Extracorporeal Membrane Oxygenation for Graft Dysfunction Early After Heart Transplantation: A Systematic Review and Meta-analysis.

INTRODUCTION: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO. METHODS AND RESULTS: We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%-39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%-57%). Recipient age (odds ratio 1.02, 95% CI 1.01-1.04) and prior sternotomy (OR 1.57, 95% CI 0.99-2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death. CONCLUSIONS: One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT.

The role of surgery for secondary mitral regurgitation and heart failure in the era of transcatheter mitral valve therapies.

The approach to the management of mitral valve (MV) disease and heart failure (HF) has dramatically changed over the last decades. It is well recognized that severe mitral regurgitation secondary to ischemic or non-ischemic cardiomyopathy is associated with an excess risk of mortality. Understanding the impact of the surgical treatment modality on mortality outcomes has been difficult due to the broad spectrum of secondary mitral regurgitation (SMR) phenotypes and lack of randomized surgical clinical trials. Over the last 30 years, surgeons have failed to provide compelling evidence to convince the medical community of the need to treat SMR in patients with severe HF. Therefore, the surgical treatment of SMR has never gained uniform acceptance as a significant option among patients suffering from SMR. Recent evidence from randomized trials in a non-surgical eligible patients treated with transcatheter therapies, has provided a new perspective on SMR treatment. Recently published European and American guidelines confirm the key role of percutaneous treatment of SMR and in parallel, these guidelines reinforce the role of mitral valve surgery in patients who require surgical revascularization. Complex mitral valve repair combining subvalvular apparatus repair along with annuloplasty seems to be a promising approach in selected patients in selected centers. Meanwhile, mitral valve replacement has become the preferred surgical strategy in most patients with advanced heart failure and severe LV remodeling or high risk of recurrent mitral regurgitation. In this comprehensive review, we aimed to discuss the role of mitral surgery for SMR in patients with heart failure in the contemporary era and to provide a practical approach for its surgical management.

Parameters associated with successful weaning of veno-arterial extracorporeal membrane oxygenation: a systematic review.

PURPOSE: Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) can be used to restore organ perfusion in patients with cardiogenic shock until native heart recovery occurs. It may be challenging, however, to determine when patients can be weaned successfully from ECMO-surviving without requiring further mechanical support or heart transplant. We aimed to systematically review the medical literature to determine the biomarkers, hemodynamic and echocardiographic parameters associated with successful weaning of VA-ECMO in adults with cardiogenic shock and to present an evidence-based weaning algorithm incorporating key findings. METHOD: We systematically searched PubMed, Embase, ProQuest, Google Scholars, Web of Science and the Grey literature for pertinent original research reports. We excluded studies limited to extracorporeal cardiopulmonary resuscitation (ECPR) as the neurological prognosis may significantly alter the decision-making process surrounding the device removal in this patient population. Studies with a mixed population of VA-ECMO for cardiogenic shock or cardiac arrest were included. We excluded studies limited to patients in which ECMO was only used as a bridge to VAD or heart transplant, as such patients are, by definition, never "successfully weaned." We used the Risk of Bias Assessment tool for Non-Randomized Studies. The study was registered on the International prospective register of systematic reviews (PROSPERO CRD42020178641). RESULTS: We screened 14,578 records and included 47 that met our pre-specified criteria. Signs of lower initial severity of shock and myocardial injury, early recovery of systemic perfusion, left and right ventricular recovery, hemodynamic and echocardiographic stability during flow reduction trial and/or pump-controlled retrograde trial off predicted successful weaning. The most widely used parameter was the left ventricular outflow tract velocity time integral, an indicator of stroke volume. Most studies had a moderate or high risk of bias. Heterogeneity in methods, timing, and conditions of measurements precluded any meta-analysis. CONCLUSIONS: In adult patients on VA-ECMO for cardiogenic shock, multiple biomarkers, hemodynamic and echocardiographic parameters may be used to track resolution of systemic hypoperfusion and myocardial recovery in order to identify patients that can be successfully weaned.

Coronary endarterectomy in patients with diffuse coronary artery disease: assessment of graft patency with computed tomography angiography.

