Search

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus., Competing Interests: Conflict of interest: none declared., (© The Authors 2024. Published by John Wiley & Sons Limited and Oxford University Press on behalf of the European Society of Cardiology, and Frontiers Media SA on behalf of the European Society for Organ Transplantation.)

Aims: Temporal changes in patient selection and major technological developments have occurred in the field of left ventricular assist devices (LVADs), yet analyses depicting this trend are lacking for Europe. We describe the advances of European LVAD programmes from the PCHF-VAD registry across device implantation eras., Methods and Results: Of 583 patients from 13 European centres in the registry, 556 patients (mean age 53 ± 12 years, 82% male) were eligible for this analysis. Patients were divided into eras (E) by date of LVAD implantation: E1 from December 2006 to December 2012 (6 years), E2 from January 2013 to January 2020 (7 years). Patients implanted more recently were older with more comorbidities, but less acutely ill. Receiving an LVAD in E2 was associated with improved 1-year survival in adjusted analysis (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.98; p = 0.043). LVAD implantation in E2 was associated with a significantly lower chance of heart transplantation (adjusted HR 0.40, 95% CI 0.23-0.67; p = 0.001), and lower risk of LVAD-related infections (adjusted HR 0.64, 95% CI 0.43-0.95; p = 0.027), both in unadjusted and adjusted analyses. The adjusted risk of haemocompatibility-related events decreased (HR 0.60, 95% CI 0.39-0.91; p = 0.016), while heart failure-related events increased in E2 (HR 1.67, 95% CI 1.02-2.75; p = 0.043)., Conclusion: In an analysis depicting the evolving landscape of continuous-flow LVAD carriers in Europe over 13 years, a trend towards better survival was seen in recent years, despite older recipients with more comorbidities, potentially attributable to increasing expertise of LVAD centres, improved patient selection and pump technology. However, a smaller chance of undergoing heart transplantation was noted in the second era, underscoring the relevance of improved outcomes on LVAD support., (© 2022 European Society of Cardiology.)

