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Aims: To evaluate the effect of long‐term tafamidis treatment on health‐related quality of life (HRQoL) in patients with transthyretin amyloid cardiomyopathy (ATTR‐CM) enrolled in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR‐ACT) and long‐term extension (LTE) study. Methods and results: We examined change from baseline in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ‐OS) and clinical summary (KCCQ‐CS) scores in patients who received tafamidis meglumine 80 mg for 30 months in ATTR‐ACT and tafamidis (meglumine 80 mg or bioequivalent free acid 61 mg) for 30 months in the LTE study, and in patients who received placebo for 30 months in ATTR‐ACT and tafamidis for 30 months in the LTE study. In ATTR‐ACT, 176 and 177 patients were randomized to tafamidis 80 mg and placebo, respectively. Patients who continuously received tafamidis had a 6‐ to 7‐point reduction in least squares (LS) mean (standard error) KCCQ‐OS and KCCQ‐CS scores at month 30 (−6.25 [1.53] and −7.48 [1.39]), with little or no further decline over the next 30 months (−5.92 [1.77] and −9.21 [1.88] at month 60). Patients who received placebo in ATTR‐ACT had a 20‐point reduction in LS mean KCCQ‐OS and KCCQ‐CS scores at month 30 (−19.60 [1.94] and −19.90 [2.01]), but the decline slowed after initiating tafamidis (−24.70 [3.04] and −25.30 [3.36] at month 60). Conclusion: Tafamidis reduced HRQoL decline in patients with ATTR‐CM. Patients continuously treated with tafamidis for 60 months demonstrated stabilized HRQoL. In patients who initially received placebo in ATTR‐ACT, tafamidis reduced the decline in HRQoL during the LTE study. [ABSTRACT FROM AUTHOR]

This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population. [ABSTRACT FROM AUTHOR]

Aims: The European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT-R) was set up with the aim of describing the clinical epidemiology and the 1-year outcomes of patients with heart failure (HF) with the added intention of comparing differences between participating countries.Methods and Results: The ESC-HF-LT-R is a prospective, observational registry contributed to by 211 cardiology centres in 21 European and/or Mediterranean countries, all being member countries of the ESC. Between May 2011 and April 2013 it collected data on 12 440 patients, 40.5% of them hospitalized with acute HF (AHF) and 59.5% outpatients with chronic HF (CHF). The all-cause 1-year mortality rate was 23.6% for AHF and 6.4% for CHF. The combined endpoint of mortality or HF hospitalization within 1 year had a rate of 36% for AHF and 14.5% for CHF. All-cause mortality rates in the different regions ranged from 21.6% to 36.5% in patients with AHF, and from 6.9% to 15.6% in those with CHF. These differences in mortality between regions are thought reflect differences in the characteristics and/or management of these patients.Conclusion: The ESC-HF-LT-R shows that 1-year all-cause mortality of patients with AHF is still high while the mortality of CHF is lower. This registry provides the opportunity to evaluate the management and outcomes of patients with HF and identify areas for improvement. [ABSTRACT FROM AUTHOR]

Aims: The European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT-R) was set up with the aim of describing the clinical epidemiology and the 1-year outcomes of patients with heart failure (HF) with the added intention of comparing differences between participating countries. Methods and results: The ESC-HF-LT-R is a prospective, observational registry contributed to by 211 cardiology centres in 21 European and/or Mediterranean countries, all being member countries of the ESC. Between May 2011 and April 2013 it collected data on 12 440 patients, 40.5% of them hospitalized with acute HF (AHF) and 59.5% outpatients with chronic HF (CHF). The all-cause 1-year mortality rate was 23.6% for AHF and 6.4% for CHF. The combined endpoint of mortality or HF hospitalization within 1 year had a rate of 36% for AHF and 14.5% for CHF. All-cause mortality rates in the different regions ranged from 21.6% to 36.5% in patients with AHF, and from 6.9% to 15.6% in those with CHF. These differences in mortality between regions are thought reflect differences in the characteristics and/or management of these patients. Conclusion: The ESC-HF-LT-R shows that 1-year all-cause mortality of patients with AHF is still high while the mortality of CHF is lower. This registry provides the opportunity to evaluate the management and outcomes of patients with HF and identify areas for improvement. [ABSTRACT FROM AUTHOR]

Background: The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation. Methods: The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus. Results: A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided. Conclusions: The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues. [ABSTRACT FROM AUTHOR]

The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of cardiac allograft vasculopathy, similar to the development of the system for adjudication of cardiac allograft rejection by histology. [Copyright &y& Elsevier]

Crespo-Leiro MG, Delgado JF, Paniagua MJ, Vázquez, de Prada JA, Fernandez-Yañez J, Almenar L, Diaz-Molina B, Roig E, Arizón JM, Alonso-Pulpón L, Garrido IP, Sanz ML, de la Fuente L, Mirabet S, Manito N, Muñiz J. Prevalence and severity of renal dysfunction among 1062 heart transplant patients according to criteria based on serum creatinine and estimated glomerular filtration rate: results from the CAPRI study. Clin Transplant 2010: 24: E88–E93. © 2009 John Wiley & Sons A/S. Chronic kidney disease (CKD) is staged on the basis of glomerular filtration rate; generally, the MDRD study estimate, eGFR, is used. Renal dysfunction (RD) in heart transplant (HT) patients is often evaluated solely in terms of serum creatinine (SCr). In a cross-sectional, 14-center study of 1062 stable adult HT patients aged 59.1 ± 12.5 yr (82.3% men), RD was graded as absent-or-mild (AoM), moderate, or severe (this last including dialysis and kidney graft) by two classifications: SCr-RD (SCr cutoffs 1.6 and 2.5 mg/dL) and eGFR-RD (eGFR cutoffs 60 and 30 mL/min/1.73 m2). SCr-RD was AoM in 68.5% of patients, moderate in 24.9%, and severe in 6.7%; eGFR-RD, AoM in 38.6%, moderate in 52.2%, severe in 9.2%. Among patients evaluated <2.7, 2.7-6.2, 6.2-9.5 and >9.5 yr post-HT (the periods defined by time-since-transplant quartiles), AoM/moderate/severe RD prevalences were <2.7, SCr-RD 74/21/5%, eGFR-RD 47/47/6%; 2.7-6.2, SCr-RD 73/22/5%, eGFR-RD 37/56/7%; 6.2–9.5, SCr-RD 69/24/7%, eGFR-RD 37/54/9%; >9.5, SCr-RD 58/32/10%, eGFR-RD 32/52/16%. The prevalence of severe RD increases with time since transplant. If the usual CKD stages are appropriate for HT patients, the need for less nephrotoxic immunosuppressants and other renoprotective measures is greater than is suggested by direct SCr-based grading, which should be abandoned as excessively insensitive. [ABSTRACT FROM AUTHOR]