BACKGROUND: With a growing population of patients with advanced coronary artery disease (CAD), many of whom have undergone prior percutaneous coronary interventions, coronary endarterectomy (CE) allows for the extension of revascularization in patients with otherwise limited options. Whether adjunctive CE associated with standard surgery, combined with contemporary antiplatelet therapy, improves outcomes remains largely unknown. METHODS: We studied 147 consecutive patients who underwent 154 adjunctive CE procedures for advanced CAD between January 2015 and January 2018. We used computed tomography angiography (CTA) in a subgroup of 32 consecutive patients who underwent CE during coronary artery bypass grafting after June 2016 to assess graft and coronary patency. RESULTS: Patients (mean age 67 ± SD 10 yr) underwent CE of the right (102 patients), the left anterior descending (LAD, 22 patients) and the circumflex (17 patients) coronary arteries. Seven patients (5%) experienced a procedural myocardial infarction and there were no perioperative deaths. Among the 32 patients who underwent CTA 3 months after surgery, the mean patency of the endarterectomized coronary arteries and bypass grafts was 90% and 88%, respectively. All 6 arterial grafts on the LAD artery were patent. The mean survival rate and the mean rate of freedom from major adverse cardiovascular events was 95% ± 2% and 95% ± 6%, respectively. The patency rate was 100 % for patients evaluated at 3-year follow up. CONCLUSION: Coronary endarterectomy offers a surgical option for patients with diffuse CAD who may be unsuitable for coronary bypass alone. Grafts and endarterectomized coronary artery patency remain adequate and explain the excellent patient survival and the freedom rate from major adverse cardiovascular events.

Early and Long-Term Outcomes after Direct Bridge-to-Transplantation with Extracorporeal Membrane Oxygenation.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as direct bridge-to-transplantation (dBTT) remains controversial. We compared the short- and long-term outcomes of adult patients undergoing urgent heart transplantation (HT) with (dBTT) and without (non-BTT) VA-ECMO support at the time of HT. METHODS: Adults who underwent urgent HT in two institutions were assessed (N = 133; dBTT: N = 34 and non-BTT: N = 99). Patient characteristics, donor characteristics, in-hospital outcomes, and overall survival were compared. Mean follow up was 77±38 months and was 100% complete. Mortality predictors were identified using univariate and multivariate analyses. RESULTS: Before HT, patients with dBTT had higher rates of ischemic cardiomyopathy, acute kidney injury, liver failure, respiratory failure, and longer graft ischemia times. More patients in the dBTT group had complications, such as requiring VA-ECMO postoperatively (dBTT=50% vs. non-BTT=20%, P < 0.01). Hospital deaths (dBTT=23% vs. non-BTT=19%, P = 0.58), one-year (74% vs. 80%) and five-year survival (62% vs. 75%, P = 0.74 for overall survival) were not significantly different. The MELD-XI score and previous cardiac surgery were independent predictors of hospital mortality. CONCLUSION: Direct bridge-to-transplantation in patients on VA-ECMO support was not associated with worse long-term outcomes compared with non-VA-ECMO urgent HT, especially in recipients without any associated organ failure and a low MELD-XI score before HT.

Use of extracorporeal membrane oxygenation for heart graft dysfunction in adults: incidence, risk factors and outcomes in a multicentric study.

BACKGROUND: The decision about whether to use venoarterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiac graft dysfunction (GD) is usually made on a case-by-case basis and is guided by the team's experience. We aimed to determine the incidence of VA-ECMO use after heart transplantation (HT), to assess early- and long-term outcomes and to assess risk factors for the need for VA-ECMO and early mortality in these patients. METHODS: We included adults who underwent heart transplantation at 3 cardiac centres who met the most recent International Society for Heart and Lung Transplantation definition of graft dysfunction (GD) over a 10-year period. Pre-transplant, intraoperative and posttransplant characteristics of the heart recipients as well as donor characteristics were analyzed and compared among recipients with GD treated with and without VA-ECMO. RESULTS: There were 135 patients with GD in this study, of whom 66 were treated with VA-ECMO and 69 were not. The mean follow-up averaged 81.2 months (standard deviation 36 mo, range 0-184 mo); follow-up was complete in 100% of patients. The overall incidence of GD (30%) and of VA-ECMO use increased over the study period. We did not identify any predictive pre-transplantation factors for VA-ECMO use, but patients who required VA-ECMO had higher serum lactate levels and higher inotropes doses after HT. The overall survival rates were 83% and 42% at 1 year and 78% and 40% at 5 years among patients who received only medical treatment and those who received VA-ECMO, respectively. Delayed initiation of VA-ECMO and postoperative bleeding were strongly associated with increased in-hospital mortality. CONCLUSION: The incidence of GD increased over the study period, and the need for VA-ECMO among patients with GD remains difficult to predict. In-hospital mortality decreased over time but remained high among patients who required VA-ECMO, especially among patients with delayed initiation of VA-ECMO.

