Waitlist Outcomes in Candidates With Rare Causes of Heart Failure After Implementation of the 2018 French Heart Allocation Scheme.

BACKGROUND: In 2018, an algorithm-based allocation system for heart transplantation (HT) was implemented in France. Its effect on access to HT of patients with rare causes of heart failure (HF) has not been assessed. METHODS: In this national study, including adults listed for HT between 2018 and 2020, we analyzed waitlist and posttransplant outcomes of candidates with rare causes of HF (restrictive cardiomyopathy [RCM], hypertrophic cardiomyopathy, and congenital heart disease). The primary end point was death on the waitlist or delisting for clinical deterioration. Secondary end points included access to HT and posttransplant mortality. The cumulative incidence of waitlist mortality estimated with competing risk analysis and incidence of transplantation were compared between diagnosis groups. The association of HF cause with outcomes was determined by Fine-Gray or Cox models. RESULTS: Overall, 1604 candidates were listed for HT. At 1 year postlisting, 175 patients met the primary end point and 1040 underwent HT. Candidates listed for rare causes of HF significantly differed in baseline characteristics and had more frequent score exceptions compared with other cardiomyopathies (31.3%, 32.0%, 36.4%, and 16.7% for patients with hypertrophic cardiomyopathy, RCM, congenital heart disease, and other cardiomyopathies). The cumulative incidence of death on the waitlist and probability of HT were similar between diagnosis groups (P=0.17 and 0.40, respectively). The adjusted risk of death or delisting for clinical deterioration did not significantly differ between candidates with rare and common causes of HF (subdistribution hazard ratio (HR): hypertrophic cardiomyopathy, 0.51 [95% CI, 0.19-1.38]; P=0.18; RCM, 1.04 [95% CI, 0.42-2.58]; P=0.94; congenital heart disease, 1.82 [95% CI, 0.78-4.26]; P=0.17). Similarly, the access to HT did not significantly differ between causes of HF (hypertrophic cardiomyopathy: HR, 1.18 [95% CI, 0.92-1.51]; P=0.19; RCM: HR, 1.19 [95% CI, 0.90-1.58]; P=0.23; congenital heart disease: HR, 0.76 [95% CI, 0.53-1.09]; P=0.14). RCM was an independent risk factor for 1-year posttransplant mortality (HR, 2.12 [95% CI, 1.06-4.24]; P=0.03). CONCLUSIONS: Our study shows equitable waitlist outcomes among HT candidates whatever the indication for transplantation with the new French allocation scheme.

Heart graft preservation technics and limits: an update and perspectives.

Heart transplantation, the gold standard treatment for end-stage heart failure, is limited by heart graft shortage, justifying expansion of the donor pool. Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard practice, but it is usually limited to 240 min. Prolonged cold ischemia and ischemia-reperfusion injury (IRI) have been recognized as major causes of post-transplant graft failure. Continuous ex situ perfusion is a new approach for donor organ management to expand the donor pool and/or increase the utilization rate. Continuous ex situ machine perfusion (MP) can satisfy the metabolic needs of the myocardium, minimizing irreversible ischemic cell damage and cell death. Several hypothermic or normothermic MP methods have been developed and studied, particularly in the preclinical setting, but whether MP is superior to SCS remains controversial. Other approaches seem to be interesting for extending the pool of heart graft donors, such as blocking the paths of apoptosis and necrosis, extracellular vesicle therapy, or donor heart-specific gene therapy. In this systematic review, we summarize the mechanisms involved in IRI during heart transplantation and existing targeting therapies. We also critically evaluate all available data on continuous ex situ perfusion devices for adult donor hearts, highlighting its therapeutic potential and current limitations and shortcomings.

Evaluation of 18-FDG PET diagnostic capabilities for cancer screening in heart transplant patients, a retrospective study.

