Selection and Interpretation of Molecular Diagnostics in Heart Transplantation.

The number of heart transplants performed annually in the United States and worldwide continues to increase, but there has been little change in graft longevity and patient survival over the past 2 decades. The reference standard for diagnosis of acute cellular and antibody-mediated rejection includes histologic and immunofluorescence evaluation of endomyocardial biopsy samples, despite invasiveness and high interrater variability for grading histologic rejection. Circulating biomarkers and molecular diagnostics have shown substantial predictive value in rejection monitoring, and emerging data support their use in diagnosing other posttransplant complications. The use of genomic (cell-free DNA), transcriptomic (mRNA and microRNA profiling), and proteomic (protein expression quantitation) methodologies in diagnosis of these posttransplant outcomes has been evaluated with varying levels of evidence. In parallel, growing knowledge about the genetically mediated immune response leading to rejection (immunogenetics) has enhanced understanding of antibody-mediated rejection, associated graft dysfunction, and death. Antibodies to donor human leukocyte antigens and the technology available to evaluate these antibodies continues to evolve. This review aims to provide an overview of biomarker and immunologic tests used to diagnose posttransplant complications. This includes a discussion of pediatric heart transplantation and the disparate rates of rejection and death experienced by Black patients receiving a heart transplant. This review describes diagnostic modalities that are available and used after transplant and the landscape of future investigations needed to enhance patient outcomes after heart transplantation.

Revisiting Biomarkers of Cardiac Allograft Vasculopathy: Addressing the Achilles Heel of Heart Transplantation.

Nearly half of heart transplant recipients will be diagnosed with cardiac allograft vasculopathy (CAV) within five years after transplantation. Advanced CAV can lead to worsening heart failure as well as arrhythmias and sudden cardiac death. The only curative therapy for end-stage CAV is re-transplantation. Current diagnostic methods are invasive and limited by poor sensitivity in early disease. Despite its high prevalence in the post-transplantpopulation, the underlying pathophysiology of this condition has yet to be fully described. It is thought to be primarily related to endothelial dysfunction, immune activation, and cardiometabolic disease. Biomarkers reflecting these underlying processes, particularly endothelial injury and immune activation, have shown early promise in discriminating prevalent CAV. Next-generation sequencing technologies such as proteomic and transcriptomic profiling have also provided further insight into the pathophysiology of CAV through the identification of novel biomarkers. Ultimately, these biomarkers may have a role in not only diagnosing CAV but also highlighting potential targets for disease-specific therapies. In this article, we review the current data for biomarkers in CAV and discuss future directions for biomarker identification..

Cardiogenic Shock: Focus on Non-Cardiac Biomarkers.

PURPOSE OF REVIEW: To examine the evolving multifaceted nature of cardiogenic shock (CS) in the context of non-cardiac biomarkers that may improve CS management and risk stratification. RECENT FINDINGS: There are increasing data highlighting the role of lactate, glucose, and other markers of inflammation and end-organ dysfunction in CS. These biomarkers provide a more comprehensive understanding of the concurrent hemo-metabolic and cellular disturbances observed in CS and offer insights beyond standard structural and functional cardiac assessments. Non-cardiac biomarkers both refine the diagnostic accuracy and improve the prognostic assessments in CS. Further studies revolving around novel biomarkers are warranted to support more targeted and effective therapeutic and management interventions in these high-risk patients.

Beyond Stage C: Considerations in the Management of Patients With Heart Failure Progression and Gaps in Evidence.

Despite treatment with contemporary medical therapies for chronic heart failure (HF), there has been an increase in the prevalence of patients progressing to more advanced disease. Patients progressing to and living at the interface of severe stage C and stage D HF are underrepresented in clinical trials, and there is a lack of high-quality evidence to guide clinical decision making. For patients with severe HF phenotypes, the medical therapies used for patients with less advanced stages of illness are often no longer tolerated or provide inadequate clinical stability. The limited data on these patients highlights the need to increase formal research characterizing this high-risk population. This review summarizes existing clinical trial data and incorporates our considerations for approaches to the medical management of patients advanced "beyond stage C" HF.

Improved Outcomes in Severe Primary Graft Dysfunction After Heart Transplantation Following Donation After Circulatory Death Compared With Donation After Brain Death.