Right ventricular reserve in a piglet model of chronic pulmonary hypertension.

Right ventricular (RV) response to exercise or pharmacological stress is not well documented in pulmonary hypertension (PH). We investigated the relationship between RV reserve and ventricular-arterial coupling. Surgical ligation of the left pulmonary artery was performed in 13 Large White piglets (PH group), thereafter weekly embolisations of the right lower lobe were performed for 5 weeks. A control group of six piglets underwent sham procedures. Right heart catheterisation and echocardiography were performed at week 6. Pressure-volume loops were recorded before and after dobutamine infusion. Induction of experimental PH resulted in a higher mean ± sd pulmonary artery pressure (34 ± 9 versus 14 ± 2 mmHg; p<0.01) and in a lower ventricular-arterial coupling efficiency (0.66 ± 0.18 versus 1.24 ± 0.17; p<0.01) compared with controls at 6 weeks. Dobutamine-induced relative changes in RV stroke volume index (SVI) and end-systolic elastance were lower in the PH group (mean ± SD 47 ± 5% versus 20 ± 5%, p<0.01, and 81 ± 37% versus 32 ± 14%, p<0.01, respectively). Change in SVI was strongly associated with resting ventricular-arterial coupling (R(2)=0.74; p<0.01). RV reserve was associated with ventricular-arterial coupling in a porcine model of chronic pressure overload.

Determinants of survival following heart transplantation in adults with congenital heart disease.

BACKGROUND: Adult patients surviving with congenital heart disease (ACHD) is growing. We examine the factors associated with heart transplant outcomes in this challenging population with complex anatomy requiring redo-surgeries. METHODS: We reviewed the United Network for Organ Sharing-Standard Transplant Analysis and Research database and analyzed 35,952 heart transplants from January 1st, 2000, to September 30th, 2018. We compared transplant characteristics for ischemic cardiomyopathy (ICM) (n = 14,236), nonischemic cardiomyopathy (NICM) (n = 20,676), and ACHD (n = 1040). Mean follow-up was 6.20 ± 4.84 years. Kaplan-Meier survival curves and Cox-proportional hazards analysis were used to analyze survival data. RESULTS: Multivariable analysis confirmed that ACHD was associated greater in-hospital death compared to ICM (HR = 0.54, P < 0.001) and NICM (HR = 0.46, P < 0.001). Notable factors associated with increased mortality were history of cerebrovascular disease (HR = 1.11, P = 0.026), prior history of malignancy (HR = 1.12, P = 0.006), pre-transplant biventricular support (HR = 1.12, P = 0.069), postoperative stroke (HR = 1.47, P < 0.001) and postoperative dialysis (HR = 1.71, P < 0.001). ACHD transplants had a longer donor heart ischemic time (P < 0.001) and trend towards more deaths from primary graft dysfunction (P = 0.07). In-hospital deaths were more likely with ACHD and use of mechanical support such as use of right ventricular assist device (HR = 2.20, P = 0.049), biventricular support (HR = 1.62, P < 0.001) and extracorporeal membrane oxygenation (HR = 2.36, P < 0.001). Conditional survival after censoring hospital deaths was significantly higher in ACHD (P < 0.001). CONCLUSION: Heart transplant in ACHD is associated with a higher post-operative mortality given anatomical complexity but a better long-term conditional survival. Normothermic donor heart perfusion may improve outcomes in the ACHD population by reducing the impact of longer ischemic times.

Experimental models of right heart failure: a window for translational research in pulmonary hypertension.