Background: Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. Methods: This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti–interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. Results: Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. Conclusions: Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively. [Copyright &y& Elsevier]

Background: Anticoagulation in heart transplant (HT) recipients increases the risk of hemorrhagic complications, so correct reversal of anticoagulation is needed. Dabigatran, a direct thrombin inhibitor, is increasingly used for anticoagulation in patients with non‐valvular atrial fibrillation (NVAF) whose effect can be reversed by idarucizumab. Aim: To present a nationwide experience using idarucizumab for the urgent reversal of dabigatran before HT. Methods: Multicenter observational study in 12 Spanish centers to analyze the clinical outcomes after using idarucizumab before HT surgery. Results: Fifty‐three patients were included (81.1% male). 7.5% required re‐operation in the immediate postoperative period to control bleeding and 66% transfusion of blood products. Median length of stay in the intensive care unit was 6 days and total hospital stay 24 days. 30‐day survival was 92.4%. There were four deaths in the first month, all in the first 5 days post‐HT. Only in one patient (transplanted due to a congenital heart disease, after sternotomy) who had surgical problems and right ventricular failure post‐HT death was associated with bleeding. Conclusions: These results may support the use of dabigatran as an alternative to vitamin K antagonists in patients listed for HT requiring anticoagulation due to NVAF. More studies are needed to reaffirm these observations. [ABSTRACT FROM AUTHOR]

Aims: We assessed the interplay between hyperkalaemia (HK) and renin-angiotensin-aldosterone system inhibitor (RAASi) use, dose and discontinuation, and their association with all-cause or cardiovascular death in patients with chronic heart failure (HF). We hypothesized that HK-associated increased death may be related to RAASi withdrawal.Methods and Results: The ESC-HFA-EORP Heart Failure Long-Term Registry was used. Among 9222 outpatients (HF with reduced ejection fraction: 60.6%, HF with mid-range ejection fraction: 22.9%, HF with preserved ejection fraction: 16.5%) from 31 countries, 16.6% had HK (≥5.0 mmol/L) at baseline. Angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) was used in 88.3%, a mineralocorticoid receptor antagonist (MRA) in 58.7%, or a combination in 53.2%; of these, at ≥50% of target dose in ACEi: 61.8%; ARB: 64.7%; and MRA: 90.3%. At a median follow-up of 12.2 months, there were 789 deaths (8.6%). Both hypokalaemia and HK were independently associated with higher mortality, and ACEi/ARB prescription at baseline with lower mortality. MRA prescription was not retained in the model. In multivariable analyses, HK at baseline was independently associated with MRA non-prescription at baseline and subsequent discontinuation. When considering subsequent discontinuation of RAASi (instead of baseline use), HK was no longer found associated with all-cause deaths. Importantly, all RAASi (ACEi, ARB, or MRA) discontinuations were strongly associated with mortality.Conclusions: In HF, hyper- and hypokalaemia were associated with mortality. However, when adjusting for RAASi discontinuation, HK was no longer associated with mortality, suggesting that HK may be a risk marker for RAASi discontinuation rather than a risk factor for worse outcomes. [ABSTRACT FROM AUTHOR]

Aims: Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes.Methods and Results: We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66 ± 13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25-80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363-419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12-2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96-1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33-1.07; P = 0.083) and cardiovascular mortality (HR 0.62, 95% CI 0.38-1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01-1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09-0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29-0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37-0.87; P = 0.008) were independently associated with successful decrease.Conclusion: Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease. [ABSTRACT FROM AUTHOR]

Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many—sometimes contradictory—observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device. [ABSTRACT FROM AUTHOR]

Aims: To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post‐discharge outcomes. Methods and results: Of 8298 patients in the European Society of Cardiology Heart Failure Long‐Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non‐use of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and beta‐blockers. In‐hospital death occurred in 3.3%. The prevalence of hyponatraemia and in‐hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in‐hospital mortality 6.9%), 11% Yes/No (in‐hospital mortality 4.9%), 8% No/Yes (in‐hospital mortality 4.7%), and 72% No/No (in‐hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In‐hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12‐month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35–1.89), Yes/No 1.35 (1.14–1.59), and No/Yes 1.18 (0.96–1.45). For death or heart failure hospitalization they were 1.38 (1.21–1.58), 1.17 (1.02–1.33), and 1.09 (0.93–1.27), respectively. Conclusion: Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in‐hospital and post‐discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk. [ABSTRACT FROM AUTHOR]

Aim: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common in patients with heart failure (HF). The aim of this study was to investigate prevalence, clinical characteristics and outcomes of patients with or without isolated or combined MR and TR across the entire HF spectrum. Methods and results: The ESC‐HFA EORP HF Long‐Term Registry is a prospective, multicentre, observational study including patients with HF and 1‐year follow‐up data. Outpatients without aortic valve disease were included and stratified according to isolated or combined moderate/severe MR and TR. Among 11 298 patients, 7541 (67%) had no MR/TR, 1931 (17%) isolated MR, 616 (5.5%) isolated TR and 1210 (11%) combined MR/TR. Baseline characteristics were differently distributed across MR/TR categories. Compared to HF with reduced ejection fraction, HF with mildly reduced ejection fraction was associated with a lower risk of isolated MR (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.60–0.80), and distinctly lower risk of combined MR/TR (OR 0.51; 95% CI 0.41–0.62). HF with preserved ejection fraction (HFpEF) was associated with a distinctly lower risk of isolated MR (OR 0.42; 95% CI 0.36–0.49), and combined MR/TR (OR 0.59; 95% 0.50–0.70), but a distinctly increased risk of isolated TR (OR 1.94; 95% CI 1.61–2.33). All‐cause death, cardiovascular death, HF hospitalization and combined outcomes occurred more frequently in combined MR/TR, isolated TR and isolated MR versus no MR/TR. The highest incident rates were observed in isolated TR and combined MR/TR. Conclusion: In a large cohort of outpatients with HF, prevalence of isolated and combined MR and TR was relatively high. Isolated TR was driven by HFpEF and was burdened by an unexpectedly poor outcome. [ABSTRACT FROM AUTHOR]

