A locally optimised machine learning approach to early prognostication of long-term neurological outcomes after out-of-hospital cardiac arrest.

Background: Out-of-hospital cardiac arrest (OHCA) represents a major burden for society and health care, with an average incidence in adults of 67 to 170 cases per 100,000 person-years in Europe and in-hospital survival rates of less than 10%. Patients and practitioners would benefit from a prognostication tool for long-term good neurological outcomes. Objective: We aim to develop a machine learning (ML) pipeline on a local database to classify patients according to their neurological outcomes and identify prognostic features. Methods: We collected clinical and biological data consecutively from 595 patients who presented OHCA and were routed to a single regional cardiac arrest centre in the south of France. We applied recursive feature elimination and ML analyses to identify the main features associated with a good neurological outcome, defined as a Cerebral Performance Category score less than or equal to 2 at six months post-OHCA. Results: We identified 12 variables 24 h after admission, capable of predicting a six-month good neurological outcome. The best model (extreme gradient boosting) achieved an AUC of 0.96 and an accuracy of 0.92 in the test cohort. Conclusion: We demonstrated that it is possible to build accurate, locally optimised prediction and prognostication scores using datasets of limited size and breadth. We proposed and shared a generic machine-learning pipeline which allows external teams to replicate the approach locally.

TAPSE/sPAP prognostic value for In-Hospital Adverse Events in Patients Hospitalized for Acute Coronary Syndrome.

AIMS: Although several studies have shown that the right ventricular to pulmonary artery (RV-PA) coupling, assessed by the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/sPAP) using echocardiography, is strongly associated with cardiovascular events, its prognostic value is not established in acute coronary syndrome (ACS). We aimed to assess the in-hospital prognostic value of TAPSE/sPAP among patients hospitalized for ACS in a retrospective analysis from the prospective ADDICT-ICCU study. METHODS AND RESULTS: 481 consecutive patients hospitalized in intensive cardiac care unit (mean age 65±13 years, 73% of male, 46% STEMI) for ACS (either ST-elevation [STEMI] or non-ST-elevation [NSTEMI] myocardial infarction) with TAPSE/sPAP available were included in this prospective French multicentric study (39 centers). The primary outcome was in-hospital major adverse cardiovascular events (MACEs) defined as all-cause death, resuscitated cardiac arrest or cardiogenic shock and occurred in 33 (7%) patients. ROC-curve analysis identified 0.55 mm/mmHg as the best TAPSE/sPAP cut-off to predict in-hospital MACEs. TAPSE/sPAP <0.55 was associated with in-hospital MACEs, even after adjustment with comorbidities (OR:19.1, 95%CI[7.78-54.8]), clinical severity including left ventricular ejection fraction (OR:14.4, 95%CI[5.70-41.7]) and propensity-matched population analysis (OR:22.8, 95%CI[7.83-97.2], all p<0.001). After adjustment, TAPSE/sPAP <0.55 showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.16; global chi-square improvement: 52.8; LR-test p<0.001) with similar results for both STEMI and NSTEMI subgroups. CONCLUSION: A low RV-PA coupling defined as TAPSE/sPAP ratio <0.55 was independently associated with in-hospital MACEs and provided incremental prognostic value over traditional prognosticators in patients hospitalized for ACS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05063097.

Cardiogenic shock and chronic kidney disease: Dangerous liaisons.

BACKGROUND: Chronic kidney disease (CKD) is one of the leading causes of death worldwide, closely interrelated with cardiovascular diseases, ultimately leading to the failure of both organs - the so-called "cardiorenal syndrome". Despite this burden, data related to cardiogenic shock outcomes in CKD patients are scarce. METHODS: FRENSHOCK (NCT02703038) was a prospective registry involving 772 patients with cardiogenic shock from 49 centres. One-year outcomes (rehospitalization, death, heart transplantation, ventricular assist device) were analysed according to history of CKD at admission and were adjusted on independent predictive factors. RESULTS: CKD was present in 164 of 771 patients (21.3%) with cardiogenic shock; these patients were older (72.7 vs. 63.9years) and had more comorbidities than those without CKD. CKD was associated with a higher rate of all-cause mortality at 1month (36.6% vs. 23.2%; hazard ratio 1.39, 95% confidence interval 1.01-1.9; P=0.04) and 1year (62.8% vs. 40.5%, hazard ratio 1.39, 95% confidence interval 1.09-1.77; P<0.01). Patients with CKD were less likely to be treated with norepinephrine/epinephrine or undergo invasive ventilation or receive mechanical circulatory support, but were more likely to receive renal replacement therapy (RRT). RRT was associated with a higher risk of all-cause death at 1month and 1year regardless of baseline CKD status. CONCLUSIONS: Cardiogenic shock and CKD are frequent "cross-talking" conditions with limited therapeutic options, resulting in higher rates of death at 1month and 1year. RRT is a strong predictor of death, regardless of preexisting CKD. Multidisciplinary teams involving cardiac and kidney physicians are required to provide integrated care for patients with failure of both organs.

