Adherence to 2020 ESC recommendations on physical activity in a population with different cardiovascular risk levels: A prospective population-based study from the CoLaus/PsyCoLaus study.

Introduction: In 2020, the European Society of Cardiology (ESC) recommends 150 min of moderate or 75 min of vigorous-intensity PA per week. While general population PA adherence is suboptimal, its status among those with previous ASCVD or high ASCVD risk remains unknown. We aimed to assess objective adherence to ESC PA recommendations using accelerometer-based measurement among these populations. Methodology: We used data from the Swiss CoLaus|PsyCoLaus cohort study (2014-2016). PA was measured using a 14-day wrist accelerometer. Adherence was defined as > 80 % of recommended PA achievement. Adherence was investigated separately among participants with previous ASCVD and among cardiovascular risk groups (based on the Systematic Coronary Risk Evaluation SCORE-1 and more recent SCORE2) with simple and multivariable logistic regressions. Participants' characteristics were also evaluated as independent factors after adjustment. Results: We studied 1867 participants (median age: 61.2 years, 51.3 % female). ESC PA Adherence reached 55.5 % overall, and 37 % in those with previous ASCVD. Multivariable analysis showed no significant association between previous ASCVD or high cardiovascular risk and PA adherence (Odds ratio adjusted [ORa] 0.9, 95 % Confidence Interval [CI] 0.6-1.4 and ORa 0.7, 95 % CI 0.4-1.2, respectively). Age (≥60 years old), obesity, smoking, chronic renal disease, hypertension, diabetes and benzodiazepine use were significantly associated with lower likelihood of PA adherence in multivariable logistic regression. Conclusion: Adherence to ESC PA guidelines, particularly in participants with higher cardiovascular risk, was poor. Since PA adherence was associated with modifiable risk factors (e.g., obesity, smoking, and benzodiazepine use), maintained efforts to implement the ESC recommendations are advised.

Comparison of HTK-Custodiol and St thomas solution as cardiac preservation solutions on early and midterm outcomes following heart transplantation.

OBJECTIVES: The choice of the cardiac preservation solution for myocardial protection at time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm heart transplantation outcomes. We retrospectively compared our adult heart transplantations performed with two different solutions, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. METHODS: From January 2009 to December 2020, 154 consecutive heart transplantations of adult patients, followed up in pre- and post-transplantation by two different tertiary centers, were performed at the University Hospital of Lausanne, Switzerland. From 2009 to 2015, the cardiac preservation solution used was exclusively St-Thomas, whereafter an institutional decision was made to use HTK-Custodiol only. Patients were classified in two groups accordingly. RESULTS: There were 75 patients in the St-Thomas group and 79 patients in the HTK-Custodiol group. The two groups were comparable in terms of preoperative and intraoperative characteristics. Postoperatively, compared to St-Thomas group, the Custodiol group patients showed significantly lower inotropic scores [median (interquartile range): 35.7 (17.5-60.2) vs 71.8 (31.8-127), p < 0.001], rejection scores [0.08 (0.0-0.25) vs 0.14 (0.05-0.5), p = 0.036] and 30-day mortality rate (2.5% vs 14.7%, p = 0.007) even after adjusting for potential confounders. Microscopic analysis of the endomyocardial biopsies also showed less specific histological features of subendothelial ischaemia (3.8% vs 17.3%, p = 0.006). There was no difference in primary graft dysfunction requiring postoperative extracorporeal membrane oxygenation. The use of HTK-Custodiol solution significantly improved midterm survival (Custodiol vs St-Thomas: HR = 0.20, 95% CI: 0.069 -0.60, p = 0.004). CONCLUSIONS: This retrospective study comparing St-Thomas solution and HTK-Custodiol as myocardial protection during heart procurement showed that Custodiol improves outcomes after heart transplantation, including postoperative inotropic score, rejection score, 30-day mortality and midterm survival.