Aims: To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). Methods and results: Data from the prospective ESC HFA EORP HF Long‐Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end‐diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23–1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07–1.74) but not AR (adjusted HR 1.13, 95% CI 0.96–1.33) were independently associated with the 12‐month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. Conclusions: In the ESC HFA EORP HF Long‐Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in‐hospital mortality and 12‐month composite outcome, regardless of ejection fraction category. [ABSTRACT FROM AUTHOR]

This clinical consensus statement reviews the use of inotropic support in patients with advanced heart failure. The current guidelines only support use of inotropes in the setting of acute decompensated heart failure with evidence of organ malperfusion or shock. However, inotropic support may be reasonable in other patients with advanced heart failure without acute severe decompensation. The clinical evidence supporting use of inotropes in these situations is reviewed. Particularly, patients with persistent congestion, systemic hypoperfusion, or advanced heart failure with need for palliation, and specific situations relevant to implantation of left ventricular assist devices or heart transplantation are discussed. Traditional and novel drugs with inotropic effects are discussed and use of guideline‐directed therapy during inotropic support is reviewed. Finally, home inotropic therapy is described, and palliative care and end‐of‐life aspects are reviewed in relation to management of ongoing inotropic support (including guidance for maintenance and weaning of chronic inotropic therapy support). [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to assess long-term safety of intravenous cardiovascular agents-vasodilators, inotropes and/or vasopressors-in acute heart failure (AHF).Methods and Results: The European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) registry was a prospective, observational registry conducted in 21 countries. Patients with unscheduled hospitalizations for AHF (n = 6926) were included: 1304 (18.8%) patients received a combination of intravenous (i.v.) vasodilators and diuretics, 833 (12%) patients received i.v. inotropes and/or vasopressors. Primary endpoint was long-term all-cause mortality. Main secondary endpoints were in-hospital and post-discharge mortality. Adjusted hazard ratio (HR) showed no association between the use of i.v. vasodilator and diuretic and long-term mortality [HR 0.784, 95% confidence interval (CI) 0.596-1.032] nor in-hospital mortality (HR 1.049, 95% CI 0.592-1.857) in the matched cohort (n = 976 paired patients). By contrast, adjusted HR demonstrated a detrimental association between the use of i.v. inotrope and/or vasopressor and long-term all-cause mortality (HR 1.434, 95% CI 1.128-1.823), as well as in-hospital mortality (HR 1.873, 95% CI 1.151-3.048) in the matched cohort (n = 606 paired patients). No association was found between the use of i.v. inotropes and/or vasopressors and long-term mortality in patients discharged alive (HR 1.078, 95% CI 0.769-1.512). A detrimental association with inotropes and/or vasopressors was seen in all geographic regions and, among catecholamines, dopamine was associated with the highest risk of death (HR 1.628, 95% CI 1.031-2.572 vs. no inotropes).Conclusions: Vasodilators did not demonstrate any association with long-term clinical outcomes, while inotropes and/or vasopressors were associated with increased risk of all-cause death, mostly related to excess of in-hospital mortality in AHF. [ABSTRACT FROM AUTHOR]

Aims: The objectives of the present study were to describe epidemiology and outcomes in ambulatory heart failure (HF) patients stratified by left ventricular ejection fraction (LVEF) and to identify predictors for mortality at 1 year in each group.Methods and Results: The European Society of Cardiology Heart Failure Long-Term Registry is a prospective, observational study collecting epidemiological information and 1-year follow-up data in 9134 HF patients. Patients were classified according to baseline LVEF into HF with reduced EF [EF <40% (HFrEF)], mid-range EF [EF 40-50% (HFmrEF)] and preserved EF [EF >50% (HFpEF)]. In comparison with HFpEF subjects, patients with HFrEF were younger (64 years vs. 69 years), more commonly male (78% vs. 52%), more likely to have an ischaemic aetiology (49% vs. 24%) and left bundle branch block (24% vs. 9%), but less likely to have hypertension (56% vs. 67%) or atrial fibrillation (18% vs. 32%). The HFmrEF group resembled the HFrEF group in some features, including age, gender and ischaemic aetiology, but had less left ventricular and atrial dilation. Mortality at 1 year differed significantly between HFrEF and HFpEF (8.8% vs. 6.3%); HFmrEF patients experienced intermediate rates (7.6%). Age, New York Heart Association (NYHA) class III/IV status and chronic kidney disease predicted mortality in all LVEF groups. Low systolic blood pressure and high heart rate were predictors for mortality in HFrEF and HFmrEF. A lower body mass index was independently associated with mortality in HFrEF and HFpEF patients. Atrial fibrillation predicted mortality in HFpEF patients.Conclusions: Heart failure patients stratified according to different categories of LVEF represent diverse phenotypes of demography, clinical presentation, aetiology and outcomes at 1 year. Differences in predictors for mortality might improve risk stratification and management goals. [ABSTRACT FROM AUTHOR]

Aims: The 'obesity paradox' is consistently observed in patients with heart failure (HF). We investigated the relationship of body surface area (BSA) to mortality and hospitalizations in patients with chronic HF.Methods and Results: Data from the outpatient cohort of the observational, prospective, Heart Failure Long-Term Registry of the Heart Failure Association of the European Society of Cardiology was analysed in order to evaluate the prognostic significance of BSA in chronic HF. A total of 9104 chronic HF patients (age 64.8 ± 13.4 years; 71.6% males) were enrolled. Mortality during 1-year follow-up was observed in 718 of 8875 (8.1%) patients. A progressive, inverse relationship between all-cause mortality and BSA levels was observed; the adjusted hazard ratio (HR) for 1-year mortality was 1.823 [95% confidence interval (CI) 1.398-2.376], P < 0.001 for the lowest quartile of BSA <1.78 m(2) , and 1.255, 95% CI 1.000-1.576, P = 0.05 for the middle two quartiles (1.78 ≤BSA ≤2.07 m(2) ), compared with the highest quartile (BSA >2.07 m(2) ). For each increase of 0.1 m(2) in BSA, an adjusted HR of 0.908 (95% CI 0.870-0.948), P < 0.001 for mortality was calculated. HF hospitalizations were not associated with BSA subgroup distribution. In both genders, subjects within the lowest BSA quartile (males <1.84 m(2) and females <1.64 m(2) ) had significantly higher mortality rates during follow-up (log-rank P < 0.0001). However, the stepwise association with mortality was more distinct in males.Conclusions: Total and cardiovascular mortality, but not HF hospitalizations was inversely associated with BSA levels in chronic HF patients. BSA may serve as a prognostic indicator for adverse outcome in HF patients. [ABSTRACT FROM AUTHOR]