Although the use of induction therapy has reduced the risk of acute rejection after heart transplantation, its use may be associated with other adverse outcomes. We aimed to examine the effect of no induction (NoInd), induction with basiliximab (BAS), or induction with antithymocyte globulin (ATG) on outcome after heart transplantation. We analyzed data from the International Society for Heart and Lung Transplantation (ISHLT) registry for adult heart transplants performed between 2000 and 2013. The primary outcome was cumulative all-cause mortality, and the secondary outcome was cause-specific death. We identified 27 369 transplants whose recipients received NoInd (n = 15 688), ATG (n = 6830), or BAS (n = 4851). Over a median follow-up of 1497 days, overall 30-day mortality was 5% and 1-year mortality was 11%. Survival after transplant was similar in patients treated with NoInd compared with ATG. The survival was improved using NoInd compared with BAS (log-rank P = .040), adjustment HR = 1.11 (95% CI, 1.04-1.19). Compared to NoInd, BAS was associated with higher risk of graft failure-related deaths, HR = 1.27 (95% CI, 1.02-1.58), and ATG was associated with higher risk of malignancy-related deaths, HR = 1.18 (95% CI, 1.01-1.39). Survival of patients who received NoInd was similar to ATG and better compared with BAS. Further, the use of ATG may be associated with increased malignancy-related mortality, compared with NoInd., (© 2020 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: Continuous-flow mechanical circulatory support (CF-MCS) is associated with impaired vascular function and increased risk of vasoplegia. One contributing factor to early graft failure (EGF) is severe vasoplegia. We tested the hypothesis that CF-MCS is associated with increased risk of EGF., Methods: Adult primary heart transplant recipients in the ISHLT Registry from 2005 to 2013 were stratified into three groups based on pre-transplant MCS: No MCS (n = 11 748), pulsatile (P)-MCS (n = 718), and CF-MCS (n = 3818). EGF was defined as death/retransplantation due to graft failure within 30 days after HT. Comparisons were made using descriptive statistics and associations. EGF was assessed with multivariable Cox proportional hazard regression., Results: The incidence of EGF within 30 days was similar between groups (No MCS 2.2%, P-MCS 3.3%, CF-MCS 2.1%, P = .10). Following multivariable adjustment, the risk of EGF was not statistically different for those with CF-MCS compared with P-MCS (HR 0.75, 95% CI 0.46-1.21, P = .24). The risk of EGF was numerically, but not statistically significantly higher for CF-MCS compared with No MCS (HR 1.24, 95% CI 0.92-1.67, P = .16)., Conclusion: CF-MCS use was not associated with a statistically significant increased risk of EGF resulting in death or retransplantation in the first 30 days after transplant., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Recipient age and donor age are well-known prognostic factors in adult heart transplantation. However, the association between donor age and recipient age and their interaction and short- and long-term mortality is unknown., Methods: We studied 64,354 heart transplants to adult recipients between 1988 and 2013 in the ISHLT Registry. Donor age and recipient age were analyzed as continuous and categorical variables and restricted cubic spline functions to assess non-linear associations and interactions. The end-point was all-cause mortality., Results: In the multivariable analysis, the odds ratio for 30-day mortality per 10-year increase in recipient age was 1.05 (95% confidence interval [CI] 1.01 to 1.08, p = 0.009) compared with 1.19 (95% CI 1.15 to 1.22, p < 0.001) for donor age. In the first year, the hazard ratio for mortality was 1.05 (95% CI 1.02 to 1.07, p < 0.001) for a 10-year increase in recipient age and 1.16 (1.14 to 1.18, p < 0.001) for donor age. In Years 1 to 3, 3 to 5, and 5 to 10 post-transplant, the hazard ratio was 0.89 (95% CI 0.86 to 0.92, p < 0.001), 0.98 (95% CI 0.94 to 1.02, p = 0.266), and 1.14 (95% CI 1.11 to 1.17, p < 0.001) for recipient age, and 1.12 (95% CI 1.08 to 1.14, p < 0.001), 1.07 (95% CI 1.03 to 1.10, p < 0.001), and 1.07 (95% CI 1.05 to 1.10, p < 0.001) for donor age, respectively. There was no interaction of recipient age and donor age with survival at any follow-up time-point., Conclusions: At 30 days, both higher donor age and recipient age were associated with higher mortality. At 1 to 10 years, older donor age was associated with higher mortality at all follow-up time-points, but the hazard was greater in the short term, and recipient age was associated only with longer term mortality. The risk from donor age appears equal across recipient age groups., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Rheumatic heart disease (RHD), an autoimmune sequela of Group A streptococcal infection, is a chronic valvular disease affecting 32 million people worldwide, predominantly in developing nations. As the predisposition to autoimmune sequela still remains post transplantation, our primary objective was to assess if there were differences in mortality and rejection rates., Methods and Results: Using the International Society for Heart and Lung Transplantation (ISHLT) adult heart transplant registry, we identified 42 RHD patients who had undergone heart transplantation between 1988 and 2014. We matched the 42 RHD recipients by transplant year, age, and gender to 420 dilated cardiomyopathy (DCM) recipients. One-year mortality in the RHD group was 17.95% vs. 7.92% in the DCM group (P = 0.07). Survival was significantly reduced in the RHD group vs. the DCM group via Kaplan Meier curves (P = 0.04). In a multivariate model, RHD status (OR 3.19, 95% CI 1.15-8.83, P = 0.025) and serum creatinine (OR 1.41, 95% CI 1.09-1.82, P = 0.009) were associated with an increased odds of one-year mortality (P = 0.0013)., Conclusions: At one year post transplantation, RHD recipients had a significantly lower survival than DCM recipients. RHD status was also an independent predictor of mortality at 1 year post transplantation., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Background: Malignancy is a concern in cardiac transplant recipients, but the temporal trends of de novo malignancy development are unknown., Objectives: The goal of this study was to describe the temporal trends of the incidence, types, and predictors of de novo malignancy in cardiac transplant recipients., Methods: The authors analyzed the temporal trends of post-transplant incidence, types, and predictors of malignancy using 17,587 primary adult heart-only transplant recipients from the International Society for Heart and Lung Transplantation registry. The main study outcomes included the incidence of, types of, and time to de novo malignancy., Results: The risk of any de novo solid malignancy between years 1 and 5 after transplantation was 10.7%. The cumulative incidence by malignancy type was: skin cancer (7.0%), non-skin solid cancer (4.0%), and lymphoproliferative disorders (0.9%). There was no temporal difference in the time to development according to malignancy type. However, the cumulative incidence of de novo solid malignancy increased from 2000 to 2005 vs. 2006 to 2011 (10.0% vs. 12.4%; p < 0.0001). Survival in patients after de novo malignancy was markedly lower than in patients without malignancy (p < 0.0001). Older recipients and patients who underwent transplantation in the recent era had a higher risk of de novo malignancy., Conclusions: More than 10% of adult heart transplant recipients developed de novo malignancy between years 1 and 5 after transplantation, and this outcome was associated with increased mortality. The incidence of post-transplant de novo solid malignancy increased temporally, with the largest increase in skin cancer. Individualized immunosuppression strategies and enhanced cancer screening should be studied to determine whether they can reduce the adverse outcomes of post-transplantation malignancy., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Heart transplantation (HTx) and implantable left ventricular assist systems (LVAS) improve outcomes in advanced heart failure but may be underutilized. We hypothesized that screening can identify appropriate candidates., Methods and Results: The ScrEEning for advanced Heart Failure treatment (SEE-HF) study was a multicentre prospective study screening patients with existing cardiac resynchronization therapy (CRT) and/or implantable cardioverter-defibrillator (ICD) for ejection fraction ≤40% and New York Heart Association (NYHA) class III-IV, and subsequently for guideline-based HTx and LVAS indication. Of 1722 (mean age 64 ± 14 years, 26% women) patients screened at eight centres in seven European countries, 121 (7.0%) were eligible and 99 (5.7%; mean age 61 ± 10 years, 19% women) patients were enrolled for detailed assessment. Twenty-six of the 99 enrolled patients (26%) were eligible for either HTx or LVAD (18 eligible for HTx; 7 eligible for LVAD; and 1 eligible for both). Eleven patients were listed for HTx and three received an LVAS. Eligible patients were 61 ± 8 years and 19% women, whereas those actually receiving intervention were 56 ± 8 years and 8% women., Conclusions: Among patients with CRT and/or ICD, a minority have NYHA class III-IV heart failure and ejection fraction ≤40%. Among these, however, more than one-quarter have an unrecognized need for HTx or LVAS. When patients are offered intervention based on screening, many decline. Discrepancies exist between clinical and patient equipoise. Clinical Trial Registration ClinicalTrials.gov Unique Identifier: NCT00894387., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Background: Survival beyond 1 year after heart transplantation has remained without significant improvement for the last 2 decades. A more individualized approach to post-transplant care could result in a reduction of long-term mortality. Although recipient age has been associated with an increased incidence of certain post-transplant morbidities, its effect on cause-specific mortality has not been established., Methods: We analyzed overall and cause-specific mortality of heart transplant recipients registered in the International Society for Heart and Lung Transplantation Registry between 1995 and 2011. Patients were grouped by recipient age: 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥ 70 years. Multivariable regression models were used to examine the association between recipient age and leading causes of post-transplant mortality. We also compared immunosuppression (IS) use among the different recipient age groups., Results: There were 52,995 recipients (78% male; median age [5th, 95th percentile]: 54 [27, 66] years). Survival through 10 years after transplant was lower in heart transplant recipients in the 2 more advanced age groups: 49% for 60 to 69 years and 36% for ≥ 70 years (p < 0.01 for pairwise comparisons with remaining groups). The risk of death caused by acute rejection (hazard ratio [HR], 4.11; p < 0.01), cardiac allograft vasculopathy (HR, 2.85; p < 0.01), and graft failure (HR, 2.29; p < 0.01) was highest in the youngest recipients (18-29 years) compared with the reference group (50-59 years). However, the risk of death caused by infection (HR, 2.10; p < 0.01) and malignancy (HR, 2.23; p < 0.01) was highest in older recipients (≥ 70 years). Similarly, the risk of death caused by renal failure was lower in younger recipients than in the reference group (HR, 0.53; p < 0.01 for 18-49 years vs 50-59 years). The use of induction IS was similar among the different recipient age groups, and differences in maintenance IS were not clinically important., Conclusions: Causes of death in this large cohort of heart transplant recipients varied significantly with recipient age at the time of transplant, with cause-specific mortality profiles suggesting a possible effect of inadequate IS in younger recipients and over-IS in older recipients. Thus, a more personalized approach, possibly including different IS strategies according to recipient age, might result in improved post-transplant survival., (Published by Elsevier Inc.)