Association between pulmonary artery pulsatility and mortality after implantation of left ventricular assist device.

AIMS: Right ventricular failure after left ventricular assist device (LVAD) implantation is a major concern that remains challenging to predict. We sought to investigate the relationship between preoperative pulmonary artery pulsatility index (PAPi) and mortality after LVAD implantation. METHODS AND RESULTS: A retrospective analysis of the ASSIST-ICD multicentre registry allowed the assessment of PAPi before LVAD according to the formula [(systolic pulmonary artery pressure - diastolic pulmonary artery pressure)/central venous pressure]. The primary endpoint was survival at 3 months, according to the threshold value of PAPi determined by the receiver operating characteristic (ROC) curve. A multivariate analysis including demographic, echographic, haemodynamic, and biological variables was performed to identify predictive factors for 2 year mortality. One hundred seventeen patients were included from 2007 to 2021. The mean age was 58.45 years (±13.16), with 15.4% of women (sex ratio 5.5). A total of 53.4% were implanted as bridge to transplant and 43.1% as destination therapy. Post-operative right ventricular failure was observed in 57 patients (48.7%), with no significant difference between survivors and non-survivors at 1 month (odds ratio 1.59, P = 0.30). The median PAPi for the whole study population was 2.83 [interquartile range 1.63-4.69]. The threshold value of PAPi determined by the ROC curve was 2.84. Patients with PAPi ≥ 2.84 had a higher survival rate at 3 months [PAPi < 2.84: 58.1% [46.3-72.8%] vs. PAPi ≥ 2.84: 89.1% [81.1-97.7%], hazard ratio (HR) 0.08 [0.02-0.28], P < 0.01], with no significant difference after 3 months (HR 0.67 [0.17-2.67], P = 0.57). Other predictors of 2 year mortality were systemic hypertension (HR 4.22 [1.49-11.97], P < 0.01) and diabetes mellitus (HR 4.90 [1.83-13.14], P < 0.01). LVAD implantation as bridge to transplant (HR 0.18 [0.04-0.74], P = 0.02) and heart transplantation (HR 0.02 [0.00-0.18], P < 0.01) were associated with a higher survival rate at 2 years. CONCLUSIONS: Preoperative PAPi < 2.84 was associated with a higher risk of early mortality after LVAD implantation without impacting 2 year outcomes among survivors.

The real incidence of sudden death: Fair estimations or futile speculations?

BACKGROUND: The true incidence of sudden death remains undetermined, with controversial results from various publications over time and countries. AIM: To investigate if different estimations would reach the values usually reported for France. METHODS: Three different kinds of estimations were used. First, the number of resuscitated sudden deaths and necropsies for sudden death in the Haute-Garonne French administrative department (i.e. county) over the last 10years was expanded to the national level. Second, sudden death coding of death certificates was collected at the national level. Third, the total number of out-of-hospital cardiac arrests leading to any emergency call (with/without intervention) in Haute-Garonne over the last 10years was expanded to the national level. RESULTS: There was a mean of 26 resuscitated sudden deaths and 145 necropsies for sudden death each year in Haute-Garonne, i.e. 12 to 14 sudden deaths for 100,000 inhabitants, and 7700 to 9400 sudden deaths yearly when related to the whole French population, according to the year of inclusion. Based on death certificates, a mean of 6584 sudden deaths was registered each year in France. Finally, there were about 600 yearly calls/interventions for out-of-hospital cardiac arrests in Haute-Garonne, i.e. 40 to 50 sudden deaths for 100,000 inhabitants, and 16,000 to 27,000 sudden deaths yearly for the whole French territory, according to the year of inclusion. CONCLUSIONS: The incidence of sudden death ranges from 6500 to 27,000 in France according to the calculation methods. This huge difference raises the question of the true current incidence of sudden death, which may have been overestimated previously or may be underestimated in France. More straight prospective surveys are needed to solve this question, because of relevant implications for priorities that should be given to sudden death.