Aims: The 'obesity paradox' is consistently observed in patients with heart failure (HF).We investigated the relationship of body surface area (BSA) to mortality and hospitalizations in patients with chronic HF. Methods and results: Data from the outpatient cohort of the observational, prospective, Heart Failure Long-Term Registry of the Heart Failure Association of the European Society of Cardiology was analysed in order to evaluate the prognostic significance of BSA in chronic HF. A total of 9104 chronic HF patients (age 64.8±13.4 years; 71.6% males) were enrolled. Mortality during 1-year follow-up was observed in 718 of 8875 (8.1%) patients. A progressive, inverse relationship between all-cause mortality and BSA levels was observed; the adjusted hazard ratio (HR) for 1-year mortality was 1.823 [95% confidence interval (CI) 1.398-2.376], P < 0.001 for the lowest quartile of BSA <1.78m², and 1.255, 95% CI 1.000-1.576, P = 0.05 for the middle two quartiles (1.78 ≼BSA ≼2.07m2), compared with the highest quartile (BSA >2.07m²). For each increase of 0.1m² in BSA, an adjusted HR of 0.908 (95% CI 0.870-0.948), P < 0.001 for mortality was calculated. HF hospitalizations were not associated with BSA subgroup distribution. In both genders, subjects within the lowest BSA quartile (males <1.84m² and females <1.64m²) had significantly higher mortality rates during follow-up (log-rank P < 0.0001). However, the stepwise association with mortality was more distinct in males. Conclusions Total and cardiovascular mortality, but not HF hospitalizations was inversely associated with BSA levels in chronic HF patients. BSA may serve as a prognostic indicator for adverse outcome in HF patients. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) applied to selected patients with heart failure (HF) improves their prognosis. In recent years, eligibility criteria for CRT have regularly changed. This study aimed to investigate the changes in eligibility of real-life HF patients for CRT over the past fifteen years. We reviewed European and North American guidelines from this period and applied them to HF patients from the ESC-HF Pilot and ESC-Long-Term Registries. Taking into consideration the criteria assessed in this study (including all classes of recommendations i.e., class I, IIa and IIb, as well as patients with AF and SR), the 2013 (ESC) guidelines would have qualified the most patients for CRT (266, 18.3%), while the 2015 (ESC) guidelines would have qualified the least (115, 7.9%; p-value for differences between all analyzed papers <0.0001). There were only 26 patients (1.8%) who would be eligible for CRT using the class I recommendations across all of the guidelines. These results demonstrate the variability in recommendations for CRT over the years. Moreover, this data indicates underuse of this form of pacing in HF and highlights the need for more studies in order to improve the outcomes of HF patients and further personalize their management. [ABSTRACT FROM AUTHOR]

Aims: To perform a comprehensive characterization of acute heart failure (AHF) with preserved (HFpEF), versus mildly reduced (HFmrEF) versus reduced ejection fraction (HFrEF). Methods and results: Of 5951 participants in the ESC HF Long‐Term Registry hospitalized for AHF (acute coronary syndromes excluded), 29% had HFpEF, 18% HFmrEF, and 53% HFrEF. Hospitalization reasons were most commonly atrial fibrillation (more in HFmrEF and HFpEF), followed by ischaemia (HFmrEF), infection (HFmrEF and HFpEF), worsening renal function (HFrEF), and uncontrolled hypertension (HFmrEF and HFpEF). Hospitalization characteristics included lower blood pressure, more oedema and higher natriuretic peptides with lower ejection fraction, similar pulmonary congestion, more mitral regurgitation in HFrEF and HFmrEF and more tricuspid regurgitation in HFrEF. In‐hospital mortality was 3.4% in HFrEF, 2.1% in HFmrEF and 2.2% in HFpEF. Intravenous diuretic (∼80%) and nitrate (∼15%) use was similar but inotrope use greater in HFrEF (16%, vs. HFmrEF 7.4% vs. HFpEF 5.3%). Weight loss and estimated glomerular filtration rate improvement were greater in HFrEF, whereas reduction in natriuretic peptides was similar. Over 1 year post‐discharge, events per 100 patient‐years (95% confidence interval) in HFrEF versus HFmrEF versus HFpEF were: all‐cause death 22 (20–24) versus 17 (14–20) versus 17 (15–20); cardiovascular (CV) death 12 (10–13) versus 8.6 (6.6–11) versus 8.4 (6.9–10); non‐CV death 2.4 (1.8–3.1) versus 3.3 (2.1–4.8) versus 4.5 (3.5–5.9); all‐cause hospitalization 48 (45–51) versus 35 (31–40) versus 42 (39–46); HF hospitalization 29 (27–32) versus 19 (16–22) versus 17 (15–20); and non‐CV hospitalization 7.7 (6.6–8.9) versus 9.6 (7.5–12) versus 15 (13–17). Conclusion: In AHF, HFrEF is more severe and has greater in‐hospital mortality. Post‐discharge, HFrEF has greater CV risk, HFpEF greater non‐CV risk, and HFmrEF lower overall risk. [ABSTRACT FROM AUTHOR]

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed. [ABSTRACT FROM AUTHOR]