Introduction: Numerous cohort analyses suggest rapidly increasing use of mechanical circulatory support (MCS) as a bridge to heart transplantation (HTx), but the role of age in selection for MCS remains unknown., Methods: We assessed adult HTx in the International Society for Heart And Lung Transplantation Registry between 2005 and 2013 and we determined MCS use by recipient age group and transplant year. Multivariable logistic regression models were constructed to identify variables associated with continuous flow (CF) left ventricular assist device (LVAD) use within each age group., Results: Among 16,480 HTx recipients the percentage of overall MCS use increased from 23% to 38%, 21% to 41%, and 17% to 42% in age groups 18-39 years, 40-59 years and over 60 years, respectively. This effect was mainly due to an increase in CF LVAD use and primarily in HTx recipients aged over 60. In multivariable analyses, male gender and blood group O were significantly associated with CF LVAD use in all age groups., Conclusions: Bridge to transplant MCS use increased dramatically between 2005 and 2013 primarily due to increased use of CF LVAD and primarily in higher ages. Pre-HTx CF LVAD use was more frequent in men and blood group O., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Heart failure (HF) is associated with pathological activation of arginine vasopressin, measured in plasma by the pre-hormone fragment copeptin. We hypothesised that copeptin is elevated and associated with worse prognosis in HF, and that left ventricular assist device (LVAD) therapy and heart transplantation (HTx) are associated with lower levels of copeptin., Methods: We measured copeptin in groups of 49 patients with advanced HF, 13 patients one year post-LVAD and 22 patients one year post-HTx and correlated with clinical data and cardiac output. In HF we also assessed the prognostic role of copeptin with Kaplan-Meier analysis and multivariate Cox regression., Results: In HF, median (interquartile range) copeptin was 28 (18-45) pmol/L, after LVAD 16 (6-27) pmol/L, and after HTx 12 (5-20) pmol/L (p overall <0.001). In HF, copeptin was an independent predictor of death, LVAD or HTx (hazard ratio for log copeptin, 3.28 [95% confidence interval: 1.66-6.50], p=0.001)., Conclusions: Copeptin was elevated in, and independently predicted prognosis in, HF. Copeptin was progressively lower after LVAD and HTx. This suggests that improvement in cardiac output with LVAD and HTx may induce progressively reduced activation of vasopressin, which may be a marker for the beneficial effects of LVAD and HTx., (Copyright © 2016. Published by Elsevier B.V.)