BACKGROUND: Primary graft dysfunction (PGD), the leading cause of early mortality after heart transplantation, is more common following donation after circulatory death (DCD) than donation after brain death (DBD). We conducted a single-center, retrospective cohort study to compare the incidence, severity and outcomes of patients experiencing PGD after DCD compared to DBD heart transplantation. METHODS AND RESULTS: Medical records were reviewed for all adult heart transplant recipients at our institution between March 2016 and December 2021. PGD was diagnosed within 24 hours after transplant according to modified International Society for Heart and Lung Transplant criteria. A total of 459 patients underwent isolated heart transplantation during the study period, 65 (14%) following DCD and 394 (86%) following DBD. The incidence of moderate or severe PGD in DCD and DBD recipients was 34% and 23%, respectively (P = 0.070). DCD recipients were more likely to experience severe biventricular PGD than DBD recipients (19% vs 7.4%; P = 0.004). Among patients with severe PGD, DCD recipients experienced shorter median (Q1, Q3) duration of post-transplant mechanical circulatory support (6 [4, 7] vs 9 [5, 14] days; P = 0.039), shorter median post-transplant hospital length of stay (17 [15, 29] vs 52 [26, 83] days; P = 0.004), and similar 60-day survival rates (100% [95% CI: 76.8%-100%] vs 80.0% [63.1%-91.6%]; P = 0.17) and overall survival (log-rank; P = 0.078) compared with DBD recipients. CONCLUSIONS: DCD heart transplant recipients were more likely to experience severe, biventricular PGD than DBD recipients. Despite this, DCD recipients with severe PGD spent fewer days on mechanical circulatory support and in the hospital than similar DBD patients. These findings suggest that patterns of graft dysfunction and recovery may differ between donor types, and they support the expansion of the heart-donor pool with DCD.

Donation after circulatory determination of death in heart transplant: impact on current and future allocation policy.

PURPOSE OF REVIEW: Historically, the selection criteria for heart transplant candidates has prioritized posttransplant survival while contemporary allocation policy is focused on improving waitlist survival. Donor scarcity has continued to be the major influence on transplant allocation policy. This review will address the opportunity of donation after circulatory determination of death (DCDD) and potential impact on future policy revisions. RECENT FINDINGS: In 2018, changes to U.S. heart allocation policy led to several intended and unintended consequences. Beneficial changes include reduced waitlist mortality and broader geographic sharing. Additional impacts include scarcer pathways to transplant for patients with a durable left ventricular assist device, increased reliance on status exceptions, and expanded use of temporary mechanical support. DCDD is anticipated to increase national heart transplant volumes by ∼30% and will impact waitlist management. Centers that offer DCDD procurement will have reduced waitlist times, reduced waitlist mortality, and higher transplant volumes. SUMMARY: While DCDD will provide more transplant opportunities, donor organ scarcity will persist and influence allocation policies. Differential patient selection, waitlist strategy, and outcome expectations may indicate that allocation is adjusted based on the procurement options at individual centers. Future policy, which will consider posttransplant outcomes, may reflect that different procurement strategies may yield different outcomes.

Towards Allograft Longevity: Leveraging Omics Technologies to Improve Heart Transplant Outcomes.

PURPOSE OF REVIEW: Heart transplantation (HT) remains the optimal therapy for patients living with end-stage heart disease. Despite recent improvements in peri-transplant management, the median survival after HT has remained relatively static, and complications of HT, including infection, rejection, and allograft dysfunction, continue to impact quality of life and long-term survival. RECENT FINDINGS: Omics technologies are becoming increasingly accessible and can identify novel biomarkers for, and reveal the underlying biology of, several disease states. While some technologies, such as gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA), are routinely used in the clinical care of HT recipients, a number of emerging platforms, including pharmacogenomics, proteomics, and metabolomics, hold great potential for identifying biomarkers to aid in the diagnosis and management of post-transplant complications. Omics-based assays can improve patient and allograft longevity by facilitating a personalized and precision approach to post-HT care. The following article is a contemporary review of the current and future opportunities to leverage omics technologies, including genomics, transcriptomics, proteomics, and metabolomics in the field of HT.

Donation After Circulatory Death in Heart Transplantation: History, Outcomes, Clinical Challenges, and Opportunities to Expand the Donor Pool.