Document Reviewers: Rudolf A. de Boer (CPG Review Coordinator) (Netherlands), P. Christian Schulze (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Johann Bauersachs (Germany), Antoni Bayes-Genis (Spain), Michael A. Borger (Germany), Werner Budts (Belgium), Maja Cikes (Croatia), Kevin Damman (Netherlands), Victoria Delgado (Netherlands), Paul Dendale (Belgium), Polychronis Dilaveris (Greece), Heinz Drexel (Austria), Justin Ezekowitz (Canada), Volkmar Falk (Germany), Laurent Fauchier (France), Gerasimos Filippatos (Greece), Alan Fraser (United Kingdom), Norbert Frey (Germany), Chris P. Gale (United Kingdom), Finn Gustafsson (Denmark), Julie Harris (United Kingdom), Bernard Iung (France), Stefan Janssens (Belgium), Mariell Jessup (United States of America), Aleksandra Konradi (Russia), Dipak Kotecha (United Kingdom), Ekaterini Lambrinou (Cyprus), Patrizio Lancellotti (Belgium), Ulf Landmesser (Germany), Christophe Leclercq (France), Basil S. Lewis (Israel), Francisco Leyva (United Kingdom), AleVs Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Lars H. Lund (Sweden), Donna Mancini (United States of America), Josep Masip (Spain), Davor Milicic (Croatia), Christian Mueller (Switzerland), Holger Nef (Germany), Jens-Cosedis Nielsen (Denmark), Lis Neubeck (United Kingdom), Michel Noutsias (Germany), Steffen E. Petersen (United Kingdom), Anna Sonia Petronio (Italy), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Dimitrios J. Richter (Greece), Evgeny Schlyakhto (Russia), Petar Seferovic (Serbia), Michele Senni (Italy), Marta Sitges (Spain), Miguel Sousa-Uva (Portugal), Carlo G. Tocchetti (Italy), Rhian M. Touyz (United Kingdom), Carsten Tschoepe (Germany), Johannes Waltenberger (Germany/Switzerland) All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/guidelines For the Supplementary Data which include background information and detailed discussion of the data that have provided the basis for the guidelines see European Heart Journal online. [ABSTRACT FROM AUTHOR]

Cold ischemia time (CIT) has been associated to heart transplantation (HT) prognosis. However, there is still uncertainty regarding the CIT cutoff value that might have relevant clinical implications. We analyzed all adults that received a first HT during the period 2008–2018. CIT was defined as the time between the cross-clamp of the donor aorta and the reperfusion of the heart. Primary outcome was 1-month mortality. We included 2629 patients, mean age was 53.3 ± 12.1 years and 655 (24.9%) were female. Mean CIT was 202 ± 67 min (minimum 20 min, maximum 600 min). One-month mortality per CIT quartile was 9, 12, 13, and 19%. One-year mortality per CIT quartile was 16, 19, 21, and 28%. CIT was an independent predictor of 1-month mortality, but only in the last quartile of CIT >246 min (odds ratio 2.1, 95% confidence interval 1.49–3.08, p <.001). We found no relevant differences in CIT during the study period. However, the impact of CIT in 1-month and 1-year mortality decreased with time (p value for the distribution of ischemic time by year 0.01), particularly during the last 5 years. Although the impact of CIT in HT prognosis seems to be decreasing in the last years, CIT in the last quartile (>246 min) is associated with 1-month and 1-year mortality. Our findings suggest the need to limit HT with CIT > 246 min or to use different myocardial preservation systems if the expected CIT is >4 h. • There is still uncertainty regarding the cold ischemia time cutoff value that is relevant to heart transplantation prognosis • The prognostic impact of cold ischemia time seems to be decreasing but times > 4 h are associated with poor prognosis • Our data suggest the need to use different myocardial preservation systems if the expected cold ischemia time is >4 h [ABSTRACT FROM AUTHOR]

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and results: Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N‐terminal pro‐B‐type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC‐HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m2 (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation. [ABSTRACT FROM AUTHOR]

Background: Transplant recipients are chronically ill patients, who require lifelong follow-up to manage co-morbidities and prevent graft loss. This necessitates a system of care that is congruent with the Chronic Care Model. The eleven-item self-report Patient Assessment of Chronic Illness Care (PACIC) scale assesses whether chronic care is congruent with the Chronic Care Model, yet its validity for heart transplant patients has not been tested.Methods: We tested the validity of the English version of the PACIC, and compared the similarity of the internal structure of the PACIC across English-speaking countries (USA, Canada, Australia and United Kingdom) and across six languages (French, German, Dutch, Spanish, Italian and Portuguese). This was done using data from the cross-sectional international BRIGHT study that included 1378 heart transplant patients from eleven countries across 4 continents. To test the validity of the instrument, confirmatory factor analyses to check the expected unidimensional internal structure, and relations to other variables, were performed.Results: Main analyses confirmed the validity of the English PACIC version for heart transplant patients. Exploratory analyses across English-speaking countries and languages also confirmed the single factorial dimension, except in Italian and Spanish.Conclusion: This scale could help healthcare providers monitor level of chronic illness management and improve transplantation care.Trial Registration: Clinicaltrials.gov ID: NCT01608477, first patient enrolled in March 2012, registered retrospectively: May 30, 2012. [ABSTRACT FROM AUTHOR]

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure. • Inotropes increase cardiac output mainly by enhancing cardiac contractility. • Inotropes indicated for heart failure are beta-agonists, milrinone, levosimendan. • Inotropes should only be used in low-output acute or advanced heart failure. • Identifying patients with low-output heart failure is often challenging. • Inotrope selection should be individually tailored. [ABSTRACT FROM AUTHOR]

Aims: To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM-HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes.Methods and Results: Outpatients with HFrEF in the ESC-EORP-HFA Long-Term Heart Failure (HF-LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM-HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM-HF and guideline criteria, respectively. Absent PARADIGM-HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub-optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub-optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM-HF and guidelines. One-year heart failure hospitalization was higher (12% and 17% vs. 12%) and all-cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM-HF.Conclusions: Among outpatients with HFrEF in the ESC-EORP-HFA HF-LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM-HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM-HF enalapril group. [ABSTRACT FROM AUTHOR]

Aims: Classification of acute heart failure (AHF) patients into four clinical profiles defined by evidence of congestion and perfusion is advocated by the 2016 European Society of Cardiology (ESC)guidelines. Based on the ESC-EORP-HFA Heart Failure Long-Term Registry, we compared differences in baseline characteristics, in-hospital management and outcomes among congestion/perfusion profiles using this classification.Methods and Results: We included 7865 AHF patients classified at admission as: 'dry-warm' (9.9%), 'wet-warm' (69.9%), 'wet-cold' (19.8%) and 'dry-cold' (0.4%). These groups differed significantly in terms of baseline characteristics, in-hospital management and outcomes. In-hospital mortality was 2.0% in 'dry-warm', 3.8% in 'wet-warm', 9.1% in 'dry-cold' and 12.1% in 'wet-cold' patients. Based on clinical classification at admission, the adjusted hazard ratios (95% confidence interval) for 1-year mortality were: 'wet-warm' vs. 'dry-warm' 1.78 (1.43-2.21) and 'wet-cold' vs. 'wet-warm' 1.33 (1.19-1.48). For profiles resulting from discharge classification, the adjusted hazard ratios (95% confidence interval) for 1-year mortality were: 'wet-warm' vs. 'dry-warm' 1.46 (1.31-1.63) and 'wet-cold' vs. 'wet-warm' 2.20 (1.89-2.56). Among patients discharged alive, 30.9% had residual congestion, and these patients had higher 1-year mortality compared to patients discharged without congestion (28.0 vs. 18.5%). Tricuspid regurgitation, diabetes, anaemia and high New York Heart Association class were independently associated with higher risk of congestion at discharge, while beta-blockers at admission, de novo heart failure, or any cardiovascular procedure during hospitalization were associated with lower risk of residual congestion.Conclusion: Classification based on congestion/perfusion status provides clinically relevant information at hospital admission and discharge. A better understanding of the clinical course of the two entities could play an important role towards the implementation of targeted strategies that may improve outcomes. [ABSTRACT FROM AUTHOR]