Evaluate 18-FDG positron emission tomography (PET) diagnostic capabilities for cancer screening in heart transplant patients. We conducted an anonymized retrospective observational study of heart transplant patients followed in the University Hospital of Montpellier, France. We analyzed 303 18-FDG PET from 158 patients. We compared demographic and clinical characteristics through uni- and multivariate analysis: in the cancer-free group, comparisons were made between the PET false positive (FP) group versus true negative (TN), and in the cancer group, comparisons were made between the PET false negative (FN) group versus true positive (TP). Out of the 303 exams, we found 245 TN, 26 TP, 26 FP and 6 FN. The sensitivity rate was calculated at 81%, the specificity rate at 90%, the positive predictive value at 50%, and the negative predictive value at 97%. The multivariate analysis showed an association between FP diagnosis and graft-PET delay (P value = .046, OR = 5.14, 95% CI [1.18-32.4]) and creatine reactive protein (CRP) ≥ 10 mg/L (P value = .042, OR = 4.21, 95% CI [1.02-17.2]). The estimated probability of FP by logit regression was 0.48 with 95% CI [0.21-0.77] when graft-PET delay ≥ 6 years and CRP ≥ 10 mg/L. No significative statistical link was found for the demographic or clinical characteristics in the FN group of patients with cancer, except for sex (all FN were men). 18-FDG PET performed very well in the follow-up of heart transplant patients for neoplasia screening, with better specificity than sensitivity. However, the study showed that almost 50% of FP can be predicted by considering only the graft-PET delay and CRP.

Preservation of Organs to Be Transplanted: An Essential Step in the Transplant Process.

Organ transplantation remains the treatment of last resort in case of failure of a vital organ (lung, liver, heart, intestine) or non-vital organ (essentially the kidney and pancreas) for which supplementary treatments exist. It remains the best alternative both in terms of quality-of-life and life expectancy for patients and of public health expenditure. Unfortunately, organ shortage remains a widespread issue, as on average only about 25% of patients waiting for an organ are transplanted each year. This situation has led to the consideration of recent donor populations (deceased by brain death with extended criteria or deceased after circulatory arrest). These organs are sensitive to the conditions of conservation during the ischemia phase, which have an impact on the graft's short- and long-term fate. This evolution necessitates a more adapted management of organ donation and the optimization of preservation conditions. In this general review, the different aspects of preservation will be considered. Initially done by hypothermia with the help of specific solutions, preservation is evolving with oxygenated perfusion, in hypothermia or normothermia, aiming at maintaining tissue metabolism. Preservation time is also becoming a unique evaluation window to predict organ quality, allowing repair and/or optimization of recipient choice.

Idarucizumab (Praxbind®) for dabigatran reversal in patients undergoing heart transplantation: a cohort of ten patients.

BACKGROUND: Novel oral anticoagulants are used in atrial fibrillation. Idarucizumab has been approved for reversal of dabigatran in situations of life-threatening hemorrhage or emergency surgery. OBJECTIVES: We report a single center experience of ten patients on dabigatran therapy who were given idarucizumab prior to heart transplantation. METHODS & RESULTS: The mean plasma concentration of dabigatran prior to reversal was 139 ± 89 ng/ml. Hemoglobin, hematocrit and platelet levels were decreased after surgery. Surgical procedures were successfully performed with no increased risk, especially regarding bleeding complications. All patients were alive after 90 days. CONCLUSION: Dabigatran reversal with idarucizumab in contexts of emergency surgery/urgent procedures is an attractive and safe option to be taken into consideration for patients with end stage heart disease awaiting transplantation and indication of anticoagulant therapy.

PRADOC: a trial on the efficiency of a transition care management plan for hospitalized patients with heart failure in France.

AIMS: Transition care programmes are designed to improve coordination of care between hospital and home. For heart failure patients, meta-analyses show a high efficacy but with moderate evidence level. Moreover, difficulties for implementation of such programmes limit their extrapolation. METHODS AND RESULTS: We designed a mixed-method study to assess the implementation of the PRADO-IC, a nationwide transition programme that aims to be offered to every patient with heart failure in France. This programme consists essentially in an administrative assistance to schedule follow-up visits and in a nurse follow-up during 2 to 6 months and aims to reduce the annual heart failure readmission rate by 30%. This study assessed three quantitative aims: the cost to avoid a readmission for heart failure within 1 year (primary aim, intended sample size 404 patients), clinical care pathways, and system economic outcomes; and two qualitative aims: perceived problems and benefits of the PRADO-IC. All analyses will be gathered at the end of study for a joint interpretation. Strengths of this study design are the randomized controlled design, the population included in six centres with low motivation bias, the primary efficiency analysis, the secondary efficacy analyses on care pathway and clinical outcomes, and the joint qualitative analysis. Limits are the heterogeneity of centres and of intervention in a control group and parallel development of other new therapeutic interventions in this field. CONCLUSIONS: The results of this study may help decision-makers to support an administratively managed transition programme.

Multimarker approach including CRP, sST2 and GDF-15 for prognostic stratification in stable heart failure.