The right ventricle (RV) faces major changes in loading conditions associated with cardiovascular and pulmonary vascular disorders. Despite major pharmacological advances since the last decade, pulmonary arterial hypertension remains a deadly disease mainly secondary to the development of right ventricular failure (RVF). Several experimental models of RVF have been developed over the past three decades providing a particular insight in RV pathophysiology. Mechanisms involved in the transition from RV adaptive hypertrophy to maladaptive remodeling and failure in conditions of chronic RV pressure or volume overload are of a great interest but not yet completely understood. Further investigations are needed to find new therapeutic approaches for RVF. Current animal models and emerging concepts of translational RV research will be detailed in this review.

Value of CT and 18F-FDG PET/CT Imaging for Preoperative Screening in Advanced Heart Failure Therapy Candidates.

This study assesses the impact of contrast-enhanced chest and abdominal computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT in preoperative screening of heart transplantation or ventricular assist device candidates. Patients who underwent both studies within a 6-month interval at our institution between 2014 and 2021 were reviewed for significant findings, defined as possible contraindications or actionable findings. Among the 79 included patients, significant findings were found in 38 (48.1%) with CT and in 18 (22.8%) with FDG-PET/CT (P = 0.0015). FDG-PET/CT identified 10 additional significant findings, but none of these precluded patient listing for heart transplantation. Use of FDG-PET/CT may lead to unnecessary investigations when performed indiscriminately in all patients.

La présente étude se penche sur l'incidence du recours à une tomodensitométrie (TDM) thoracique et abdominale avec produit de contraste et à une tomographie par émission de positrons au fluorodésoxyglucose marqué au fluor 18 (TEP-18FDG) lors d'évaluation préopératoire de candidats à une transplantation cardiaque ou à l'implantation d'un dispositif d'assistance ventriculaire. Les résultats obtenus de 79 patients qui ont subi ces deux examens dans un intervalle maximal de six mois à notre établissement entre 2014 et 2021 ont été analysés à la recherche de conclusions pertinentes, définies comme des contre-indications possibles à l'intervention ou des résultats ayant un impact direct sur la prise en charge du patient. De telles conclusions ont été constatées chez 38 participants (48,1 %) suite à une TDM et 18 participants (22,8 %) suite à une TEP-18FDG (p = 0,0015). La TEP-18FDG a permis de relever 10 résultats d'importance supplémentaires, mais aucun d'entre eux n'aurait entraîné l'inadmissibilité du patient à une transplantation cardiaque. L'utilisation de la TEP-18FDG pourrait donner lieu à des examens non nécessaires lorsqu'elle est réalisée sans distinction chez tous les patients.

A bridge-to-bridge approach to heart transplantation using extracorporeal membrane oxygenation and total artificial heart.

BACKGROUND: This study aims to describe the outcomes after heart transplantation using a bridge-to-bridge strategy with a sequence of extracorporeal membrane oxygenation (ECMO) support followed by temporary total artificial heart implantation (TAH-t). METHODS: A retrospective, multicenter analysis of 54 patients who underwent TAH-t implantation following an ECMO for cardiogenic shock was performed (ECMO-TAH-t group). A control group of 163 patients who underwent TAH-t implantation as a direct bridge to transplantation (TAH-t group) was used to assess this strategy's impact on outcomes. RESULTS: Fifty-four patients, averaging 47 ± 13 year old, underwent implantation of a TAH-t after 5.3 ± 3.4 days of ECMO perfusion for cardiogenic shock. In the ECMO-TAH-t group, 20 patients (20/54%; 37%) died after TAH-t implantation and 57 patients (57/163%; 35%) died in the TAH-t group (Gray test; P = .49). The top 3 causes of death of patients on TAH-t support were multisystem organ failure (40%), sepsis (20%), and neurologic events (20%). Overall, 32 patients (32/54%; 59%) underwent heart transplantation in the ECMO-TAH-t group compared with 106 patients (106/163%, 65%) in the TAH-t group (P = .44). No significant difference in survival was observed at 6 months, 1 year, and 3 years after heart transplant (ECMO-TAH-t group: 94%, 87%, and 80% vs 87%, 83%, and 76% in the TAH-t group, respectively). Deterioration of liver function (bilirubin, aspartate transaminase, and alanine aminotransferase levels on TAH-t) was associated with increased mortality before heart transplant in both groups. CONCLUSIONS: Sequential bridging from ECMO to TAH-t followed by heart transplantation is a viable option for a group of highly selected patients.