Heart transplantation remains the gold-standard therapy for end-stage heart failure; the expected median survival range is 12-13 years. More than 30,000 heart transplants have been performed globally in the past decade alone. With advances in medical and surgical therapies for heart failure, including durable left ventricular assist devices, an increasing number of patients are living with end-stage disease. Last year alone, more than 2500 patients were added to the heart-transplant waitlist in the United States. Despite recent efforts to expand the donor pool, including an increase in transplantation of hepatitis C-positive and extended-criteria donors, supply continues to fall short of demand. Donation after circulatory death (DCD), defined by irreversible cardiopulmonary arrest rather than donor brain death, is widely used in other solid-organ transplants, including kidney and liver, but has not been widely adopted in heart transplantation. However, resurging interest in DCD donation and the introduction of ex vivo perfusion technology has catalyzed recent clinical trials and the development of DCD heart-transplantation programs. Herein, we review the history of DCD heart transplantation, describe the currently used procurement protocols for it and examine clinical challenges and outcomes of such a procedure.

Increased Opportunities for Transplantation for Women in the New Heart Allocation System.

BACKGROUND: Historically, women have had less access to advanced heart failure therapies, including temporary and permanent mechanical circulatory support and heart transplantation (HT), with worse waitlist and post-transplant survival compared with men. This study evaluated for improvement in sex differences across all phases of HT in the 2018 allocation system. METHODS AND RESULTS: The United Network for Organ Sharing registry was queried to identify adult patients (≥18 years) listed for HT from October 18, 2016, to October 17, 2018 (old allocation), and from October 18, 2018, to October 18, 2020 (new allocation). The outcomes of interest included waitlist survival, pretransplant use of temporary and durable mechanical circulatory support, rates of HT, and post-transplant survival. There were 15,629 patients who were listed for HT and included in this analysis; 7745 (2039 women, 26.3%) in the new and 7875 patients (2074 women, 26.3%) in the old allocation system. When compared with men in the new allocation system, women were more likely to have lower priority United Network for Organ Sharing status at time of transplant, and less likely to be supported by an intra-aortic balloon pump (27.1% vs 32.2%, P < .001), with no difference in the use of venoarterial extracorporeal membrane oxygenation (5.5% vs 6.3%, P = .28). Despite these findings, when transplantation was viewed in the context of risk for death or delisting, the cumulative incidence of transplant within 6 months of listing was higher in women than men in the new allocation system (62.4% vs 54.9%, P < .001) with no differences in post-transplant survival. When comparing women in the old with the new allocation system, the distance traveled for organ procurement was 187.5 ± 207.0 miles vs 272.8 ± 233.7 miles (P < .001). CONCLUSIONS: Although the use of temporary mechanical circulatory support in women remains lower than in men in the new allocation system, more women are being transplanted with comparable waitlist and post-transplant outcomes as men. Broader sharing may be making its greatest impact on improving transplant opportunities for women.

Critically appraising the 2018 United Network for Organ Sharing donor allocation policy: adding life boats or rearranging the deck chairs?

PURPOSE OF REVIEW: Due to the growing mismatch between donor supply and demand as well as unacceptably high transplant waitlist mortality, the heart organ allocation system was revised in October 2018. This review gives an overview of the changes in the new heart organ allocation system and its impact on heart transplant practice and outcomes in the United States. RECENT FINDINGS: The 2018 heart allocation system offers a 6-tiered policy and therefore prioritizes the sickest patients on the transplant waitlist. Patients supported with temporary mechanical circulatory support devices are prioritized as Status 1 or Status 2, resulting in increased utilization of this strategy. Patients supported with durable left ventricular assist devices have been prioritized as Status 3 or 4, which has resulted in decreased utilization of this strategy. Broader geographic sharing in the new heart allocation system has resulted in prolonged donor ischemic times. Overall, the new heart allocation system has resulted in significantly lower candidate waitlist mortality, shorter waitlist times, and higher incidence of transplantation. SUMMARY: The new United Network for Organ Sharing allocation policy confers significant advantages over the prior algorithm, allowing for decreased waitlist times and improved waitlist mortality without major impact on posttransplant survival.

Cardiovascular risk stratification in the noncardiac solid organ transplant candidate.