[New perspectives in the diagnosis and treatment of heart failure with preserved ejection fraction (HFpEF)]. / Avancées dans le diagnostic et traitement de l'insuffisance cardiaque à fraction d'éjection préservée.

Heart failure with preserved ejection fraction (HFpEF), defined as ≥50 %, affects 1 to 3 % of the population and represents a diagnostic challenge. Clinical scores have been developed to facilitate the diagnosis of affected patients, who can now benefit from new treatments. Recent studies have shown a reduction in cardiovascular morbidity and mortality with sodium-glucose cotransporter-2 (SGLT-2) inhibitors in this population. Other promising drugs, currently in the study phase, could potentially change the management approach in the near future. Finally, controlling symptoms, signs of congestion and the frequently encountered comorbidities in this population remain crucial.

L'insuffisance cardiaque à fraction d'éjection préservée (HFpEF), soit ≥ 50 %, touche 1 à 3 % de la population et représente un défi diagnostique. Des scores cliniques ont été développés pour faciliter l'identification des patients concernés qui peuvent désormais bénéficier de nouveaux traitements. Des études récentes ont en effet montré une diminution de la morbimortalité cardiovasculaire grâce aux inhibiteurs du cotransporteur sodium-glucose de type 2 (iSGLT2) dans cette population. D'autres médicaments prometteurs actuellement en phase d'étude pourraient aussi changer la prise en charge dans un futur proche. Enfin, le contrôle des symptômes et signes de congestion ainsi que le traitement des comorbidités fréquemment rencontrées dans cette population restent essentiels.

Primary prophylaxis with mTOR inhibitor enhances T cell effector function and prevents heart transplant rejection during talimogene laherparepvec therapy of squamous cell carcinoma.

The application of mammalian target of rapamycin inhibition (mTORi) as primary prophylactic therapy to optimize T cell effector function while preserving allograft tolerance remains challenging. Here, we present a comprehensive two-step therapeutic approach in a male patient with metastatic cutaneous squamous cell carcinoma and heart transplantation followed with concomitant longitudinal analysis of systemic immunologic changes. In the first step, calcineurin inhibitor/ mycophenolic acid is replaced by the mTORi everolimus to achieve an improved effector T cell status with increased cytotoxic activity (perforin, granzyme), enhanced proliferation (Ki67) and upregulated activation markers (CD38, CD69). In the second step, talimogene laherparepvec (T-VEC) injection further enhances effector function by switching CD4 and CD8 cells from central memory to effector memory profiles, enhancing Th1 responses, and boosting cytotoxic and proliferative activities. In addition, cytokine release (IL-6, IL-18, sCD25, CCL-2, CCL-4) is enhanced and the frequency of circulating regulatory T cells is increased. Notably, no histologic signs of allograft rejection are observed in consecutive end-myocardial biopsies. These findings provide valuable insights into the dynamics of T cell activation and differentiation and suggest that timely initiation of mTORi-based primary prophylaxis may provide a dual benefit of revitalizing T cell function while maintaining allograft tolerance.

European Society of Cardiology guidelines and 1 year outcomes of acute heart failure treatment in Central Asia and Europe.