We previously reported a microarray-based diagnostic system for heart transplant endomyocardial biopsies (EMBs), using either 3-archetype (3AA) or 4-archetype (4AA) unsupervised algorithms to estimate rejection. In the present study we examined the stability of machine-learning algorithms in new biopsies, compared 3AA vs 4AA algorithms, assessed supervised binary classifiers trained on histologic or molecular diagnoses, created a report combining many scores into an ensemble of estimates, and examined possible automated sign-outs. We studied 889 EMBs from 454 transplant recipients at 8 centers: the initial cohort (N = 331) and a new cohort (N = 558). Published 3AA algorithms derived in Cohort 331 were tested in Cohort 558, the 3AA and 4AA models were compared, and supervised binary classifiers were created. A'lgorithms derived in Cohort 331 performed similarly in new biopsies despite differences in case mix. In the combined cohort, the 4AA model, including a parenchymal injury score, retained correlations with histologic rejection and DSA similar to the 3AA model. Supervised molecular classifiers predicted molecular rejection (areas under the curve [AUCs] >0.87) better than histologic rejection (AUCs <0.78), even when trained on histology diagnoses. A report incorporating many AA and binary classifier scores interpreted by 1 expert showed highly significant agreement with histology (p < 0.001), but with many discrepancies, as expected from the known noise in histology. An automated random forest score closely predicted expert diagnoses, confirming potential for automated signouts. Molecular algorithms are stable in new populations and can be assembled into an ensemble that combines many supervised and unsupervised estimates of the molecular disease states. [ABSTRACT FROM AUTHOR]

Exercise training (ET) and secondary prevention measures in cardiovascular disease aim to stimulate early physical activity and to facilitate recovery and improve health behaviours. ET has also been proposed for heart failure patients with a ventricular assist device (VAD), to help recovery in the patient's functional capacity. However, the existing evidence in support of ET in these patients remains limited. After a review of current knowledge on the causes of the persistence of limitation in exercise capacity in VAD recipients, and concerning the benefit of ET in VAD patients, the Heart Failure Association of the European Society of Cardiology has developed the present document to provide practical advice on implementing ET. This includes appropriate screening to avoid complications and then starting with early mobilisation, ET prescription is individualised to meet the patient's needs. Finally, gaps in our knowledge are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Heart transplant (HTx) recipients need to follow a complex therapeutic regimen. We assessed the international prevalence and variability in nonadherence to six nonpharmacologic treatment components (physical activity, sun protection, diet, alcohol use, nonsmoking, and outpatient follow‐up visits). Methods: We used self‐report data of 1397 adult HTx recipients from the 36‐HTx‐center, 11‐country, 4‐continent, cross‐sectional BRIGHT study (ClinicalTrials.gov ID: NCT01608477). The nonadherence definitions used were as follows: Physical activity: <3 times/wk 20 minutes’ vigorous activity, <5 times/wk 30 minutes’ moderate activity, or <5 times/wk a combination of either intensity; Sun protection: not “always” applying any sun protection; Diet: not “often” or “always” following recommended diet(s); Alcohol use: >1 alcoholic drink/d (women) or >2 drinks/d (men); Smoking: current smokers or stopped <1 year before; Follow‐up visits: missing ≥1 of the last 5 outpatient follow‐up visits. Overall prevalence figures were adjusted to avoid over‐ or underrepresentation of countries. Between‐country variability was assessed within each treatment component via chi‐square testing. Results: The adjusted study‐wide nonadherence prevalence figures were as follows: 47.8% for physical activity (95% CI [45.2‐50.5]), 39.9% for sun protection (95% CI [37.3‐42.5]), 38.2% for diet recommendations (95% CI [35.1‐41.3]), 22.9% for alcohol consumption (95% CI [20.8‐25.1]), 7.4% for smoking cessation (95% CI [6.1‐8.7]), and 5.7% for follow‐up visits (95% CI [4.6‐6.9]). Significant variability was observed between countries in all treatment components except follow‐up visits. Conclusion: Nonadherence to the post‐HTx nonpharmacologic treatment regimen is prevalent and shows significant variability internationally, suggesting a need for tailored adherence‐enhancing interventions. [ABSTRACT FROM AUTHOR]

Despite the successes from refined peri-operative management techniques and immunosuppressive therapies, antibodies remain a serious cause of morbidity and mortality for patients both before and after heart transplantation. Patients awaiting transplant who possess antibodies against human leukocyte antigen are disadvantaged by having to wait longer to receive an organ from a suitably matched donor. The number of pre-sensitized patients has been increasing, a trend that is likely due to the increased use of mechanical circulatory support devices. Even patients who are not pre-sensitized can go on to produce donor-specific antibodies after transplant, which are associated with worse outcomes. The difficulty in managing antibodies is uncertainty over which antibodies are of clinical relevance, which patients to treat, and which treatments are most effective and safe. There is a distinct lack of data from prospective trials. An international consensus conference was organized and attended by 103 participants from 75 centers to debate contentious issues, determine the best practices, and formulate ideas for future research on antibodies. Prominent experts presented state-of-the-art talks on antibodies, which were followed by group discussions, and then, finally, a reconvened session to establish consensus where possible. Herein we address the discussion, consensus points, and research ideas. [ABSTRACT FROM AUTHOR]