Sex disparities in cardiogenic shock: Insights from the FRENSHOCK registry.

BACKGROUND: Cardiogenic shock (CS) is the most severe form of acute heart failure. Discrepancies have been reported between sexes regarding delays, pathways and invasive strategies in CS complicating acute myocardial infarction. However, effect of sex on the prognosis of unselected CS remains controversial. OBJECTIVES: The aim was to analyze the impact of sex on aetiology, management and prognosis of CS. METHODS: The FRENSHOCK registry included all CS admitted in 49 French Intensive Care Units (ICU) and Intensive Cardiac Care Units (ICCU) between April and October 2016. RESULTS: Among the 772 CS patients included, 220 were women (28.5%). Women were older, less smokers, with less history of ischemic cardiac disease (20.5% vs 33.6%) than men. At admission, women presented less cardiac arrest (5.5 vs 12.2%), less mottling (32.5 vs 41.4%) and higher LVEF (30 ± 14 vs 25 ± 13%). Women were more often managed via emergency department while men were directly admitted at ICU/ICCU. Ischemia was the most frequent trigger irrespective of sex (36.4% in women vs 38.2%) but women had less coronary angiogram and PCI (45.9% vs 54% and 24.1 vs 31.3%, respectively). We found no major difference in medication and organ support. Thirty-day mortality (26.4 vs 26.5%), transplant or permanent assist device were similar in both sexes. CONCLUSION: Despite some more favorable parameters in initial presentation and no significant difference in medication and support, women shared similar poor prognosis than men. Further analysis is required to cover the lasting gap in knowledge regarding sex specificities to distinguish between differences and inequalities. NCT02703038.

Profile of patients hospitalized in intensive cardiac care units in France: ADDICT-ICCU registry.

BACKGROUND: Intensive cardiac care units (ICCU) were initially developed to monitor ventricular arrhythmias after myocardial infarction. In recent decades, ICCU have diversified their activities. AIM: To determine the type of patients hospitalized in ICCU in France. METHODS: We analysed the characteristics of patients enrolled in the ADDICT-ICCU registry (NCT05063097), a prospective study of consecutive patients admitted to ICCU in 39 centres throughout France from 7th-22nd April 2021. In-hospital major adverse events (MAE) (death, resuscitated cardiac arrest and cardiogenic shock) were recorded. RESULTS: Among 1499 patients (median age 65 [interquartile range 54-74] years, 69.6% male, 21.7% diabetes mellitus, 64.7% current or previous smokers), 34.9% had a history of coronary artery disease, 11.7% atrial fibrillation and 5.2% cardiomyopathy. The most frequent reason for admission to ICCU was acute coronary syndromes (ACS; 51.5%), acute heart failure (AHF; 14.1%) and unexplained chest pain (6.8%). An invasive procedure was performed in 36.2%. "Advanced" ICCU therapies were required for 19.9% of patients (intravenous diuretics 18.4%, non-invasive ventilation 6.1%, inotropic drugs 2.3%). No invasive procedures or advanced therapies were required in 44.1%. Cardiac computed tomography or magnetic resonance imaging was carried out in 12.3% of patients. The median length of ICCU hospitalization was 2.0 (interquartile range 1.0-4.0) days. The mean rate of MAE was 4.5%, and was highest in patients with AHF (10.4%). CONCLUSIONS: ACS remains the main cause of admissions to ICCU, with most having a low rate of in-hospital MAE. Most patients experience a brief stay in ICCU before being discharged home. AHF is associated with highest death rate and with higher resource consumption.

Optimal Heart Failure Medical Therapy and Mortality in Survivors of Cardiogenic Shock: Insights From the FRENSHOCK Registry.