AIMS: Inflammation and cardiac remodelling are common and synergistic pathways in heart failure (HF). Emerging biomarkers such as soluble suppression of tumorigenicity 2 (sST2) and growth differentiation factor-15 (GDF-15), which are linked to inflammation and fibrosis process, have been proposed as prognosis factors. However, their potential additive values remain poorly investigated. METHODS AND RESULTS: Here, we aimed at evaluating inflammatory and remodelling biomarkers to predict both short-term and long-term mortality in a population with chronic HF in comparison with other classical clinical or biological markers (i.e. N terminal pro brain natriuretic peptide, hs-cTnT, C-reactive protein) alone or using meta-analysis global group in chronic HF risk score in a cohort of 182 patients followed during 80 months (interquartile range: 12.3-90.0). Proportional hazard assumption does not hold for sST2 and C-reactive protein, and follow-up was split into short term (less than 1 year), midterm (between 1 and 5 years), and long term (after 5 years). In univariate analysis, C-reactive protein and sST2 were predictive of short-term mortality but not of middle term and long term whereas GDF-15 was predictive of short and mid-term but not of long-term mortality. In a multivariate model after adjustment for meta-analysis global group in chronic HF score including the three markers, only sST2 was predictive of short-term mortality (P = 0.0225), and only GDF-15 was predictive of middle term mortality (P = 0.0375). None of the markers was predictive of long-term mortality. CONCLUSIONS: Our results demonstrate that both sST2 and GDF-15 significantly improve the prognosis evaluation of HF patients and suggest that the value of GDF-15 is more sustained overtime and could predict middle term events.

STADE-HF (sST2 As a help for management of HF): a pilot study.

AIMS: Biomarkers are not recommended until now to guide the management of patients with heart failure (HF). Soluble suppression of tumorigenicity 2 (sST2) appears as a promising biomarker. The current study considered pre-discharged sST2 values as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to reduce hospital readmission. METHODS AND RESULTS: STADE-HF was a blinded prospective randomized controlled trial and included 123 patients admitted for acute HF. They were randomized into the usual treatment group (unknown sST2 level) or the interventional treatment group, for whom sST2 level was known and used on Day 4 of hospitalization to guide the treatment. The primary endpoint was the readmission rate for any cause at 1 month. It occurred in 10 patients (19%) in the usual group and 18 (32%) in the sST2 group without statistical difference (P = 0.11). Post hoc analysis in the whole group shows that the mean duration of hospitalization was lower in patients with low sST2 (<37 ng/mL) at admission vs. high sST2 (8.5 ± 9.5 vs. 14.8 ± 14.9 days, respectively, P = 0.003). In addition, a decrease in sST2 greater than 18% is significantly associated with a lower readmission rate. CONCLUSIONS: Soluble suppression of tumorigenicity 2-guided therapy over a short period of time does not reduce readmissions. However, sST2 was clearly associated with duration of hospitalization, and the decrease in sST2 was associated with decreased rehospitalizations. Long-term outcome using sST2-guided therapy deserves further investigations.

Management of advanced heart failure: a review.

INTRODUCTION: Heart failure (HF) has become a global pandemic. Despite recent developments in both medical and device treatments, HF incidences continues to increase. The current definition of HF restricts itself to stages at which clinical symptoms are apparent. In advanced heart failure (AdHF), it is universally accepted that all patients are refractory to traditional therapies. As the number of HF patients increase, so does the need for additional treatments, with an increased proportion of patients requiring advanced therapies. Areas covered: This review discusses extensive evidence for the effect of medical treatment on HF, although the data on the effect on AdHF is scare. Authors review the relevant literature for treating AdHF patients. Furthermore, mechanical circulatory devices (MCD) have emerged as an alternative to heart transplantation and have been shown to enhance quality of life and reduce mortality therefore authors also review the current literature on the different MCD and technologies. Expert commentary: More patients will need advanced therapies, as the access to heart transplantation is limited by the number of available donors. AdHF patients should be identified timely since the window of opportunities for advanced therapy is narrow as their morbidity is progressive and survival is often short.

Right coronary cusp perforation after mitral valve replacement.

Secondary to leaflet injury, which is a well-known technical mistake, aortic regurgitation can occur during mitral valve replacement or repair. In most cases, the left or the non-coronary cusps are affected. For the first time, we report the case of a patient who had severe aortic regurgitation due to right coronary cusp perforation after mitral valve replacement. This complication was not identified until reoperation. Had transoesophageal echocardiography (TOE) been used during the first procedure, a delayed reoperation could have been avoided. During mitral surgery, every aortic cusp is at risk and peroperative TOE should be a mandatory procedure.