AIMS: Outcomes reported for patients with hospitalization for acute heart failure (AHF) treatment vary worldwide. Ethnicity-associated characteristics may explain this observation. This observational study compares characteristics and 1-year outcomes of Kyrgyz and Swiss AHF patients against the background of European Society of Cardiology guidelines-based cardiovascular care established in both countries. METHODS AND RESULTS: The primary endpoint was 1 year all-cause mortality (ACM); the secondary endpoint was 1 year ACM or HF-related rehospitalization. A total of 538 Kyrgyz and 537 Swiss AHF patients were included. Kyrgyz patients were younger (64.0 vs. 83.0 years, P < 0.001); ischaemic or rheumatic heart disease and chronic obstructive pulmonary disease were more prevalent (always P < 0.001). In Swiss patients, smoking, dyslipidaemia, hypertension, and atrial flutter/fibrillation were more frequent (always P ≤ 0.035); moreover, left ventricular ejection fraction (LVEF) was higher (47% vs. 36%; P < 0.001), and >mild aortic stenosis was more prevalent (P < 0.001). Other valvular pathologies were more prevalent in Kyrgyz patients (P < 0.001). At discharge, more Swiss patients were on vasodilatory treatment (P < 0.006), while mineralocorticoid receptor antagonists (P = 0.001), beta-blockers (P = 0.001), or loop diuretics (P < 0.001) were less often prescribed. In Kyrgyz patients, unadjusted odds for the primary and secondary endpoints were lower [odds ratio (OR) 0.68, 95% confidence interval (CI): 0.51-0.90, P = 0.008; OR 0.72, 95% CI: 0.56-0.91, P = 0.006, respectively]. After adjustment for age and LVEF, no difference remained (primary endpoint: OR 1.03, 95% CI: 0.71-1.49, P = 0.894; secondary endpoint: OR 0.82, 95% CI: 0.60-1.12, P = 0.206). CONCLUSIONS: On the background of identical guidelines, age- and LVEF-adjusted outcomes were not different between Central Asian and Western European AHF patients despite of large ethnical disparity.

Systematic Estimation of Treatment Effect on Hospitalization Risk as a Drug Repurposing Screening Method.

Drug repurposing (DR) intends to identify new uses for approved medications outside their original indication. Computational methods for finding DR candidates usually rely on prior biological and chemical information on a specific drug or target but rarely utilize real-world observations. In this work, we propose a simple and effective systematic screening approach to measure medication impact on hospitalization risk based on large-scale observational data. We use common classification systems to group drugs and diseases into broader functional categories and test for non-zero effects in each drug-disease category pair. Treatment effects on the hospitalization risk of an individual disease are obtained by combining widely used methods for causal inference and time-to-event modelling. 6468 drug-disease pairs were tested using data from the UK Biobank, focusing on cardiovascular, metabolic, and respiratory diseases. We determined key parameters to reduce the number of spurious correlations and identified 7 statistically significant associations of reduced hospitalization risk after correcting for multiple testing. Some of these associations were already reported in other studies, including new potential applications for cardioselective beta-blockers and thiazides. We also found evidence for proton pump inhibitor side effects and multiple possible associations for anti-diabetic drugs. Our work demonstrates the applicability of the present screening approach and the utility of real-world data for identifying potential DR candidates.

Feasibility, acceptability, and outcome responsiveness of the SYMPERHEART intervention to support symptom perception in persons with heart failure and their informal caregivers: a feasibility quasi-experimental study.

BACKGROUND: Symptom perception is an important process of heart failure (HF) self-care that persons with HF need in order to master self-care management. It also leads to better patient outcomes. Symptom perception consists of body observation and analysis, which are both challenging. We aimed to test the feasibility, acceptability, and outcome responsiveness of a novel intervention (SYMPERHEART) delivered to persons with HF with their informal caregiver. METHODS: We designed SYMPERHEART as a complex evidence-informed education and support intervention targeting body observation and analysis. We conducted a feasibility quasi-experimental study with a single group pre-post-test design. We included three subsamples: persons with HF receiving home-based care, their informal caregivers exposed to SYMPERHEART, and home-care nurses who delivered SYMPERHEART during 1 month. We assessed feasibility by recruitment time, time to deliver SYMPERHEART, eligibility rate, and intervention fidelity. We assessed acceptability by consent rate, retention rate, persons with HF engagement in body observation, and treatment acceptability. Outcome responsiveness was informed by patient-reported (PRO) and clinical outcomes: HF self-care and the informal caregivers' contribution to HF self-care, perception of HF symptom burden, health status, caregivers' burden, and HF events. We performed descriptive analyses for quantitative data and calculated Cohen's d for PROs. A power analysis estimated the sample size for a future full-scale effectiveness study. RESULTS: We included 18 persons with HF, 7 informal caregivers, and 9 nurses. Recruitment time was 112.6 h. The median time to deliver SYMPERHEART for each participant was 177.5 min. Eligibility rate was 55% in persons with HF. Intervention fidelity revealed that 16 persons with HF were exposed to body observation and analysis. Consent and retention rates in persons with HF were 37.5% and 100%, respectively. Participants engaged actively in symptom and weight monitoring. Treatment acceptability scores were high. Symptom perception and informal caregivers' contribution to symptom perception were found to be responsive to SYMPERHEART. We estimate that a sample size of 50 persons with HF would be needed for a full-scale effectiveness study. CONCLUSIONS: SYMPERHEART was found to be feasible and acceptable. This feasibility study provides information for a subsequent effectiveness study. TRIAL REGISTRATION: ISRCTN. ISRCTN18151041 , retrospectively registered on 4 February 2021, ICTRP Search Portal.