BACKGROUND: The effects of pharmacological therapy on cardiogenic shock (CS) survivors have not been extensively studied. Thus, this study investigated the association between guideline-directed heart failure (HF) medical therapy (GDMT) and one-year survival rate in patients who are post-CS. METHODS AND RESULTS: FRENSHOCK (French Observatory on the Management of Cardiogenic Shock in 2016) registry was a prospective multicenter observational survey, conducted in metropolitan French intensive care units and intensive cardiac care units. Of 772 patients, 535 patients were enrolled in the present analysis following the exclusion of 217 in-hospital deaths and 20 patients with missing medical records. Patients with triple GDMT (beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists) at discharge (n=112) were likely to have lower left ventricular ejection fraction on admission and at discharge compared with those without triple GDMT (n=423) (22% versus 28%, P<0.001 and 29% versus 37%, P<0.001, respectively). In the overall cohort, the one-year mortality rate was 23%. Triple GDMT prescription was significantly associated with a lower one-year all-cause mortality compared with non-triple GDMT (adjusted hazard ratio 0.44 [95% CI, 0.19-0.80]; P=0.007). Similarly, 2:1 propensity score matching and inverse probability treatment weighting based on the propensity score demonstrated a lower incidence of one-year mortality in the triple GDMT group. As the number of HF drugs increased, a stepwise decrease in mortality was observed (log rank; P<0.001). CONCLUSIONS: In survivors of CS, the one-year mortality rate was significantly lower in those with triple GDMT. Therefore, this study suggests that intensive HF therapy should be considered in patients following CS.

Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma.

The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood. Inflammation is potentially an important but still undervalued factor. Here, we present a first-in-human prospective study using the 18-kDa translocator protein (TSPO) radioligand 18F-DPA714 for PET imaging to allow in vivo neuroimmune activation quantification in patients with coma (n = 17) following either anoxia or traumatic brain injuries in comparison with age- and sex-matched controls. Our findings yielded novel evidence of an early inflammatory component predominantly located within key cortical and subcortical brain structures that are putatively implicated in consciousness emergence and maintenance after severe brain injury (i.e. mesocircuit and frontoparietal networks). We observed that traumatic and anoxic patients with coma have distinct neuroimmune activation profiles, both in terms of intensity and spatial distribution. Finally, we demonstrated that both the total amount and specific distribution of PET-measurable neuroinflammation within the brain mesocircuit were associated with the patient's recovery potential. We suggest that our results can be developed for use both as a new neuroprognostication tool and as a promising biometric to guide future clinical trials targeting glial activity very early after severe brain injury.

Use of the Win Ratio Analysis in Critical Care Trials.

Composite outcomes are commonly used in critical care trials to estimate the treatment effect of an intervention. A significant limitation of classical analytic approaches is that they assign equal statistical importance to each component in a composite, even if these do not have the same clinical importance (i.e., in a composite of death and organ failure, death is clearly more important). The win ratio (WR) method has been proposed as an alternative for trial outcomes evaluation, as it effectively assesses events based on their clinical relevance (i.e., hierarchical order) by comparing each patient in the intervention group with their counterparts in the control group. This statistical approach is increasingly used in cardiovascular outcome trials. However, WR may be useful to unveil treatment effects also in the critical care setting, because these trials are typically moderately sized, thus limiting the statistical power to detect small differences between groups, and often rely on composite outcomes that include several components of different clinical importance. Notably, the advantages of this approach may be offset by several drawbacks (such as ignoring ties and difficulties in selecting and ranking endpoints) and challenges in appropriate clinical interpretation (i.e., establishing clinical meaningfulness of the observed effect size). In this perspective article, we present some key elements to implementing WR statistics in critical care trials, providing an overview of strengths, drawbacks, and potential applications of this method. To illustrate, we conduct a reevaluation of the HYPO-ECMO (Hypothermia during Venoarterial Extracorporeal Membrane Oxygenation) trial using the WR framework as a case example.

Guideline adherence in the management of acute pulmonary oedema: Study protocol for a French survey involving cardiologists, emergency physicians and intensivists.