Background: Pre-transplant amiodarone use has been postulated as a risk factor for morbidity and mortality after orthotopic heart transplantation (OHT). We assessed pre-OHT amiodarone use and tested the hypothesis that it is associated with impaired post-OHT outcomes., Methods: We performed a retrospective cohort analysis of adult OHT recipients from the registry of the International Society for Heart and Lung Transplantation (ISHLT). All patients had been transplanted between 2005 and 2013 and were stratified by pre-OHT amiodarone use. We derived propensity scores using logistic regression with amiodarone use as the dependent variable, and assessed the associations between amiodarone use and outcomes with Kaplan-Meier analysis after matching patients 1:1 based on propensity score, and with Cox regression with adjustment for propensity score., Results: Of the 14,944 OHT patients in the study cohort, 32% (N = 4,752) received pre-OHT amiodarone. Amiodarone use was higher in recent years (29% in 2005 to 2007, 32% in 2008 to 2010, 35% in 2011 to 2013). Amiodarone-treated patients were older and more frequently had a history of sudden cardiac death (27% vs 13%) and pre-OHT mechanical circulatory support. Key donor characteristics and allograft ischemia times were similar between groups. In propensity-matched analyses, amiodarone-treated patients had higher rates of cardiac reoperation (15% vs 13%) and permanent pacemaker (5% vs 3%) after OHT and before discharge. Amiodarone-treated patients also had higher 1-year mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30), but the risks of early graft failure, retransplantation and rehospitalization were similar between groups., Conclusions: Amiodarone use before OHT was independently associated with increased 1-year mortality. The need for amiodarone therapy should be carefully and continuously assessed in patients awaiting OHT., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Heart transplantation (HT) recipients may have tachycardia secondary to cardiac denervation. As higher heart rate predicts worse outcomes in cardiovascular disease, we hypothesized that tachycardia and nonuse of β blockers are associated with increased mortality after HT. All patients who underwent HT at our institution from 1987 to 2010 were included. The association of heart rate 3 months after HT and β-blocker use during follow-up to mortality was assessed using Kaplan-Meier and multivariate Cox proportional hazards regression analyses adjusting for clinically relevant baseline variables. From 1987 to 2010, there were 493 HT. After excluding 29 who died within 3 months and 3 with follow-up <3 months, 461 HT recipients (50 ± 2 years; 20% women) were included. Over a follow-up of 12 ± 7 years, selected important univariate predictors of post-HT mortality were older age, male gender, higher body mass index, ischemic cardiomyopathy, longer post-HT intensive care unit stay, and hospitalization and at 3 months, increased mean pulmonary artery pressure, right atrial pressure and pulmonary capillary occlusion pressure, higher heart rate, and nonuse of β blockers during follow-up. In multivariate analysis, older ager, longer hospitalization, higher mean pulmonary artery pressure, higher heart rate at 3 months (hazard ratio 1.02 per beat, 95% confidence interval 1.008 to 1.035, p = 0.02) and nonuse of β blockers (hazard ratio 1.43, 95% confidence interval 1.002 to 2.031, p <0.05) were associated with mortality. In conclusion, in a large single-center cohort of HT recipients, higher heart rate and nonuse of β blockers were independently associated with higher mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The use of induction therapy may reduce the risk of acute rejection after heart transplantation. This study assessed the association between basiliximab (BAS) vs anti-thymocyte globulin (ATG) induction and long-term survival after heart transplantation., Methods: We used data from the International Society for Heart and Lung Transplantation Registry to examine outcomes of all adult heart transplant recipients treated with ATG or BAS as induction therapy., Results: We identified 9,324 transplantations performed between 2000 and 2011 whose recipients received ATG (n = 6,144) or BAS (n = 3,180). The ATG group had a higher panel reactive antibody class 1 (7.5% vs 6.1%; p < 0.018) and class 2 (6.6% vs 3.7%; p < 0.001), respectively, whereas the BAS group was less likely to have non-ischemic cardiomyopathy but more likely to be in the intensive care unit pre-transplant. One-year survival was similar for both groups, 90% vs 91% (p = 0.858). However, use of BAS was associated with poorer long-term survival compared with ATG at 5 years (77% vs 82%, p = 0.005) and at 10 years (64% vs 67%, p = 0.007). In multivariable Cox model, use of BAS remained associated with increased mortality over a median follow-up of 3.0 years (range, 0-12 years), with a hazard ratio of 1.22 (95% confidence interval, 1.09-1.37; p < 0.001). Sub-group analyses showed BAS was not independently associated with increased risk in those who received a previous transplant or in those who underwent re-transplantation due to graft failure., Conclusions: In the International Society for Heart and Lung Transplantation Registry experience, use of ATG rather than BAS as induction therapy appears to be associated with better long-term survival. A prospective study is necessary to confirm these findings., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: Ghrelin is an anabolic hormone that is elevated in heart failure (HF), with resistance to its anabolic effects. This resolves after heart transplantation (HTx). Ghrelin exists in acylated and des-acyl forms, with the acylated form being primarily responsible for endocrine actions. We tested the hypothesis that ghrelin derangements in HF are due to inadequate acylation and that this resolves post transplantation., Design: Plasma levels of des-acyl and acylated ghrelin and acylated/total ratios were assessed in HF (n = 20), post-HTx (n = 35), and healthy controls (n = 4), and correlated with each other and with clinical parameters., Results: Median (interquartile range) of des-acyl ghrelin level, was 167 (121-195) pg/ml in HF versus 149 (130-223) pg/ml in post-HTx, p = NS. Acylated ghrelin level was 76 (51-99) pg/ml versus 13 (0-30) pg/ml, p < 0.001. Acylated/total ratios were 0.33 (0.20-0.47) versus 0.08 (0-0.13), p < 0.001. The correlation between acylated and total ghrelin levels was greater in HF than that in HTx. Acyl ghrelin correlated inversely with body mass index in HF, but not in HTx., Conclusion: Acylated ghrelin and the acylated/total ratio were dramatically higher in HF compared with those in HTx. Acylation rather than secretion of ghrelin is upregulated in HF and the resistance to ghrelin's anabolic and appetite-stimulating effects is not at the level of acylation, but downstream at the ghrelin-receptor level.