Fatal systemic nocardia infection revealed by cardiac tamponade.

We report the case of a 50-year-old man admitted for cardiac tamponade. He was diagnosed with acute pneumonia. He had no previous medical history, but exhibited a body mass index of 41. Two days before admission, he complained of chest pain irradiating to the neck lateral side. Massive cardiac tamponade developed over 48 hours. There was no obvious cause for immunodepression. Pericardial puncture was ineffective, due to obesity and fluid high viscosity. Surgery was undertaken (Marfan intervention). Pericardial fluid was found to be purulent; direct examination revealed nocardia as bacteria with typical filamentous, branching rods. Despite adapted antibiotic treatment the patient died within a few hours. Acute pericarditis due to Nocardia is discussed.

Pacemaker surgical site infection caused by Mycobacterium goodii.

We describe what we believe to be the first documented case of Mycobacterium goodii infection in Europe. It is also the second documented report of a pacemaker pocket surgical site infection caused by M. goodii. Although rarely involved in such infections, rapidly growing mycobacteria should be recognized during conventional bacteriological investigations and further identified by molecular tools to provide adequate therapy. In the present case, antimicrobial therapy with doxycycline without removal of the pacemaker was successful.

Early postoperative assessment of coronary artery bypass graft patency and anatomy: value of contrast-enhanced 16-MDCT with retrospectively ECG-gated reconstructions.

OBJECTIVE: The objective of our study was to assess early postoperative patency and anatomy of off-pump coronary artery bypass grafts (CABGs) using retrospectively ECG-gated MDCT. CONCLUSION: Retrospectively ECG-gated MDCT is a promising noninvasive technique with which to assess early postoperative patency and anatomy of CABGs.

Pericardial exploration by pericardioscopy during a surgical sub xyphoid approach.

This clinical feasibility study was planned to evaluate pericardioscopy as a means of control of the pericardial cavity during drainage for pericardial effusion by a surgical sub xyphoid approach. Seventeen patients who underwent an operation for surgical drainage of the pericardium (11 medical and 6 postoperative pericardial effusions) benefited from a pericardial exploration with a mediastinoscope or rigid thoracoscope (Karl Storz, Germany). In 7 of the 11 medical cases, a severe inflammation of the pericardium associated with false membranes was visualized; in 3 cases, the pericardium was considered as normal; and in 1 case, pericardial metastases were visualized. In the 6 postoperative cases, clots were visualized with a venous bypass graft and the pulmonary cannula of a right ventricular assist device (Thoratec, USA) was also perfectly controlled. The cause of bleeding was reported in one case and suspected in another, but required total sternotomy for repair in both cases. No mortality or morbidity was reported to be directly due to the technique. The peroperative assessment of pericardial cavity is possible by use of pericardioscopy with a satisfactory resolution, but visualization of the left lateral part of the heart remains difficult. The possibility exists to partially remove clots and false membranes, obtain various samples, and control the position of the drains. Improvement in the optic device with the possibility of a flexible device that has a tip protector for optimal visualization, may improve both the technique and results.

Off-Pump Coronary Artery Bypass Grafts Assessment by Multislice Computed Tomography.

Abstract Background: Selective coronary angiography is the standard but invasive procedure for postoperative assessment of coronary artery bypass graft patency. The aim of this prospective study is to evaluate the multislice computed tomography (CT) as a means of postoperative patency assessment and anastomotic site control of arterial and venous coronary bypass grafts performed with off-pump coronary artery bypass techniques. Methods: Over a 6-month period, 20 patients underwent isolated coronary artery bypass (beating heart technique) and benefited, 7 days later, from a patency and anastomotic site control by multidetector angio multislice CT with cardiac gating. Results: Whole internal thoracic artery bypasses and venous grafts were visualized perfectly on their entire length, including the anastomotic site, and 3-dimensional reconstruction was possible. The relationship between cardiac cavities and the bypasses were well visualized, allowing quantification of bypass stenosis ensured by software analysis. Conclusions: Postoperative control of coronary bypasses is possible by multislice CT with a very satisfactory resolution, thus making it possible to check the patency of coronary bypasses and the quality of anastomosis with a noninvasive method. Three-dimensional reconstructions are very useful in the event of redo surgery.