Cytokine storm complicated by cardiogenic shock induced by anti-HER2 therapies.

Cytokine storm induced by anti-human epidermal growth factor receptor-2 (HER2) therapies has not been reported. We report a patient with breast cancer treated with trastuzumab/pertuzumab who developed severe biventricular dysfunction and cardiogenic shock (CS) 6 months after starting double anti-HER2 therapy. The CS was accompanied by severe systemic inflammation, and cardiac MRI (cMRI) showed structural changes typical of myocardial inflammation. The immuno-inflammatory profile showed significantly increased levels of activation of the complement system, proinflammatory cytokines (IL-1ß, IL-6, IL-18, IL-17A, TNF-alpha) with increased activity of classical monocytic, T helper 17 cells (Th17), CD4 T and effector memory CD8 T subsets, whereas NK cell activation was not observed. The data suggest an important role for monocytes as initiators of this FcγR-dependent antibody-dependent cytotoxicity, leading to the overactivation of an adaptive T cell response, in which Th17 cells may act in synergy with T helper 1 cells (Th1) to drive the severe cytokine release syndrome. After discontinuation of trastuzumab/pertuzumab, hypercytokinemia and complement activity normalized along with clinical recovery. Cardiac function returned to baseline within 2 months of initial presentation, together with a resolution of the myocardial inflammation on MRI.

[Cardiology: what's new in 2022]. / Cardiologie : ce qui a changé en 2022.

The year of 2022 was marked by many novelties in the fields of interventional cardiology, heart failure, electrophysiology, cardiac imaging, and congenital heart disease. These advances will certainly change our daily practice, on top of improving the diagnosis and treatment of many heart conditions. In addition, the European Society of Cardiology has updated its guidelines on pulmonary hypertension, ventricular arrhythmias and sudden death, cardiovascular assessment of patients undergoing non-cardiac surgery. The members of the Cardiology division of Lausanne University Hospital (CHUV) here present the publications which they considered to be the most important of the past year.

L'année 2022 a été marquée par de nombreuses nouveautés dans les domaines de la cardiologie interventionnelle, de l'insuffisance cardiaque, de l'électrophysiologie, de l'imagerie cardiaque et des cardiopathies congénitales. Ces progrès vont certainement faire évoluer notre pratique quotidienne, en plus d'améliorer le diagnostic et le traitement de nombreuses cardiopathies. Par ailleurs, la Société européenne de cardiologie a mis à jour ses recommandations portant sur l'hypertension pulmonaire, les arythmies ventriculaires et la mort subite ainsi que le bilan cardiologique avant une chirurgie non cardiaque. Les membres du Service de cardiologie du CHUV vous présentent ici les travaux qui leur ont semblé être les plus importants de l'année écoulée.

Post-transplant survival with pre-transplant durable continuous-flow mechanical circulatory support in a Swiss cohort of heart transplant recipients.