Background: The Seattle Heart Failure Model (SHFM) predicts survival in heart failure but may underestimate risk in severe heart failure, and the performance has not been evaluated explicitly in patients with cardiac resynchronization therapy (CRT) and/or implantable cardioverter defibrillator (ICD) referred for heart transplantation. We aimed to assess the utility of the SHFM by validation in patients with CRT and/or ICD referred for heart transplantation., Methods: We assessed the SHFM performance in 382 patients with CRT and/or ICD referred for heart transplantation. Outcome was survival free from urgent transplantation or left ventricular assist device. Model discrimination and calibration were assessed graphically and by formal tests., Results: During a mean follow-up of 2.3 years, 195 events occurred. One-, 2-, and 3-year observed event-free survival was 77%, 62%, and 52%, and the observed to predicted event-free survival ratio was 0.89, 0.80, and 0.76. Calibration plots demonstrated results deviating from the ideal calibration line at 1, 2, and 3 years. The SHFM score adequately assigned patients in discrete risk strata, according to Kaplan-Meier estimated survival. Time-dependent receiver operating characteristic curve analyses demonstrated good discrimination overall, which was slightly better for 1-year (area under the curve [AUC] 0.774) compared with 2-year (AUC 0.742) and 3-year (AUC 0.728) event-free survival., Conclusions: The SHFM has good discrimination but underestimates risk of adverse outcomes in patients with CRT and/or ICD referred for heart transplantation. The SHFM may be used to assess relative risk and changes over time, but when assessing absolute percentage of event-free survival, the overestimation of event-free survival should be accounted for., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: The Heart Failure Survival Score (HFSS) risk-stratifies patients with chronic heart failure (CHF) referred for heart transplantation using 7 parameters, including peak VO₂. The Seattle Heart Failure Model (SHFM) is a 20-variable model that combines clinical, laboratory and therapeutic data. Although both models have excellent accuracy, only the HFSS was derived and validated in patients referred for transplantation, and the HFSS and SHFM have not been directly compared., Methods: We tested the accuracy of the SHFM and compared the HFSS and SHFM in 715 patients referred for heart transplantation., Results: Over a follow-up of 962 ± 912 days, 354 patients died or received an urgent heart transplantation or a ventricular assist device. One-year event-free survival was 89%, 72% and 60%, respectively, for the low-, medium- and high-risk HFSS strata, and 93%, 76%, and 58%, respectively, for the low-, medium- and high-risk SHFM strata. The HFSS and SHFM were modestly correlated (R = -0.48, p < 0.001). In receiver operating characteristic curve analysis, areas under the curves (AUCs) for the HFSS and SHFM were comparable (1 year: 0.72 vs 0.73; 2-year: 0.70 vs 0.74, respectively) and incremental to New York Heart Association class. The 1- and 2-year combined HFSS+SHFM AUCs were 0.77 and 0.76, respectively, significantly better than the HFSS or SHFM alone., Conclusions: The HFSS and SHFM provide accurate and comparable risk stratification in CHF patients referred for transplantation. Combining the HFSS and SHFM improves predictive ability., (2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The peak oxygen consumption (VO(2)) and the Heart Failure Survival Score (HFSS) risk stratify patients with chronic heart failure (CHF) referred for heart transplantation. However, these tools were developed before widespread use of implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT). The prognostic accuracy of these tools in patients with ICD and/or CRT is unknown., Methods: Cardiopulmonary exercise testing with measurement of peak VO(2) and calculation of the HFSS was done in 715 CHF patients (54 ± 12 years; ICD, 244; CRT, 30; CRT-D, 108; none, 333) referred for heart transplantation., Results: During an average follow-up of 962 ± 912 days, 354 patients died or received urgent heart transplant or left ventricular assist device. By Cox hazard analysis, both peak VO(2) and HFSS were powerful independent prognostic markers. By Kaplan-Meier analysis, the HFSS was effective in discriminating patients into low-, medium-, and high-risk groups in all device groups. In contrast, the peak VO(2) did not discriminate between low (>14 ml/min/kg) and medium (10.1 to 14 ml/min/kg) risk in device patients. By area under the receiver operating characteristic curve, the HFSS performed better than the peak VO(2) (1-year in total cohort; 0.72 vs. 0.65; p < 0.001; 1-year in device patients; 0.69 vs. 0.65; p < 0.001)., Conclusion: The HFSS outperforms the peak VO(2) in risk stratification for CHF in the presence of an ICD and/or CRT. Furthermore, a peak VO(2) ≤ 10 ml/kg/min rather than the traditional cutoff value ≤ 14 ml/min/kg may be more useful for risk stratification in the device era., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The aim of the present study was to determine whether peak oxygen consumption (VO(2)) and the Heart Failure Survival Score (HFSS) predict prognosis in European-American, African-American, and Hispanic-American patients with chronic heart failure referred for heart transplantation. The peak VO(2) and the HFSS have previously been shown to effectively risk stratify patients with chronic heart failure and are criteria for the listing for heart transplantation. However, the effect of race on the predictive value of these variables has not been studied. A total of 715 patients with congestive heart failure (433 European American, 126 African American, 123 Hispanic American, and 33 other), who had been referred for heart transplantation, underwent cardiopulmonary exercise testing with measurement of the peak VO(2) and calculation of the HFSS. A total of 354 patients had died or undergone urgent heart transplantation or implantation of a left ventricular assist device during the 962 +/- 912 days of follow-up. On univariate and multivariate Cox hazard analysis, both peak VO(2) and the HFSS were powerful prognostic markers in the overall cohort and in the separate races. In the receiver operating characteristic curve analysis, the areas under the curve at 1 and 2 years of follow-up were greater for the HFSS than for peak VO(2). In conclusion, HFSS and peak VO(2) can be used for transplant selection; however, in the era of modern therapy and across races and genders, the HFSS might perform better than the peak VO(2)., (Copyright 2010 Elsevier Inc. All rights reserved.)