BACKGROUND: Because of their high morbidity and mortality, patients with acute pulmonary oedema (APE) require early recognition of symptoms, identification of precipitating factors and admission to specialized care units (cardiac critical care or intensive care). APE is at the crossroads of different specialties (cardiology, emergency medicine and intensive care medicine). Although multidisciplinary expertise and management may be a strength, it can also be a source of confusion, with unexpected heterogeneity in patient care. We hypothesized that the management of severe APE may be heterogeneous between specialties and, in some situations, may differ from international recommendations. AIM: We designed a survey to compare management of different APE phenotypes according to the physicians' medical specialty, and to compare the results with what experts would do and European guidelines. METHODS: Four clinical cases of typical APE with questions pertaining to the latest guidelines were designed by a Scientific Committee designated by the French Scientific Societies for Cardiology, Emergency Medicine and Intensive Care Medicine. We focused on oxygenation and ventilation strategies, management of precipitating factors, including timing of coronary revascularization, use of diuretics and management of diuretic resistance, and discharge coverage. From 20 June 2022 until 09 September 2022, the four cases of APE (two during hypertensive crises, two during acute coronary syndromes) were proposed to French physicians involved in APE care, and to experts, using an open online survey. To avoid any diagnostic ambiguity, the diagnosis of APE was given at the beginning of each clinical case. RESULTS: The intention is to present the results at national and international conferences and publish them in a peer-reviewed journal. CONCLUSIONS: The results of this survey are intended to pave the way for the generation of novel hypotheses for future clinical trials in case of equipoise between subsets of therapeutic procedures in APE.

Carbon monoxide and prognosis in smokers hospitalised with acute cardiac events: a multicentre, prospective cohort study.

Background: Smoking cigarettes produces carbon monoxide (CO), which can reduce the oxygen-carrying capacity of the blood. We aimed to determine whether elevated expiratory CO levels would be associated with a worse prognosis in smokers presenting with acute cardiac events. Methods: From 7 to 22 April 2021, expiratory CO levels were measured in a prospective registry including all consecutive patients admitted for acute cardiac event in 39 centres throughout France. The primary outcome was 1-year all-cause death. Initial in-hospital major adverse cardiac events (MAE; death, resuscitated cardiac arrest and cardiogenic shock) were also analysed. The study was registered at ClinicalTrials.gov (NCT05063097). Findings: Among 1379 patients (63 ± 15 years, 70% men), 368 (27%) were active smokers. Expiratory CO levels were significantly raised in active smokers compared to non-smokers. A CO level >11 parts per million (ppm) found in 94 (25.5%) smokers was associated with a significant increase in death (14.9% for CO > 11 ppm vs. 2.9% for CO ≤ 11 ppm; p < 0.001). Similar results were found after adjustment for comorbidities (hazard ratio [HR] [95% confidence interval (CI)]): 5.92 [2.43-14.38]) or parameters of in-hospital severity (HR 6.09, 95% CI [2.51-14.80]) and propensity score matching (HR 7.46, 95% CI [1.70-32.8]). CO > 11 ppm was associated with a significant increase in MAE in smokers during initial hospitalisation after adjustment for comorbidities (odds ratio [OR] 15.75, 95% CI [5.56-44.60]) or parameters of in-hospital severity (OR 10.67, 95% CI [4.06-28.04]). In the overall population, CO > 11 ppm but not smoking was associated with an increased rate of all-cause death (HR 4.03, 95% CI [2.33-6.98] and 1.66 [0.96-2.85] respectively). Interpretation: Elevated CO level is independently associated with a 6-fold increase in 1-year death and 10-fold in-hospital MAE in smokers hospitalized for acute cardiac events. Funding: Grant from Fondation Coeur & Recherche.

Characteristics, management, and mid-term prognosis of older adults with cardiogenic shock admitted to intensive care units: Insights from the FRENSHOCK registry.

BACKGROUND: The incidence of heart failure and cardiogenic shock (CS) in older adults is continually increasing due to population aging. To date, prospective data detailing the specific characteristics, management and outcomes of CS in this population are scarce. METHODS: FRENSHOCK is a prospective registry including 772 CS patients from 49 centers. We studied 1-month and 1-year mortality among patients over 75-year-old, adjusted for independent predictors of 1-month and 1-year mortalities. RESULTS: Out of 772 patients included, 236 (30.6%) were 75 years old or more (mean age 81.9 ± 4.7 years, 63.6% male). Compared to patients <75 years old, older adults had a higher prevalence of comorbidities including hypertension, dyslipidemia, chronic kidney disease, and history of heart disease. Older adults were characterized by a lower blood pressure, as well as higher creatinine and lower haemoglobin levels at presentation. Yet, they were less likely to be treated with norepinephrine, epinephrine, invasive ventilation, and renal replacement therapy. They showed a higher 1-month (aHR: 2.5 [1.86-3.35], p < 0.01) and 1-year mortality (aHR: 2.01 [1.58-2.56], p < 0.01). Analysis of both 1-month and 1-year mortality stratified by age quartiles showed a gradual relationship between aging and mortality in CS patients. CONCLUSION: A third of patient with CS in critical care unit are older than 75 years and their risk of death at one month and one year is more than double compared to the younger ones. Further research is essential to identify best therapeutic strategy in this population. NCT02703038.