Extracorporeal membrane oxygenation and microaxial left ventricular assist device in cardiogenic shock: Choosing the right mechanical circulatory support to improve outcomes.

Objective: To evaluate the outcomes of patients supported with Impella (CP/5.0) or venoarterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock according to shock phenotype. The primary end point was 30-day survival. Methods: A retrospective study of patients supported with Impella (CP/5.0) or VA-ECMO between 2010 and 2020 was performed. Patients were grouped according to 1 of 2 shock phenotypes: isolated left ventricular (LV) dysfunction versus biventricular dysfunction or multiple organ failure (MOF). The local practice favors Impella for isolated LV dysfunction and VA-ECMO for biventricular dysfunction or MOF. Results: Among the 75 patients included, 17 (23%) had isolated LV dysfunction. Patients with biventricular dysfunction or MOF had a greater median lactate level compared with those with isolated LV dysfunction (7.9 [2.9-11.8] vs 3.8 [1.1-5.8] mmol/L, respectively). Among patients with isolated LV dysfunction, 30-day survival was 46% for the Impella group (n = 13) and 75% for VA-ECMO (n = 4). Among patients with biventricular dysfunction or MOF, 30-day survival was 9% for the Impella group (n = 11) and 28% for VA-ECMO (n = 47). Patients supported with Impella 5.0 had better 30-day survival compared with those supported with Impella CP, for both shock phenotypes (83% vs 14% and 14% vs 0%, respectively). Conclusions: In this small cohort, patients supported with Impella for isolated LV dysfunction and VA-ECMO for biventricular dysfunction or MOF had acceptable survival at 30 days. Patients with biventricular dysfunction or MOF who were supported by Impella had the lowest survival rates. Patients with isolated LV dysfunction who were supported with VA-ECMO had good 30-day survival.

Preoperative passive venous pressure-driven cardiac function determines left ventricular assist device outcomes.

BACKGROUND: Right heart output in heart failure can be compensated through increasing systemic venous pressure. We determined whether the magnitude of this "passive cardiac output" can predict LVAD outcomes. METHODS: This was a retrospective review of 383 patients who received a continuous-flow LVAD at the University of Michigan between 2012 and 2021. Pre-LVAD cardiac output driven by venous pressure was determined by dividing right atrial pressure by mean pulmonary artery pressure, multiplied by total cardiac output. Normalization to body surface area led to the passive cardiac index (PasCI). The Youden J statistic was used to identify the PasCI threshold, which predicted LVAD death by 2 years. RESULTS: Increased preoperative PasCI was associated with reduced survival (hazard ratio [HR], 2.27; P < .01), and increased risk of right ventricular failure (RVF) (HR, 3.46; P = .04). Youden analysis showed that a preoperative PasCI ≥0.5 (n = 226) predicted LVAD death (P = .10). Patients with PasCI ≥0.5 had poorer survival (P = .02), with a trend toward more heart failure readmission days (mean, 45.09 ± 67.64 vs 35.13 ± 45.02 days; P = .084) and increased gastrointestinal bleeding (29.2% vs 20.4%; P = .052). Additionally, of the 97 patients who experienced readmissions for heart failure, those with pre-LVAD implantation PasCI ≥0.5 were more likely to have more than 1 readmission (P = .05). CONCLUSIONS: Although right heart output can be augmented by raising venous pressure, this negatively impacts end-organ function and increases heart failure readmission days. Patients with a pre-LVAD PasCI ≥0.5 have worse post-LVAD survival and increased RVF. Using the PasCI metric in isolation or incorporated into a predictive model may improve the management of LVAD candidates with RV dysfunction.

Association of Days Alive and Out of the Hospital After Ventricular Assist Device Implantation With Adverse Events and Quality of Life.