Extracorporeal membrane oxygenation (ECMO) systems have undergone rapid technological improvements and are now feasible options for medium-term support of severe cardiac or pulmonary failure. Intractable ventricular arrhythmia is a rare but well-established indication for heart transplantation. We report a case of persistent ventricular fibrillation (VF) that was rescued by insertion of peripheral veno-arterial ECMO during cardiopulmonary resuscitation, which provided support for 30 h of continuous VF and subsequently permitted urgent heart transplantation.

Aims: Severe heart failure (HF) is often associated with cachexia that reverses post-heart transplantation (HTx) with frequent development of obesity. Ghrelin is a novel appetite-stimulating hormone. The aim was to determine the role of ghrelin in regulating appetite, food intake, and body composition in HF and post-HTx., Methods and Results: We measured serial ghrelin, hunger sensation, caloric intake, and body composition in 12 HF patients awaiting HTx, 12 patients 12.7 +/- 8.6 months post-HTx, and 7 controls. Seven of 12 HF patients were followed for longitudinal analysis post-HTx. Body mass index was 23.1 +/- 3.1 in HF and 31.5 +/- 5.5 post-HTx (P < 0.001). Heart transplantation patients had gained 18.0 +/- 7.7 kg since HTx. Ghrelin area under the curve between controlled meals (control: 186 +/- 39; HF: 264 +/- 71; HTx: 194 +/- 47 ng min/mL, P < 0.007) was higher in HF, but test meal caloric intake (control: 1185 +/- 650; HF: 391 +/- 103; HTx: 831 +/- 309 kcal, P < 0.008) was lower in HF. The longitudinal analysis confirmed these findings., Conclusion: Heart failure may be associated with resistance to the appetite-stimulating effects of ghrelin, which may contribute to cachexia. Heart transplantation may be associated with resolution of ghrelin resistance, which may contribute to weight gain. These findings are preliminary and should be confirmed in larger trials.

Aims: Severe heart failure (HF) is associated with cachexia; this is often reversed post cardiac transplantation (HTx) with frequent development of obesity. Growth hormone (GH) resistance is common in HF and may contribute to cachexia. Whether GH resistance resolves post HTx is unknown. We aimed to confirm that HF is associated with GH resistance and to test the hypothesis that GH resistance resolves post HTx., Methods and Results: We measured GH, insulin-like growth factor-1 (IGF-1), and body composition in 10 HF patients awaiting HTx, in 18 patients 11 +/- 8 months post HTx, and seven controls. Body mass index was 23.5 +/- 3.2 in HF patients and 29.3 +/- 5.7 post HTx. HTx patients had gained 14 +/- 8 kg since HTx. GH was elevated in HF (control: 0.21 +/- 0.25; HF: 1.13 +/- 1.19; HTx: 0.11 +/- 0.13 ng/mL; P < 0.007), while IGF-1 was higher in HTx (control: 114 +/- 57; HF: 94 +/- 52; HTx: 190 +/- 106 ng/mL; P < 0.02). HTx had higher total body and abdominal fat %., Conclusion: GH resistance is present in severe HF and resolves post HTx. These findings should be confirmed through larger trials.

Background: Substantial weight gain frequently occurs after cardiac transplant (CT) and increases the risk of secondary disease. It is unclear, however, if weight gain after CT is related to glucocorticoid immunosuppressive therapy., Methods: A retrospective chart review was performed on the first 200 patients undergoing CT and the first 200 patients undergoing renal transplant (RT) at Columbia Presbyterian Medical Center, starting in January 2000. Patients who survived 1 year and had their weight recorded at transplant were included in the study. Rejection episodes and prednisone treatment was recorded for CT patients. Regression analysis was used to determine predictors of weight gain., Results: A total of 158 CT patients and 128 RT patients were included in the data analysis. The weight of CT patients at time of transplant was (mean +/- SD) 76.3 +/- 14.6 kg and increased by 10.3 +/- 10.6 kg (p < 0.05) by 1-year post-transplant. Pre-transplant weight of the RT patients was 74.1 +/- 20.1 kg; by 1-year post-RT, weight increased by 3.5 +/- 8.6 kg (p < 0.05). The weight gain in CT patients was significantly greater than in the RT patients (p < 0.001). Post-transplant weight change in multiple regression models was related to age, gender (male) and transplant type (cardiac), but not to prednisone dose or pre-transplant weight., Conclusions: CT results in substantial post-surgical weight gain, which is greater than that observed for RT. Overweight and obesity development was not related to prednisone dose alone. This observation may have important clinical and research implications.