BACKGROUND: Worldwide, almost half of all heart transplantation candidates arrive today at their transplant operation with durable continuous-flow mechanical circulatory support (CF-MCS). This evolution is due to a progressive increase of waiting list time and hence an increased risk of haemodynamic worsening. Longer duration of CF-MCS is associated with a higher risk of device-related complications with potential adverse impact on post-transplant outcome as suggested by recent results from the United Network of Organ Sharing of the United States. METHODS: A 2-centre Swiss heart transplantation programme conducted a retrospective observational study of consecutive patients of theirs who underwent a transplant in the period 2008-2020. The primary aim was to determine whether post-transplant all-cause mortality is different between heart transplant recipients without or with pre-transplant CF-MCS. The secondary outcome was the acute cellular rejection score within the first year post-transplant. RESULTS: The study participants had a median age of 54 years; 38/158 (24%) were females. 53/158 study participants (34%) had pre-transplant CF-MCS with a median treatment duration of 280 days. In heart transplant recipients with pre-transplant CF-MCS, the prevalence of ischaemic cardiomyopathy was higher (51 vs 32%; p = 0.013), the left ventricular ejection fraction was lower (20 vs 25; p = 0.047) and pulmonary vascular resistance was higher (2.3 vs 2.1 Wood Units; p = 0.047). Over the study period, the proportion of heart transplant recipients with pre-transplant CF-MCS and the duration of pre-transplant CF-MCS treatment increased (2008-2014 vs 2015-2020: 22% vs 45%, p = 0.009; increase of treatment days per year: 34.4 ± 11.2 days, p = 0.003; respectively). The primary and secondary outcomes were not different between heart transplant recipients with pre-transplant CF-MCS or direct heart transplantation (log-rank p = 0.515; 0.16 vs 0.14, respectively; p = 0.81). CONCLUSION: This data indicates that the strategy of pre-transplant CF-MCS with subsequent orthotopic heart transplantation provides post-transplant outcomes not different to direct heart transplantation despite the fact that the duration of pre-transplant assist device treatment has progressively increased.

[Treatment of congestive heart failure in older persons and SGLT2 inhibitors - Having your patient's best interests at heart]. / Traitement de l'insuffisance cardiaque chez la personne âgée et inhibiteurs du SGLT2 - En avoir le cœur net.

The treatment and management of heart failure (HF) are constantly evolving. The latest guidelines recommend the use of SGLT2 inhibitors (SGLT2i) as an integral part to treating HF with reduced ejection fraction (< 40%). However, given that the patients included in these trials do not reflect the heterogeneity of the health of many elderly patients, we recommend basing the therapeutic decision on the patient's state of frailty. If a SGLT2i treatment at a standard dose (10 mg 1x/day) is recommended for robust patients, we suggest initiating treatment at 5 mg 1x/day for vulnerable patients, and then after 1 month increasing the dose to 10 mg 1x/day. Finally, for dependent patients, we recommend therapeutic abstention in the absence of sufficient scientific evidence.

La prise en charge de l'insuffisance cardiaque (IC) est en constante évolution. Les dernières recommandations préconisent l'utilisation des inhibiteurs du SGLT2 (iSGLT2) pour le traitement de l'IC à fraction d'éjection réduite (< 40%). Cependant, les populations des études ne reflètent pas l'hétérogénéité de la population âgée en termes de santé et nous proposons de baser la décision thérapeutique selon la Clinical Frailty Scale : si, pour les patients robustes, un traitement par iSGLT2 à dose standard (10 mg 1 x/jour) est préconisé, nous proposons, pour les patients vulnérables, d'initier le traitement à 5 mg 1 x/jour, puis d'augmenter à 10 mg 1 x/jour après 1 mois. Finalement, pour les patients dépendants, nous recommandons une abstention thérapeutique en l'absence d'évidences scientifiques suffisantes.

Decongestion improving right heart function ameliorates prognosis after an acute heart failure episode.