PURPOSE OF REVIEW: Solid organ transplantation (SOT) has become a widely accepted therapy for end-stage disease across the spectrum of thoracic and abdominal organs. With contemporary advances in medical and surgical therapies in transplantation, candidates for SOT are increasingly older with a larger burden of comorbidities, including cardiovascular disease (CVD). CVD, in particular, is a leading cause of morbidity and mortality in SOT candidates with end-stage disease of noncardiac organs [1]. RECENT FINDINGS: Identification of coronary artery disease (CAD), heart failure, and valvular disease are important in noncardiac SOT to ensure both appropriate peri-transplant management and equitable organ allocation. Although the American College of Cardiology (ACC) and the American Heart Association (AHA) have published guidelines and recommendations for the perioperative cardiovascular evaluation of patients undergoing noncardiac surgery, the implications of both symptomatic and asymptomatic CVD differ in patients with end-stage organ failure being considered for SOT when compared to the general population. SUMMARY: Herein, we review the epidemiology, diagnosis, and evidence for the management of CVD in kidney and liver transplantation, combining current guidelines from the 2012 ACC/AHA scientific statement on cardiac disease evaluation in SOT with more contemporary evidenced-based algorithms.

Advanced heart failure patients supported with ambulatory inotropic therapy: What defines success of therapy?

OBJECTIVE: The objective of this study was to describe the profiles and outcomes of a cohort of advanced heart failure patients on ambulatory inotropic therapy (AIT). BACKGROUND: With the growing burden of patients with end-stage heart failure, AIT is an increasingly common short or long-term option, for use as bridge to heart transplant (BTT), bridge to ventricular assist device (BTVAD), bridge to decision regarding advanced therapies (BTD) or as palliative care. AIT may be preferred by some patients and physicians to facilitate hospital discharge. However, counseling patients on risks and benefits is critically important in the modern era of defibrillators, durable mechanical support and palliative care. METHODS: We retrospectively studied a cohort of 241 patients on AIT. End points included transplant, VAD implantation, weaning of inotropes, or death. The primary outcomes were survival on AIT and ability to reach intended goal if planned as BTT or BTVAD. We also evaluated recurrent heart failure hospitalizations, incidence of ventricular arrhythmias (VT/VF) and indwelling line infections. Unintended consequences of AIT, such reaching unintended end point (e.g. VAD implantation in BTT patient) or worse than expected outcome after LVAD or HT, were recorded. RESULTS: Mean age of the cohort was 60.7 ± 13.2 years, 71% male, with Class III-IV heart failure (56% non-ischemic). Average ejection fraction was 19.4 ± 10.2%, pre-AIT cardiac index was 1.5 ± 0.4 L/min/m2 and 24% had prior ventricular arrhythmias. Overall on-AIT 1-year survival was 83%. Hospitalizations occurred in 51.9% (125) of patients a total of 174 times for worsening heart failure, line complication or ventricular arrhythmia. In the BTT cohort, only 42% were transplanted by the end of follow-up, with a 14.8% risk of death or delisting for clinical deterioration. For the patients who were transplanted, 1-year post HT survival was 96.7%. In the BTVAD cohort, 1-year survival after LVAD was 90%, but with 61.7% of patients undergoing LVAD as INTERMACS 1-2. In the palliative care cohort, only 24.5% of patients had a formal palliative care consult prior to AIT. CONCLUSIONS: AIT is a strategy to discharge advanced heart failure patients from the hospital. It may be useful as bridge to transplant or ventricular assist device, but may be limited by complications such as hospitalizations, infections, and ventricular arrhythmias. Of particular note, it appears more challenging to bridge to transplant on AIT in the new allocation system. It is important to clarify the goals of AIT therapy upfront and continue to counsel patients on risks and benefits of the therapy itself and potential unintended consequences. Formalized, multi-disciplinary care planning is essential to clearly define individualized patient, as well as programmatic goals of AIT.

Circulating long chain acylcarnitines and outcomes in diabetic heart failure: an HF-ACTION clinical trial substudy.