Background: As medication non-adherence is a major risk factor for poor post-transplant outcomes, we explored how adherence is assessed, enhanced and integrated across the transplant continuum. Aim: The aim of this study was to study practice patterns regarding pre- and post-transplant medication adherence assessment and interventions in international heart transplant centres. Methods: We used data from the Building Research Initiative Group: chronic illness management and adherence in heart transplantation (BRIGHT) study, a cross-sectional study conducted in 36 heart transplant centres in 11 countries. On a 27-item questionnaire, 100 clinicians (range one to five per centre) reported their practice patterns regarding adherence assessment and intervention strategies pre-transplant, immediately post-transplant, less than one year, and one or more year post-transplant. Educational/cognitive, counselling/behavioural and psychosocial/affective strategies were assessed. Clinicians’ responses (intervention present vs. absent; or incongruence in reporting intervention) were aggregated at the centre level. Results: The adherence assessment method most commonly used along the transplant continuum was questioning patients (range 75–88.9%). Pre-transplant, all three categories of intervention strategy were applied. Providing reading materials (82.9%) or instructions (68.6%), involving family or support persons in education (91.4%), and establishing partnership (91.4%) were used most frequently. Post-transplant, strategies closely resembled those employed pre-transplant. Training patients (during recovery) and cueing were more often applied during hospitalisation (74.3%). After the first year post-transplant, except for motivational interviewing (25.7–28.6%), the number of strategies decreased. Conclusions: Across the transplant continuum, diverse adherence interventions are implemented; however, post-transplant, the frequency of adherence interventions decreases. Therefore, increased investment is necessary in long-term adherence interventions. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to assess long-term safety of intravenous cardiovascular agents--vasodilators, inotropes and/or vasopressors--in acute heart failure (AHF). Methods and results The European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) registry was a prospective, observational registry conducted in 21 countries. Patients with unscheduled hospitalizations for AHF (n=6926) were included: 1304 (18.8%) patients received a combination of intravenous (i.v.) vasodilators and diuretics, 833 (12%) patients received i.v. inotropes and/or vasopressors. Primary endpoint was long-term all-cause mortality. Main secondary endpoints were in-hospital and post-discharge mortality. Adjusted hazard ratio (HR) showed no association between the use of i.v. vasodilator and diuretic and long-term mortality [HR 0.784, 95% confidence interval (CI) 0.596-1.032] nor in-hospital mortality (HR 1.049, 95% CI 0.592-1.857) in the matched cohort (n=976 paired patients). By contrast, adjusted HR demonstrated a detrimental association between the use of i.v. inotrope and/or vasopressor and long-term all-cause mortality (HR 1.434, 95% CI 1.128-1.823), as well as in-hospital mortality (HR 1.873, 95% CI 1.151-3.048) in the matched cohort (n=606 paired patients). No association was found between the use of i.v. inotropes and/or vasopressors and long-term mortality in patients discharged alive (HR 1.078, 95% CI 0.769-1.512). A detrimental association with inotropes and/or vasopressors was seen in all geographic regions and, among catecholamines, dopamine was associated with the highest risk of death (HR 1.628, 95% CI 1.031-2.572 vs. no inotropes). Conclusions Vasodilators did not demonstrate any association with long-term clinical outcomes, while inotropes and/or vasopressors were associated with increased risk of all-cause death, mostly related to excess of in-hospital mortality in AHF. [ABSTRACT FROM AUTHOR]

Traditionally, the main indication for cardiopulmonary exercise testing (CPET) in heart failure (HF) was for the selection of candidates to heart transplantation: CPET was mainly performed in middle-aged male patients with HF and reduced left ventricular ejection fraction. Today, CPET is used in broader patients' populations, including women, elderly, patients with co-morbidities, those with preserved ejection fraction, or left ventricular assistance device recipients, i.e. individuals with different responses to incremental exercise and markedly different prognosis. Moreover, the diagnostic and prognostic utility of symptom-limited CPET parameters derived from submaximal tests is more and more considered, since many patients are unable to achieve maximal aerobic power. Repeated tests are also being used for risk stratification and evaluation of intervention, so that these data are now available. Finally, patients, physicians and healthcare decision makers are increasingly considering how treatments might impact morbidity and quality of life rather than focusing more exclusively on hard endpoints (such as mortality) as was often the case in the past. Innovative prognostic flowcharts, with CPET at their core, that help optimize risk stratification and the selection of management options in HF patients, have been developed. [ABSTRACT FROM AUTHOR]

Background: In Spain, listing for high-urgent heart transplantation is allowed for critically ill candidates not weanable from temporary mechanical circulatory support (T-MCS). We sought to analyse the clinical outcomes of this strategy.Methods and Results: We conducted a case-by-case, retrospective review of clinical records of 291 adult patients listed for high-urgent heart transplantation under temporary devices from 2010 to 2015 in 16 Spanish institutions. Survival after listing and adverse clinical events were studied. At the time of listing, 169 (58%) patients were supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO), 70 (24%) on temporary left ventricular assist devices (T-LVAD) and 52 (18%) on temporary biventricular assist devices (T-BiVAD). Seven patients transitioned from VA-ECMO to temporary ventricular assist devices while on the waiting list. Mean time on T-MCS was 13.1 ± 12.6 days. Mean time from listing to transplantation was 7.6 ± 8.5 days. Overall, 230 (79%) patients were transplanted and 54 (18.6%) died during MCS. In-hospital postoperative mortality after transplantation was 33.3%, 11.9% and 26.2% for patients bridged on VA-ECMO, T-LVAD and T-BiVAD, respectively (P = 0.008). Overall survival from listing to hospital discharge was 54.4%, 78.6% and 55.8%, respectively (P = 0.002). T-LVAD support was independently associated with a lower risk of death over the first year after listing (hazard ratio 0.52, 95% confidence interval 0.30-0.92). Patients treated with VA-ECMO showed the highest incidence rate of adverse clinical events associated with T-MCS.Conclusion: Temporary devices may be used to bridge critically ill candidates directly to heart transplantation in a setting of short waiting list times, as is the case of Spain. In our series, bridging with T-LVAD was associated with more favourable outcomes than bridging with T-BiVAD or VA-ECMO. [ABSTRACT FROM AUTHOR]