BACKGROUND: The prognostic role of decongestion-related change of cardiac morphology and in particular right heart function has not been investigated comprehensively in AHF patients. METHODS AND RESULTS: This prospective observational single-centre study included consecutive patients hospitalized for treatment of AHF with reduced, mildly-reduced or preserved left ventricular ejection fraction (LVEF). Comprehensive transthoracic echocardiography at admission and discharge assessed decongestion-related change of cardiac function and morphology. The combined endpoint of 1 year all-cause mortality and cardiovascular rehospitalization explored the prognostic importance of decongestion-related change. The 176 study participants were 83 years old [74-87] and 54% were men. Fifty one (29%) had rLVEF, 65 (37%) mrLVEF, and 60 (34%) pLVEF. The proportion of de novo or worsening chronic HF was not different between LVEF groups. HF aetiology and cardiovascular risk factors were equally distributed across all groups except for a higher BMI in the pLVEF group. Decongestion equally reduced body weight, heart rate, systolic and diastolic blood pressure, tricuspid regurgitation gradient, and inferior vena cava diameter across all groups (P < 0.004 for all). Decongestion-related increase in TAPSE independent of the LVEF was associated with improvement of right-ventricular-pulmonary artery coupling and a lower incidence of the combined outcome in the Cox proportional hazard risk analysis (unadjusted HR 0.50 95% CI 0.33-0.78, P = 0.002; adjusted HR 0.46 95% CI: 0.33-0.78, P = 0.001). CONCLUSIONS: Decongestion-related increase in TAPSE and recovery of RV/pulmonary artery coupling was observed across all LVEF groups and associated with a risk reduction for the combined endpoint highlighting the important prognostic role of right heart recovery after an AHF episode.

The Cardiomyocyte in Heart Failure with Preserved Ejection Fraction-Victim of Its Environment?

Heart failure (HF) with preserved left ventricular ejection fraction (HFpEF) is becoming the predominant form of HF. However, medical therapy that improves cardiovascular outcome in HF patients with almost normal and normal systolic left ventricular function, but diastolic dysfunction is missing. The cause of this unmet need is incomplete understanding of HFpEF pathophysiology, the heterogeneity of the patient population, and poor matching of therapeutic mechanisms and primary pathophysiological processes. Recently, animal models improved understanding of the pathophysiological role of highly prevalent and often concomitantly presenting comorbidity in HFpEF patients. Evidence from these animal models provide first insight into cellular pathophysiology not considered so far in HFpEF disease, promising that improved understanding may provide new therapeutical targets. This review merges observation from animal models and human HFpEF disease with the intention to converge cardiomyocytes pathophysiological aspects and clinical knowledge.

Cardiac Surgery in Advanced Heart Failure.

Mechanical circulatory support and heart transplantation are established surgical options for treatment of advanced heart failure. Since the prevalence of advanced heart failure is progressively increasing, there is a clear need to treat more patients with mechanical circulatory support and to increase the number of heart transplantations. This narrative review summarizes recent progress in surgical treatment options of advanced heart failure and proposes an algorithm for treatment of the advanced heart failure patient at >65 years of age.

[Cardiology]. / Cardiologie.

Significant advances have been made in 2021 in the areas of interventional cardiology, heart failure, cardiac imaging, electrophysiology and congenital heart disease. In addition to improving the screening, diagnosis and management of many heart diseases, these advances will change our daily practice. Moreover, the European Society of Cardiology has updated its guidelines on heart failure, valve disease, cardiac pacing and cardiovascular disease prevention. As in previous years, members of the Cardiology division of Lausanne University Hospital (CHUV) came together to select and present to you the papers that they considered to be the most important of the past year.

De nombreux progrès ont été réalisés en 2021 dans les domaines de la cardiologie interventionnelle, de l'insuffisance cardiaque, de l'imagerie cardiaque, de l'électrophysiologie et des cardiopathies congénitales. En plus d'améliorer le dépistage, le diagnostic et la prise en charge de nombreuses cardiopathies, ces avancées vont faire évoluer notre pratique quotidienne. Par ailleurs, la Société européenne de cardiologie a mis à jour ses recommandations portant sur l'insuffisance cardiaque, les valvulopathies, la stimulation cardiaque et la prévention des maladies cardiovasculaires. Comme les années précédentes, les membres du Service de cardiologie du CHUV se sont réunis pour sélectionner et vous présenter les travaux qui leur ont semblé être les plus importants de l'année écoulée.