BACKGROUND: Whether differences in circulating long chain acylcarnitines (LCAC) are seen in heart failure (HF) patients with and without diabetes mellitus (DM), and whether these biomarkers report on exercise capacity and clinical outcomes, remains unknown. The objective of the current study was to use metabolomic profiling to identify biomarkers that report on exercise capacity, clinical outcomes, and differential response to exercise in HF patients with and without DM. METHODS: Targeted mass spectrometry was used to quantify metabolites in plasma from participants in the heart failure: a controlled trial investigating outcomes of exercise training (HF-ACTION) trial. Principal components analysis was used to identify 12 uncorrelated factors. The association between metabolite factors, diabetes status, exercise capacity, and time to the primary clinical outcome of all-cause mortality or all-cause hospitalization was assessed. RESULTS: A total of 664 participants were included: 359 (54%) with DM. LCAC factor levels were associated with baseline exercise capacity as measured by peak oxygen consumption (beta 0.86, p = 2 × 10-7, and were differentially associated in participants with and without DM (beta 1.58, p = 8 × 10-8 vs. 0.67, p = 9 × 10-4, respectively; p value for interaction = 0.012). LCAC levels changed to a lesser extent in participants with DM after exercise (mean ∆ 0.09, p = 0.24) than in those without DM (mean ∆ 0.16, p = 0.08). In univariate and multivariate modeling, LCAC factor levels were associated with time to the primary outcome (multivariate HR 0.80, p = 2.74 × 10-8), and were more strongly linked to outcomes in diabetic participants (HR 0.64, p = 3.21 × 10-9 v. HR 0.90, p = 0.104, p value for interaction = 0.001). When analysis was performed at the level of individual metabolites, C16, C16:1, C18, and C18:1 had the greatest associations with both exercise capacity and outcomes, with higher levels associated with worse outcomes. Similar associations with time to the primary clinical outcome were not found in a control group of patients without HF from the CATHeterization GENetics (CATHGEN) study. CONCLUSIONS: LCAC biomarkers are associated with exercise status and clinical outcomes differentially in HF patients with and without DM. Impaired fatty acid substrate utilization and mitochondrial dysfunction both at the level of the skeletal muscle and the myocardium may explain the decreased exercise capacity, attenuated response to exercise training, and poor clinical outcomes seen in patients with HF and DM. Trial Registration clinicaltrials.gov Identifier: NCT00047437.

Impact of Bridge to Transplantation With Continuous-Flow Left Ventricular Assist Devices on Posttransplantation Mortality.

BACKGROUND: Bridge to transplantation (BTT) with left ventricular assist devices (LVADs) is a mainstay of therapy for heart failure in patients awaiting heart transplantation (HT). Criteria for HT listing do not differ between patients medically managed and those mechanically bridged to HT. The objectives of the present study were to evaluate the impact of BTT with LVAD on posttransplantation survival, to describe differences in causes of 1-year mortality in medically and mechanically bridged patients, and to evaluate differences in risk factors for 1-year mortality between those with and those without LVAD at the time of HT. METHODS: Using the United Network of Organ Sharing database, we identified 5486 adult, single-organ HT recipients transplanted between 2008 and 2015. Patients were propensity matched for likelihood of LVAD at the time of HT. Kaplan-Meier survival estimates were used to assess the impact of BTT on 1- and 5-year mortality. Logistic regression analysis was used to evaluate the odds ratio of 1-year mortality for patients BTT with LVAD compared with those with medical management across clinically significant variables at various thresholds. RESULTS: Early mortality was higher in mechanically bridged patients: 9.5% versus 7.2% mortality at 1 year (P<0.001). BTT patients incurred an increased risk of 1-year mortality with an estimated glomerular filtration rate of 40 to 60 mL·min-1·1.73 m-2 (odds ratio, 1.69; P=0.003) and <40 mL·min-1·1.73 m-2 (odds ratio, 2.16; P=0.005). A similar trend was seen in patients with a body mass index of 25 to 30 kg/m2 (odds ratio, 1.88; P=0.024) and >30 kg/m2 (odds ratio, 2.11; P<0.001). When patients were stratified by BTT status and the presence of risk factors, including age >60 years, estimated glomerular filtration rate <40 mL·min-1·1.73 m-2, and body mass index >30 kg/m2, there were significant differences in 1-year mortality between medium- and high-risk medically and mechanically bridged patients, with 1-year mortality in high-risk BTT patients at 17.6% compared with 10.4% in high-risk medically managed patients. CONCLUSIONS: Bridge to HT with LVAD, although necessary because of organ scarcity and capable of improving wait list survival, confers a significantly higher risk of early posttransplantation mortality. Patients bridged with mechanical support may require more careful consideration for transplant eligibility after LVAD placement.