Importance: There is a need to better assess the cumulative effect on morbidity and mortality in patients undergoing durable left ventricular assist device (LVAD) implantation. This study evaluates a patient-centered performance metric (days alive and out of hospital [DAOH]) for durable LVAD therapy. Objective: To determine the incidence of percent of DAOH before and after LVAD implantation and (2) explore its association with established quality metrics (death, adverse events [AEs], quality of life). Design, Settings, and Participants: This was a retrospective national cohort study of Medicare beneficiaries implanted with a durable continuous-flow LVAD between April 2012 and December 2016. The data were analyzed from December 2021 to May 2022. Follow-up was 100% complete at 1 year. Data from The Society of Thoracic Surgeons Intermacs registry were linked to Medicare claims. Main Outcomes and Measures: The number of DAOH 180 days before and 365 days after LVAD implantation and daily patient location (home, index hospital, nonindex hospital, skilled nursing facility, rehabilitation center, hospice) were calculated. Percent of DAOH was indexed to each beneficiary's pre- (percent DAOH-BF) and postimplantation (percentage of DAOH-AF) follow-up time. The cohort was stratified by terciles of percentage of DAOH-AF. Results: Among the 3387 patients included (median [IQR] age: 66.3 [57.9-70.9] years), 80.9% were male, 33.6% and 37.1% were Interfaces Patient Profile 2 and 3, respectively, and 61.1% received implants as destination therapy. Median (IQR) percent of DAOH-BF was 88.8% (82.7%-93.8%) and 84.6% (62.1-91.5%) for percent of DAOH-AF. While DAOH-BF was not associated with post-LVAD outcomes, patients in the low tercile of percentage of DAOH-AF had a longer index hospitalization stay (mean, 44 days; 95% CI, 16-77), were less likely to be discharged home (mean. -46.4 days; 95% CI, 44.2-49.1), and spent more time in a skilled nursing facility (mean, 27 days; 95% CI, 24-29), rehabilitation center (mean, 10 days; 95% CI, 8-12), or hospice (mean, 6 days; 95% CI, 4-8). Increasing percentage of DAOH-AF was associated with patient risk, AEs, and indices of HRQoL. Patients experiencing non-LVAD-related AEs had the lowest percentage of DAOH-AF. Conclusions and Relevance: Significant variability existed in the percentage of DAOH within a 1-year time horizon and was associated with the cumulative AEs burden. This patient-centered measure may assist clinicians in informing patients about expectations after durable LVAD implantation. Validation of percentage DAOH as a quality metric for LVAD therapy across centers should be explored.

Transcatheter valvular therapies in patients with left ventricular assist devices.

Aortic, mitral and tricuspid valve regurgitation are commonly encountered in patients with continuous-flow left ventricular assist devices (CF-LVADs). These valvular heart conditions either develop prior to CF-LVAD implantation or are induced by the pump itself. They can all have significant detrimental effects on patients' survival and quality of life. With the improved durability of CF-LVADs and the overall rise in their volume of implants, an increasing number of patients will likely require a valvular heart intervention at some point during CF-LVAD therapy. However, these patients are often considered poor reoperative candidates. In this context, percutaneous approaches have emerged as an attractive "off-label" option for this patient population. Recent data show promising results, with high device success rates and rapid symptomatic improvements. However, the occurrence of distinct complications such as device migration, valve thrombosis or hemolysis remain of concern. In this review, we will present the pathophysiology of valvular heart disease in the setting of CF-LVAD support to help us understand the underlying rationale of these potential complications. We will then outline the current recommendations for the management of valvular heart disease in patients with CF-LVAD and discuss their limitations. Lastly, we will summarize the evidence related to transcatheter heart valve interventions in this patient population.

Impact of clinical variables on outcomes in refractory cardiac arrest patients undergoing extracorporeal cardiopulmonary resuscitation.