Has the profile of heart transplantation recipients changed within the last three decades?

BACKGROUND: Heart transplantation remains the most durable treatment for patients with end-stage heart failure refractory to medical treatment. Central elements of the listing criteria for heart transplantation have remained largely unchanged in the last three decades whereas treatment of heart failure has significantly increased survival and reduced disease-related symptoms. It remains unknown whether the improvement of heart failure therapy changed the profile of heart transplantation candidates or affected post-transplant survival. METHODS: The study investigated a total of 323 heart transplant recipients of the Lausanne University Hospital with 328 transplant operations between 1987 and 2018. Patients were separated into three groups on the basis of availability of heart failure therapy: period 1 (1987-1998; n = 115) when renin-angiotensin system blockade and diuretic treatment were available; period 2 (1999-2010; n = 106) marked by the addition of beta-blocker and mineralocorticoid receptor antagonist treatment in severe heart failure, and the establishment of cardiac defibrillator and resynchronisation therapy; period 3 (2011-2018; n = 107) characterised by the increasing use of ventricular assist devices for bridge to transplantation. RESULTS: The patient characteristics age (all: 53.4 years), male sex (all: 79%) and body mass index (all: 24.5 kg/m2) did not differ between periods. History of arterial hypertension was less prevalent in period 2 (period 1 vs 2 vs 3: 44 vs 28 vs 43%, p = 0.04) whereas other cardiovascular risk factors were equally distributed. Left ventricular ejection fraction, VO2max, and pulmonary vascular resistance were not different between the three periods. The prevalence of ischaemic cardiomyopathy was higher in periods 1 and 3; dilated non-ischaemic cardiomyopathy was more frequent in period 2. Post-transplant 1-year survival was highest in period 3 (1 vs 2 vs 3: 87.2 ± 3.2% vs 70.8 ± 4.4% vs 93.0 ± 2.6%, p always ≤0.02), and the Kaplan-Meier estimates of survivors of the first year post-transplant were not different between the three periods. In descriptive analysis, early mortality was not associated with acknowledged pretransplant predictors of post-transplant mortality. CONCLUSION: Availability of different medical heart failure treatments did not result in greatly different pretransplant characteristics of heart transplantation recipients across the three periods. This suggests that the maintained central criteria of listing for heart transplantation still identify end-stage heart failure patients with a similar profile. This finding can explain the unchanged overall mortality on condition of 1-year survival across the three periods, since pretransplant characteristics are relevant for long-term survival after heart transplantation.

Complement blockade with eculizumab to treat acute symptomatic humoral rejection after heart transplantation.

Antibody-mediated rejection (AMR) is a major barrier preventing successful discordant organ xenotransplantation, but it also occurs in allotransplantation due to anti-HLA antibodies. Symptomatic acute AMR is rare after heart allograft but carries a high risk of mortality, especially >1 year after transplant. As complement activation may play a major role in mediating tissue injury in acute AMR, drugs blocking the terminal complement cascade like eculizumab may be useful, particularly since "standards of care" like plasmapheresis are not based on strong evidence. Eculizumab was successfully used to treat early acute kidney AMR, a typical condition of "active AMR," but showed mitigated results in late AMR, where "chronic active" lesions are more prevalent. Here, we report the case of a heart recipient who presented with acute heart failure due to late acute AMR with eight de novo donor-specific anti-HLA antibodies (DSA), and who fully recovered allograft function and completely cleared DSA following plasmapheresis-free upfront eculizumab administration in addition to thymoglobulin, intravenous immunoglobulins (IVIG), and rituximab. Several clinical (acute onset, abrupt and severe loss of graft function), biological (sudden high-level production of DSA), and pathological features (microvascular injury, C4d deposits) of this cardiac recipient are shared with early kidney AMR and may indicate a strong role of complement in the pathogenesis of acute graft injury that may respond to drugs like eculizumab. Terminal complement blockade should be further explored to treat acute AMR in recipients of heart allografts and possibly also in recipients of discordant xenografts in the future.