Potential for donation after circulatory death heart transplantation in the United States: Retrospective analysis of a limited UNOS dataset.

Donation after Circulatory Death (DCD) is an alternative to Donation after Brain death (DBD), and is a growing strategy for organ procurement in the United States(US). The purpose of this analysis was to review the number and quality of hearts in one United Network for Organ Sharing (UNOS) Region that were not utilized as a potential consequence of nonheart DCD donation. We retrospectively identified all successful US DCD solid organ donors from 1/2011 to 3/1/2017, defined an ideal heart donor by age and left ventricular ejection fraction (LVEF), and then reviewed the donor charts of unused hearts in New York and Vermont (UNOS Region 9). Of 8302 successful DCD donors across the United States, 5033 (61%) were between 18 and 49 years of age, and 872 had a screening echocardiogram, with 573 (66%) measuring an EF >50%. Of these 573 potential donors, 44 (7.7%) were from Region 9. Detailed donor chart review identified 36 ideal heart donors, 24 (66.7%) with anoxic brain injury. Trends in Region 9 DCD donation increased from 4 unused hearts in 2011, to 13 in 2016. In the context of severe organ scarcity, these data indicate that implementation of DCD heart transplantation in the United States would improve overall donation rates and provide a pathway to utilize these ideal donor hearts.

Impact of Obesity on Ventricular Assist Device Outcomes.

BACKGROUND: Obesity remains a relative contraindication for heart transplantation, and hence, obese patients with advanced heart failure receive ventricular assist devices (VADs) either as a destination or "bridge to weight loss" strategy. However, impact of obesity on clinical outcomes after VAD implantation is largely unknown. We sought to determine the clinical outcomes of obese patients with body mass index (BMI) ≥ 35 kg/m2) following contemporary VAD implantation. METHODS: The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry was queried for patients who underwent VAD implantation. Patients were categorized into BMI groups based on World Health Organization classification. RESULTS: Of 17,095 patients, 2620 (15%) had a BMI ≥ 35 kg/m2. Obese patients were likely to be young, non-white, females with dilated cardiomyopathy and undergo device implantation as destination. Survival was similar amongst BMI groups (P = .058). Obese patients had significantly higher risk for infection (hazard ratio [HR]: 1.215; P = .001), device malfunction or thrombosis (HR: 1.323; P ≤ .001), cardiac arrhythmia (HR: 1.188; P = .001) and hospital readmissions (HR: 1.073; P = .022), but lower risk of bleeding (HR: 0.906; P = .018). Significant weight loss (≥10%) during VAD support was achieved only by a small proportion (18.6%) of patients with BMI ≥ 35 kg/m2. Significant weight loss rates observed in obese patients with VAD implantation as destination and bridge to transplant strategy were comparable. Obese patients with significant weight loss were more likely to undergo cardiac transplantation. Weight loss worsened bleeding risk without altering risk for infection, cardiac arrhythmia, and device complications. CONCLUSIONS: Obesity alone should not be considered a contraindication for VAD therapy in contemporary era. Given durability of heart transplantation, strategies should be developed to promote weight loss, which occurs infrequently in obese patients. Impact of weight loss on clinical outcome of obese patients warrants further investigation.

Management of primary graft failure after heart transplantation: Preoperative risks, perioperative events, and postoperative decisions.