Beta-blocker management in patients admitted for acute heart failure and reduced ejection fraction: a review and expert consensus opinion.

The role of the beta-adrenergic signaling pathway in heart failure (HF) is pivotal. Early blockade of this pathway with beta-blocker (BB) therapy is recommended as the first-line medication for patients with HF and reduced ejection fraction (HFrEF). Conversely, in patients with severe acute HF (AHF), including those with resolved cardiogenic shock (CS), BB initiation can be hazardous. There are very few data on the management of BB in these situations. The present expert consensus aims to review all published data on the use of BB in patients with severe decompensated AHF, with or without hemodynamic compromise, and proposes an expert-recommended practical algorithm for the prescription and monitoring of BB therapy in critical settings.

Beta Blockers Improve Prognosis When Used Early in Patients with Cardiogenic Shock: An Analysis of the FRENSHOCK Multicenter Prospective Registry.

BACKGROUND: Beta blockers (BBs) are a cornerstone for patients with heart failure (HF) and ventricular dysfunction. However, their use in patients recovering from a cardiogenic shock (CS) remains a bone of contention, especially regarding whether and when to reintroduce this class of drugs. METHODS: FRENSHOCK is a prospective multicenter registry including 772 CS patients from 49 centers. Our aim was to compare outcomes (1-month and 1-year all-cause mortality) between CS patients taking and those not taking BBs in three scenarios: (1) at 24 h after CS; (2) patients who did or did not discontinue BBs within 24 h; and (3) patients who did or did not undergo the early introduction of BBs. RESULTS: Among the 693 CS included, at 24 h after the CS event, 95 patients (13.7%) were taking BB, while 598 (86.3%) were not. Between the groups, there were no differences in terms of major comorbidities or initial CS triggers. Patients receiving BBs at 24 h presented a trend toward reduced all-cause mortality both at 1 month (aHR = 0.61, 95% CI 0.34 to 1.1, p = 0.10) and 1 year, which was, in both cases, not significant. Compared with patients who discontinued BBs at 24 h, patients who did not discontinue BBs showed lower 1-month mortality (aHR = 0.43, 95% CI 0.2 to 0.92, p = 0.03) and a trend to lower 1-year mortality. No reduction in outcomes was observed in patients who underwent an early introduction of BB therapy. CONCLUSIONS: BBs are drugs of first choice in patients with HF and should also be considered early in patients with CS. In contrast, the discontinuation of BB therapy resulted in increased 1-month all-cause mortality and a trend toward increased 1-year all-cause mortality.

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.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Impella for the Management of Ventricular Septal Defect Complicating Acute Myocardial Infarction: A European Multicenter Registry.

Ventricular septal defect (VSD) is a rare but severe complication of myocardial infarction (MI). Temporary mechanical circulatory support (MCS) can be used as a bridge to VSD closure, heart transplantation, or ventricular assist device. We describe the use of Impella device in this context based on a multicenter European retrospective registry (17 centers responded). Twenty-eight post-MI VSD patients were included (Impella device were 2.5 for 1 patient, CP for 20, 5.0 for 5, and unknown for 2). All patients were in cardiogenic shock with multiple organ failure (SAPS II 41 [interquantile range {IQR} = 27-53], lactate 4.0 ± 3.5 mmol/L) and catecholamine support (dobutamine 55% and norepinephrine 96%). Additional temporary MCS was used in 14 patients (50%), mainly extracorporeal life support (ECLS) (n = 9, 32%). Severe bleedings were frequent (50%). In-hospital and 1 year mortalities were 75%. Ventricular septal defect management was surgical for 36% of patients, percutaneous for 21%, and conservative for 43%. Only surgically managed patients survived (70% in-hospital survival). Type and combination of temporary MCS used were not associated with mortality (Impella alone or in combination with intra-aortic balloon pump [IABP] or ECLS, p = 0.84). Impella use in patients with post-MI VSD is feasible but larger prospective registries are necessary to further elucidate potential benefits of left ventricular unloading in this setting.