catalan and Spanish health system databases. Trends for every mode of death were assessed by polynomial regression. Two trends were observed: a significant reduction in sudden death (P = 0.03) without changes in HF progression as mode of death (P = 0.26), and a significant increase in non-CV modes of death (P < 0.001). Non-CV deaths accounted for 17.4% of deaths in 2002 and 65.8% of deaths in 2018. A total 138 deaths were due to cancer (37% of non-CV deaths). A significant trend was observed towards a progressive increase in cancer deaths over time (P = 0.002). The main mode of cancer mortality was lung cancer. Conclusions The modes of death in HF have shifted over the last two decades. Patients with HF die less due to sudden death and more due to non-CV causes, mainly cancer. Whether HF triggers cancer, or cancer develops in HF survivors, deserves further insight.

Background-Although frailty has been associated with increased risks for hospitalization and mortality in chronic heart failure, the precise average effect remains uncertain. We performed a systematic review and meta-analysis to summarize the hazards for mortality and incident hospitalization in patients with heart failure and frailty compared with those without frailty and explored the heterogeneity underlying the effect size estimates. Methods and Results-MEDLINE, EMBASE, and Cochrane databases were queried for articles published between January 1966 and March 2018. Predefined selection criteria were used. Hazard ratios (HRs) were pooled for meta-analyses, and where odds ratios were used previously, original data were recalculated for HR. Overlapping data were consolidated, and only unique data points were used. Study quality and bias were assessed. Eight studies were included for mortality (2645 patients), and 6 studies were included for incident hospitalization (2541 patients) during a median follow-up of 1.82 and 1.12 years, respectively. Frailty was significantly associated with an increased hazard for mortality (HR, 1.54; 95% confidence interval, 1.34-1.75; P

Background Methods Pulmonary hypertension (PH) is a common cause of right ventricular (RV) remodeling and functional tricuspid regurgitation (FTR), but incremental pulmonary artery systolic pressure (PASP) does not always correlate with anatomic and functional RV changes. This study aimed to evaluate a noninvasive measure of pulmonary vascular resistance (PVR) for predicting RV dilatation, RV dysfunction, and severity of FTR. We prospectively analyzed consecutive stable patients with PASP >= 35 mm Hg or any degree of RV dilatation or dysfunction secondary to PH. Noninvasive PVR was calculated based on FTR peak velocity and flow in RV outflow tract. Results Conclusions We included 251 patients, aged 72.1 +/- 11.4 years, 53% women, 74.9% with type 2 pulmonary hypertension. The mean PASP was 48.3 +/- 12.2 mm Hg. Both PASP and PVR significantly correlated with FTR, RV dilatation, and RV systolic dysfunction. After dichotomizing FTR and RV dilatation and systolic dysfunction as nonsignificant vs significant, FTR and RV dilatation were similarly predicted by PASP and PVR, but RV dysfunction was better predicted by PVR (AUC = 0.78 [0.72-0.84] vs 0.66 [0.60-0.73] for PASP, P < 0.001). Patients with low PASP but high PVR showed worse RV and left ventricular function but lower rates of right heart failure and smaller inferior vena cava, compared to patients with high PASP but low PVR. Noninvasive PVR was superior to PASP for predicting RV systolic dysfunction, but both were similarly associated with RV dilatation or FTR grade. PASP and PVR complement each other to define the echocardiographic findings and clinical status of the patient.

Aims Significant recovery of left ventricular ejection fraction (LVEF) occurs in a proportion of patients with heart failure (HF) and reduced ejection fraction (HFrEF). We analysed outcomes, including mortality [all-cause, cardiovascular (CV), HF-related, and sudden death], and HF-related hospitalizations in this HF-recovered group. The primary endpoint was a composite of CV death or HF hospitalization. Methods and results LVEF was assessed at baseline and at 1 year in 1057 consecutive HF patients. Patients were classified into three groups: (i) HF-recovered: LVEF < 45% at baseline and >= 45% at 1 year (n = 233); (ii) HF with preserved EF (HFpEF): LVEF = 45% throughout follow-up (n = 117); and (iii) HFrEF: LVEF < 45% throughout follow-up (n = 707). Mean follow-up was 5.6 +/- 3.1 years. HF-recovered patients differed from HFrEF and HFpEF groups in demographic and clinical characteristics. The mean LVEF increase was 21.1 +/- 10 points in HF-recovered patients. Using the HF-recovered group as a reference, the risks for the primary composite endpoint (n = 376), with non-CV death as competing risk, for HFpEF and HFrEF groups were: hazard ratio (HR) 2.33 [95% confidence interval (CI) 1.60-3.39], P < 0.001 and HR 1.99 (95% CI 1.50-2.65), P < 0.001, respectively. All-cause (n = 429), CV (n = 245), HF-related (n = 127), and sudden death (n = 60) were significantly lower in HF-recovered subjects relative to HFrEF (all P < 0.01). HF-recovered patients also experienced less recurrent HF hospitalizations (P < 0.001). Conclusion One in four treated patients with HFrEF showed recovery of systolic function. HF-recovered patients had significantly improved mortality and morbidity relative to HFpEF and HFrEF subjects. Further research is needed to identify optimal medications and device indications for HF-recovered patients.