Background In Spain, listing for high-urgent heart transplantation is allowed for critically ill candidates not weanable from temporary mechanical circulatory support (T-MCS). We sought to analyse the clinical outcomes of this strategy. Methods and results We conducted a case-by-case, retrospective review of clinical records of 291 adult patients listed for high-urgent heart transplantation under temporary devices from 2010 to 2015 in 16 Spanish institutions. Survival after listing and adverse clinical events were studied. At the time of listing, 169 (58%) patients were supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO), 70 (24%) on temporary left ventricular assist devices (T-LVAD) and 52 (18%) on temporary biventricular assist devices (T-BiVAD). Seven patients transitioned from VA-ECMO to temporary ventricular assist devices while on the waiting list. Mean time on T-MCS was 13.1±12.6 days. Mean time from listing to transplantation was 7.6±8.5 days. Overall, 230 (79%) patients were transplanted and 54 (18.6%) died during MCS. In-hospital postoperative mortality after transplantation was 33.3%, 11.9% and 26.2% for patients bridged on VA-ECMO, T-LVAD and T-BiVAD, respectively (P =0.008). Overall survival from listing to hospital discharge was 54.4%, 78.6% and 55.8%, respectively (P =0.002). T-LVAD support was independently associated with a lower risk of death over the first year after listing (hazard ratio 0.52, 95% confidence interval 0.30-0.92). Patients treated with VA-ECMO showed the highest incidence rate of adverse clinical events associated with T-MCS. Conclusion Temporary devices may be used to bridge critically ill candidates directly to heart transplantation in a setting of short waiting list times, as is the case of Spain. In our series, bridging with T-LVAD was associated with more favourable outcomes than bridging with T-BiVAD or VA-ECMO. [ABSTRACT FROM AUTHOR]

AimsThe objectives of the present study were to describe epidemiology and outcomes in ambulatory heart failure (HF) patients stratified by left ventricular ejection fraction (LVEF) and to identify predictors for mortality at 1 year in each group. Methods and results The European Society of Cardiology Heart Failure Long-Term Registry is a prospective, observational study collecting epidemiological information and 1-year follow-up data in 9134 HF patients. Patients were classified according to baseline LVEF into HF with reduced EF [EF <40% (HFrEF)], mid-range EF [EF 40–50% (HFmrEF)] and preserved EF [EF >50% (HFpEF)]. In comparison with HFpEF subjects, patients with HFrEF were younger (64 years vs. 69 years), more commonly male (78% vs. 52%), more likely to have an ischaemic aetiology (49% vs. 24%) and left bundle branch block (24% vs. 9%), but less likely to have hypertension (56% vs. 67%) or atrial fibrillation (18% vs. 32%). The HFmrEF group resembled the HFrEF group in some features, including age, gender and ischaemic aetiology, but had less left ventricular and atrial dilation. Mortality at 1 year differed significantly between HFrEF and HFpEF (8.8% vs. 6.3%); HFmrEF patients experienced intermediate rates (7.6%). Age, New York Heart Association (NYHA) class III/IV status and chronic kidney disease predicted mortality in all LVEF groups. Low systolic blood pressure and high heart rate were predictors for mortality in HFrEF and HFmrEF. A lower body mass index was independently associated with mortality in HFrEF and HFpEF patients. Atrial fibrillation predicted mortality in HFpEF patients. Conclusions Heart failure patients stratified according to different categories of LVEF represent diverse phenotypes of demography, clinical presentation, aetiology and outcomes at 1 year. Differences in predictors for mortality might improve risk stratification and management goals. [ABSTRACT FROM AUTHOR]

Aims: To identify differences in clinical epidemiology, in-hospital management and 1-year outcomes among patients hospitalized for acute heart failure (AHF) and enrolled in the European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) Registry, stratified by clinical profile at admission.Methods and Results: The ESC-HF-LT Registry is a prospective, observational study collecting hospitalization and 1-year follow-up data from 6629 AHF patients. Among AHF patients enrolled in the registry, 13.2% presented with pulmonary oedema (PO), 2.9% with cardiogenic shock (CS), 61.1% with decompensated heart failure (DHF), 4.8% with hypertensive heart failure (HT-HF), 3.5% with right heart failure (RHF) and 14.4% with AHF and associated acute coronary syndromes (ACS-HF). The 1-year mortality rate was 28.1% in PO, 54.0% in CS, 27.2% in DHF, 12.8% in HT-HF, 34.0% in RHF and 20.6% in ACS-HF patients. When patients were classified by systolic blood pressure (SBP) at initial presentation, 1-year mortality was 34.8% in patients with SBP <85 mmHg, 29.0% in those with SBP 85-110 mmHg, 21.2% in patients with SBP 110-140 mmHg and 17.4% in those with SBP >140 mmHg. These differences tended to diminish in the months post-discharge, and 1-year mortality for the patients who survived at least 6 months post-discharge did not vary significantly by either clinical profile or SBP classification.Conclusion: Rates of adverse outcomes in AHF remain high, and substantial differences have been found when patients were stratified by clinical profile or SBP. However, patients who survived at least 6 months post-discharge represent a more homogeneous group and their 1-year outcome is less influenced by clinical profile or SBP at admission. [ABSTRACT FROM AUTHOR]

Aims: To identify differences in clinical epidemiology, in-hospital management and 1-year outcomes among patients hospitalized for acute heart failure (AHF) and enrolled in the European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) Registry, stratified by clinical profile at admission. Methods and results: The ESC-HF-LT Registry is a prospective, observational study collecting hospitalization and 1-year follow-up data from 6629 AHF patients. Among AHF patients enrolled in the registry, 13.2% presented with pulmonary oedema (PO), 2.9% with cardiogenic shock (CS), 61.1% with decompensated heart failure (DHF), 4.8% with hypertensive heart failure (HT-HF), 3.5% with right heart failure (RHF) and 14.4% with AHF and associated acute coronary syndromes (ACS-HF). The 1-year mortality rate was 28.1% in PO, 54.0% in CS, 27.2% in DHF, 12.8% in HT-HF, 34.0% in RHF and 20.6% in ACS-HF patients. When patients were classified by systolic blood pressure (SBP) at initial presentation, 1-year mortality was 34.8% in patients with SBP <85 mmHg, 29.0% in those with SBP 85-110 mmHg, 21.2% in patients with SBP 110-140 mmHg and 17.4% in those with SBP >140 mmHg. These differences tended to diminish in the months post-discharge, and 1-year mortality for the patients who survived at least 6 months post-discharge did not vary significantly by either clinical profile or SBP classification. Conclusion Rates of adverse outcomes in AHF remain high, and substantial differences have been found when patients were stratified by clinical profile or SBP. However, patients who survived at least 6 months post-discharge represent a more homogeneous group and their 1-year outcome is less influenced by clinical profile or SBP at admission. [ABSTRACT FROM AUTHOR]

Background New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. Methods We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection. Results During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection. Conclusion Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection. [ABSTRACT FROM AUTHOR]