Primary graft failure (PGF) after heart transplantation (HT) is a devastating and unexpected event characterized by failure of the graft to adequately support recipient circulation necessitating high doses of vasopressors and inotropes and/or temporary mechanical circulatory support. Although it represents an increasingly common event in the current era, there remains a high degree of variability in prevalence, reported risk factors, and approach to this clinical entity. The purpose of the current review is to highlight preoperative considerations including known incidence and risk factors, perioperative issues involving the identification and management of PGF, and postoperative decisions related to weaning of mechanical circulatory support and titration of immunosuppressive therapy. Lastly, we highlight future directions in PGF research, involving basic and translational research, that have the potential to uncover novel strategies of risk stratification and treatment. CASE: Our patient is a 53-year-old man with end-stage non-ischemic dilated cardiomyopathy complicated by ventricular tachycardia (VT), post-capillary pulmonary hypertension, and renal insufficiency. After progressing to NYHA Class IV symptoms, he underwent implantation of a durable left ventricular assist device (LVAD) as bridge to transplant (BTT). On device support, he developed recurrent VT resulting in multiple defibrillator discharges and hospital admission for intravenous anti-arrhythmic therapy. He is subsequently upgraded to a higher status on the waiting list. A suitable donor is identified, with an appropriate predicted heart mass and an anticipated ischemic time of <4 hours. He is taken to the operating room, where at the time of anesthesia induction he develops vasodilatory shock, requiring high-dose vasopressors, and cardiopulmonary bypass (CPB) support for dissection. After surgical anastomosis, cross clamp removal and reperfusion, graft function is extremely poor, there is significant bradycardia requiring pacing, and the patient is unable to be weaned successfully from CPB. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is initiated, and the patient is transferred to the intensive care unit. Retrospective flow crossmatch is negative. This patient is suffering from severe primary graft failure.

Prognostic Impact of Pulmonary Artery Pulsatility Index (PAPi) in Patients With Advanced Heart Failure: Insights From the ESCAPE Trial.

BACKGROUND: The pulmonary artery pulsatility index (PAPi), defined as the ratio of pulmonary artery pulse pressure to right atrial pressure, emerged as a powerful predictor of right ventricular (RV) failure in patients with acute inferior myocardial infarction and those undergoing left ventricular assist device placement; however, its prognostic utility in the advanced heart failure population remains largely unknown. METHODS AND RESULTS: We comparatively analyzed PAPi with traditional indices of RV function including RV stroke work index and right atrial/pulmonary capillary wedge pressure ratio (RAP/PCWP) in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial. Median PAPi score was 2.35 in 190 patients. PAPi was significantly associated with clinical (jugular venous distention, ascites, edema), echocardiographic (right atrial size, vena cava size, tricuspid regurgitation velocity), and hemodynamic signs of RV failure (RAP, PCWP); all P < .05. In addition, PAPi was associated with the measures of left ventricular function, including ejection fraction, cardiac index, and PCWP (all P < .05). In Cox regression analysis, PAPi was an independent predictor of primary endpoint of death or hospitalization at 6 months (hazard ratio 0.91 [95% confidence interval 0.84-0.99], P = .022), whereas RA pressure, RV stroke work index, or RA/PCWP were not. CONCLUSIONS: PAPi serves as a marker of RV dysfunction and strongly predicts adverse clinical events in patients with advanced heart failure. Incorporating PAPi into existing risk models can substantially improve patient selection for advanced therapies and clinical outcomes in this population.

VA-ECMO for cardiogenic shock in the contemporary era of heart transplantation: Which patients should be urgently transplanted?

With the impending United Network for Organ Sharing (UNOS) heart allocation policy giving VA-ECMO supported heart transplant (HT) candidates highest priority status (Tier 1), identifying patients in cardiogenic shock (CS) with severe and irreversible heart failure (HF) appropriate for urgent HT is critically important. In a center where wait times currently preclude this approach, we retrospectively reviewed 119 patients (ages 18-72) with CS from 1/2014 to 12/2016 who required VA-ECMO for >24 hours. Underlying aetiologies included postcardiotomy shock (45), acute coronary syndromes (33), and acute-on-chronic HF (16). Eighty-four percent of patients (100) had ≥1 contraindication to HT with 61.3% (73) having preexisting contraindications (eg, multiorgan dysfunction and substance abuse), and 68.1% (81) experienced preclusive complications (eg, renal failure, coagulopathy, and infection). Potential HT candidates were significantly more likely to survive to discharge (potential HT candidates 84.2% vs preexisting contraindications 43.8% vs contraindications developing on VA-ECMO 33.3%, P = 0.001). Among potential HT candidates, 11 (68.8%) were discharged without advanced therapies and 4 received durable left ventricular assist device (25.0%). Importantly, 1-year survival was 100% for the 11 patients with follow-up. Thus, further work is critical to define appropriate candidates for HT from VA-ECMO while avoiding preemptive transplantation in those with otherwise favorable outcomes.