Background: In the past two decades, extracorporeal resuscitation (ECPR) has been increasingly used in the management of refractory cardiac arrest (CA) patients. Decision algorithms have been used to guide the care such patients, but the effectiveness of such decision-making tools is not well described. The aim of this study was to compare the rate of survival with a good neurologic outcome of patients treated with ECPR meeting all criteria of a clinical decision-making tool for the initiation of ECPR to those for whom ECPR was implemented outside of the algorithm. Methods: All patients who underwent E-CPR between January 2014 and December 2021 at the Montreal Heart Institute were included in this retrospective analysis. We dichotomized the cohort according to adherence or non-adherence with the ECPR decision-making tool, which included the following criteria: age ≤65 years, initial shockable rhythm, no-flow time <5 min, serum lactate <13 mmol/L. Patients were included in the "IN" group when they met all criteria of the decision-making tool and in the "OUT" group when at least one criterion was not met. Main outcomes and measures: The primary outcome was survival with intact neurological status at 30 days, defined by a Cerebral Performance Category (CPC) Scale 1 and 2. Results: A total of 41 patients (IN group, n = 11; OUT group, n = 30) were included. A total of 4 (36%) patients met the primary outcome in the IN group and 7 (23%) in the OUT group [odds ratio (OR): 1.88 (95% CI, 0.42-8.34); P = 0.45]. However, survival with a favorable outcome decreased steadily with 2 or more deviations from the decision-making tool [2 deviations: 1 (11%); 3 deviations: 0 (0%)]. Conclusion and relevance: Most patients supported with ECPR fell outside of the criteria encompassed in a clinical decision-making tool, which highlights the challenge of optimal selection of ECPR candidates. Survival rate with a good neurologic outcome did not differ between the IN and OUT groups. However, survival with favorable outcome decreased steadily after one deviation from the decision-making tool. More studies are needed to help select proper candidates with refractory CA patients for ECPR.

Metabolic reprogramming by immune-responsive gene 1 up-regulation improves donor heart preservation and function.

Preservation quality of donor hearts is a key determinant of transplant success. Preservation duration beyond 4 hours is associated with primary graft dysfunction (PGD). Given transport time constraints, geographical limitations exist for donor-recipient matching, leading to donor heart underutilization. Here, we showed that metabolic reprogramming through up-regulation of the enzyme immune response gene 1 (IRG1) and its product itaconate improved heart function after prolonged preservation. Irg1 transcript induction was achieved by adding the histone deacetylase (HDAC) inhibitor valproic acid (VPA) to a histidine-tryptophan-ketoglutarate solution used for donor heart preservation. VPA increased acetylated H3K27 occupancy at the IRG1 enhancer and IRG1 transcript expression in human donor hearts. IRG1 converts aconitate to itaconate, which has both anti-inflammatory and antioxidant properties. Accordingly, our studies showed that Irg1 transcript up-regulation by VPA treatment increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in mice, which was accompanied by increased antioxidant protein expression [hemeoxygenase 1 (HO1) and superoxide dismutase 1 (SOD1)]. Deletion of Irg1 in mice (Irg1-/-) negated the antioxidant and cardioprotective effects of VPA. Consistent with itaconate's ability to inhibit succinate dehydrogenase, VPA treatment of human hearts increased itaconate availability and reduced succinate accumulation during preservation. VPA similarly increased IRG1 expression in pig donor hearts and improved its function in an ex vivo cardiac perfusion system both at the clinical 4-hour preservation threshold and at 10 hours. These results suggest that augmentation of cardioprotective immune-metabolomic pathways may be a promising therapeutic strategy for improving donor heart function in transplantation.

Assessment of Ex Vivo Murine Biventricular Function in a Langendorff Model.

Primary graft dysfunction (PGD) remains the leading cause of early death following heart transplantation. Prolonged ischemic time during cold preservation is an important risk factor for PGD, and reliable evaluation of cardiac function is essential to study the functional responses of the donor heart after cold preservation. The accompanying video describes a technique to assess murine right and left ventricular function using ex vivo perfusion based in a Langendorff model after cold preservation for different durations. In brief, the heart is isolated and stored in a cold histidine-tryptophan-ketoglutarate (HTK) solution. Then, the heart is perfused with a Kreb buffer in a Langendorff model for 60 min. A silicone balloon is inserted into the left and right ventricle, and cardiac functional parameters are recorded (dP/dt, pressure-volume relationships). This protocol allows the reliable evaluation of cardiac function after different heart preservation protocols. Importantly, this technique allows the study of cardiac preservation responses specifically in native cardiac cells. The use of very small murine hearts allows access to an enormous array of transgenic mice to investigate the mechanisms of PGD.