Aims: Patients with advanced heart failure (AdHF) who are ineligible for heart transplantation (HTx) can become candidates for treatment with a left ventricular assist device (LVAD) in some countries, but not others. This reflects the lack of a systematic analysis of the usefulness of LVAD systems in this context, and of their benefits, limitations and cost-effectiveness. The SWEdish evaluation of left Ventricular Assist Device (SweVAD) study is a Phase IV, prospective, 1:1 randomized, non-blinded, multicentre trial that will examine the impact of assignment to mechanical circulatory support with guideline-directed LVAD destination therapy (GD-LVAD-DT) using the HeartMate 3 (HM3) continuous flow pump vs. guideline-directed medical therapy (GDMT) on survival in a population of AdHF patients ineligible for HTx.Methods: A total of 80 patients will be recruited to SweVAD at the seven university hospitals in Sweden. The study population will comprise patients with AdHF (New York Heart Association class IIIB-IV, INTERMACS profile 2-6) who display signs of poor prognosis despite GDMT and who are not considered eligible for HTx. Participants will be followed for 2 years or until death occurs. Other endpoints will be determined by blinded adjudication. Patients who remain on study-assigned interventions beyond 2 years will be asked to continue follow-up for outcomes and adverse events for up to 5 years.Conclusion: The SweVAD study will compare survival, medium-term benefits, costs and potential hazards between GD-LVAD-DT and GDMT and will provide a valuable reference point to guide destination therapy strategies for patients with AdHF ineligible for HTx. [ABSTRACT FROM AUTHOR]

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies. [ABSTRACT FROM AUTHOR]

Refractory cardiogenic shock (RCS) is associated with a high mortality. Veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) is increasingly used as acute cardiopulmonary support but selection of VA‐ECMO candidates remains challenging. There are limited data on which pre‐VA‐ECMO variables that predict outcome. The aim of this study was to identify pre‐VA‐ECMO predictors of 90‐day mortality. We retrospectively analyzed 76 consecutive patients (median age 52; interquartile range [IQR]: 37–60) supported with VA‐ECMO due to RCS. The association between pre‐implant variables and all‐cause mortality at 90 days was analyzed with multivariable logistic regression. Main etiologies of RCS were acute myocardial infarction 51% and other AHF etiologies 49%. Cardiopulmonary resuscitation was performed in 54% of patients before initiation of VA‐ECMO. Median duration of VA‐ECMO was 5 days (IQR: 2–11). The 90‐day overall mortality was 49% and in‐hospital mortality was 50%; 46% died on VA‐ECMO, 37% were successfully weaned, 13% were bridged to heart transplantation, and 4% to left ventricular assist device. Multivariable logistic regression analysis identified arterial lactate (odds ratio [OR] per mmol/L: 1.15; 95% confidence interval [CI]: 1.06–1.24; P = 0.001) and number of inotropes and vasopressors (OR per agent: 2.14; 95% CI: 1.26–3.63; P = 0.005) as independent predictors of 90‐day mortality. In RCS patients arterial lactate level and number of inotropes and vasopressors were identified as independent pre‐VA‐ECMO predictors of 90‐day mortality. Thus, the severity of cardiogenic shock expressed as levels of lactate and vasoactive agents just before start of VA‐ECMO may be more predictive of outcome than the specific etiology of cardiogenic shock. [ABSTRACT FROM AUTHOR]

Objectives: Soluble suppression of tumorigenecity 2 (sST2) is prognostic in acute and chronic heart failure with reduced ejection fraction (HFrEF) but less studied in HF with preserved EF (HFpEF). We evaluated sST2 concentrations, correlations with biomarkers and echocardiographic measures of diastolic and systolic function, and associations with outcomes in HFpEF and HFrEF.Design and Results: A total of 193 subjects from three different cohorts were included. Eighty-six HFpEF patients were obtained from the Karolinska Rennes (KaRen) study, 86 patients with HFrEF were recruited from referrals to Karolinska University Hospital for advanced assessment of HF, and 21 controls were included (ClinicalTrials.gov Identifier for KaRen: NCT01091467). HFrEF and controls cohorts did not have ClinicalTrials.gov registrations. sST2 was lower in HFpEF, median (interquartile range); 23 (17-31) compared to HFrEF; 35 (23-52) µg/L, p < .001. In both HFpEF and HFrEF, sST2 correlated positively with NT-proBNP (HFpEF rs=0.392, p < .001 and HFrEF rs=0.466, p < .001). In HFpEF, sST2 correlated to left atrial volume index (rs=0.276, p = .019) but not to E/E´, nor to left ventricular mass index. sST2 was in HFpEF associated with the composite endpoint of death or HF hospitalization, adjusted hazard ratio (HR) per log increase in sST2 6.62, 95% confidence interval (CI) 1.04-42.28, p = .046, and in HFrEF death, heart transplant or left ventricular assist systems; 3.51, 95% CI 1.05-11.69, p = .041.Conclusions: In patients with HFpEF compared to HFrEF, crude levels of sST2 were lower but potentially more strongly associated with outcomes. The lower levels of sST2 in HFpEF than in HFrEF may reflect lower degrees of fibrosis, but the potentially stronger association with outcomes may reflect a greater prognostic importance of progressive fibrosis and as such a greater potential for intervention. In conclusion; this study adds to the evidence of sST2 as prognostic marker in both HFpEF and HFrEF. [ABSTRACT FROM AUTHOR]