IgA Vasculitis With Henoch-Schönlein Purpura as an Immune Complication Associated With Left Ventricle Assist Device Insertion.

The implantation of left ventricular assist devices (LVADs) in patients with end-stage heart failure can be associated with some forms of immune dysregulation and systemic inflammatory response. These abnormalities may be related to impaired T-lymphocyte-dependent immunity and B-lymphocyte hyper-reactivity and may lead to the development of autoimmune processes and the occurrence of severe infections. We present here the first observation of a peculiar immune complication associated with the implantation of an LVAD, characterized by an IgA vasculitis clinically manifested as Henoch-Schönlein purpura. The vasculitis was biologically associated with a significant increase of the plasma levels of C-X-C motif chemokine ligand (CXCL)13, a CXC motif chemokine produced by follicular dendritic cells, which targets CXCR5, a receptor primarily expressed by B lymphocytes, to promote their chemotaxis and expansion. Spontaneous resolution of the vasculitis occurred over time, concomitantly to a decrease of CXCL13 expression. These findings suggest that CXCL13 might be an interesting biomarker to detect auto-antigen sampling and the risk of secondary immune complications following LVAD implantation.

Body composition and maximal exercise capacity after heart transplantation.

AIMS: Maximal exercise capacity as measured by peak oxygen consumption (pVO2 ) in cardiopulmonary exercise testing (CPET) of heart transplant recipients (HTR) is limited to a 50-70% level of healthy age-matched controls. This study investigated the relationship between body composition and pVO2 during the first decade post-transplant. METHODS AND RESULTS: Body composition was determined by dual-energy X-ray absorptiometry (DXA) and pVO2 by CPET in 48 HTR (n = 38 males; mean age 51 ± 12 years). A total of 95 assessments were acquired 1-9 years post-transplant, and the results of four consecutive periods were compared [Period 1: 1-2 years (n = 25); 2: 3-4 years (n = 23); 3: 5-6 years (n = 23); 4: 7-9 years (n = 24)]. Linear regression analysis analysed the correlation between pVO2 and pairs of appendicular lean mass (ALM) and fat mass (FM). The relation between ALM and daily dose of calcineurin inhibitor (CNI) was explored using partial correlation controlling for age, gender, and height. pVO2 increased from 0.98 (0.34) to 1.35 (0.35) L/min (P < 0.01) between Periods 1 and 4 corresponding to 54.5-63.3% of predicted value. Peak heart rate (HR) raised from 115 ± 19 to 131 ± 23 b.p.m. (P = 0.05), and anaerobic threshold (AT = VO2 achieved at AT) increased from 0.57 (0.18) to 0.83 (0.35) L/min (P < 0.01) between Periods 1 and 3. Median FM normalized to height2 (FMI) always remained elevated (>8.8 kg/m2 ). ALM normalized to body mass index increased from 0.690 (0.188) to 0.848 (0.204) m2 (P = 0.02) between Periods 1 and 4, explaining 45% of the variance of pVO2 (R2  = 0.455; P < 0.001). Eighty-one per cent of the variance of pVO2 (R2  = 0.817; P < 0.001) in multiple regression was explained by AT (ß = 0.488), ALM (ß = 0.396), peak HR (ß = 0.366), and FMI (ß = -0.181). ALM was negatively correlated with daily CNI dose (partial R = -0.258; P = 0.01). CONCLUSIONS: After heart transplantation, the beneficial effect of peripheral skeletal muscle gain on pVO2 is opposed by increased FM. Our findings support lifestyle efforts to fight adiposity and CNI dose reduction in the chronic stable phase to favour positive adaptation of peripheral muscle mass.