Aims: The diastolic pulmonary pressure gradient (DPG) has recently been introduced as a specific marker of combined pre-capillary pulmonary hypertension (Cpc-PH) in left heart disease (LHD). However, its diagnostic and prognostic superiority compared with traditional haemodynamic indices has been challenged lately. Current recommendations explicitly denote that in the normal heart, DPG values are greater than zero, with DPG ≥7 mmHg indicating Cpc-PH. However, clinicians are perplexed by the frequent observation of DPG <0 mmHg (DPGNEG ), as its physiological explanation and clinical impact are unclear to date. We hypothesized that large V-waves in the pulmonary artery wedge pressure (PAWP) curve yielding asymmetric pressure transmission might account for DPGNEG and undertook this study to clarify the physiological and prognostic implications of DPGNEG .Methods and Results: Right heart catheterization and echocardiography were performed in 316 patients with LHD due to primary myocardial dysfunction or valvular disease. A total of 256 patients had PH-LHD, of whom 48% demonstrated DPGNEG . The V-wave amplitude inversely correlated with DPG (r = -0.45, P < 0.001) in patients with low pulmonary vascular resistance (PVR), but not in those with elevated PVR (P > 0.05). Patients with large V-waves had negative and lower DPG than those without augmented V-waves (P < 0.001) despite similar PVR (P >0.05). Positive, but normal DPG (0-6 mmHg) carried a worse 2-year prognosis for death and/or heart transplantation than DPGNEG (hazard ratio 2.97; P < 0.05).Conclusion: Our results advocate against DPGNEG constituting a measurement error. We propose that DPGNEG can partially be ascribed to large V-waves and carries a better prognosis than DPG within the normal positive range. [ABSTRACT FROM AUTHOR]

Heart transplantation (HTx) improves symptoms and prolongs life in advanced heart failure (HF), but organ supply is limited. In recent years, mechanical circulatory support and specifically implantable left ventricular assist devices (LVADs) have undergone technical improvements, and outcomes have improved dramatically. Left ventricular assist devices are now viable options for patients with severe HF as bridge to transplantation, destination therapy, or as bridge to recovery. Many believe that LVADs may soon provide outcomes similar to, or better than, HTx, launching a new era of end-stage HF management. The key to improving outcomes is patient selection, but the field is changing rapidly and guidelines and consensus are limited. This review summarizes recent reports of predictors of poor outcomes and provides an overview of selection for LVAD therapy. [ABSTRACT FROM PUBLISHER]

Extracorporeal membrane oxygenation (ECMO) systems have undergone rapid technological improvements and are now feasible options for medium-term support of severe cardiac or pulmonary failure. Intractable ventricular arrhythmia is a rare but well-established indication for heart transplantation. We report a case of persistent ventricular fibrillation (VF) that was rescued by insertion of peripheral veno-arterial ECMO during cardiopulmonary resuscitation, which provided support for 30 h of continuous VF and subsequently permitted urgent heart transplantation. [ABSTRACT FROM PUBLISHER]

Peak exercise oxygen consumption (Vo 2) and the Heart Failure (HF) Survival Score (HFSS) were developed in middle-aged patient cohorts referred for heart transplantation with HF. The prognostic value of Vo 2 in patients >65 years has not been well studied. Accordingly, the prognostic value of peak Vo 2 was evaluated in these patients with HF. A retrospective analysis of 396 patients with HF >65 years with cardiopulmonary exercise testing was performed. Peak Vo 2 and components of the HFSS (presence of coronary artery disease, left ventricular ejection fraction, heart rate, mean arterial blood pressure, presence of intraventricular conduction defects, and serum sodium) were collected. Follow-up averaged 1,038 ± 983 days. Outcome events were defined as death, implantation of a left ventricular assist device, or urgent transplantation. Patients were divided into risk strata for peak Vo 2 and HFSS based on previous cut-off points. Survival curves were derived using Kaplan-Meier analysis and compared using log-rank analysis. Survival differed markedly by Vo 2 stratum (p <0.0001), with significantly better survival rates for the low- (>14 ml/kg/min) versus medium- (10 to 14 ml/kg/min), low- versus high- (<10 ml/kg/min), and medium- versus high-risk strata (all p <0.05). Survival also differed markedly by HFSS stratum (p <0.0001), with significantly better survival rates for the low- (≥8.10) versus medium- (7.20 to 8.09), low- versus high- (≤7.19), and medium- versus high-risk strata (all p <0.0001). In conclusion, peak Vo 2 and the HFSS were both excellent parameters to predict survival in patients >65 years with HF. [Copyright &y& Elsevier]

Peak VO2 and the Heart Failure Survival Score are 2 clinical parameters used to risk stratify patients with heart failure and time listing for cardiac transplantation. The efficacy of these prognostic variables in patients receiving β-blocker therapy was evaluated. [Copyright &y& Elsevier]