Publications

Abstract

Extracorporeal membrane oxygenation (ECMO) has emerged as a crucial tool in the care of patients with multiorgan failure, and is increasingly utilized as a bridge to transplantation. While data on ECMO as a bridge to isolated heart and lung transplantation have been described, our emerging experience with ECMO as a bridge to thoracic multiorgan transplantation is not yet well understood. This study aims to investigate temporal trends, utilization, and outcomes in ECMO as a bridge to thoracic multiorgan transplantation.The United Network for Organ Sharing database was used to identify adult patients undergoing thoracic multiorgan transplantation between 1987 and 2022. Exclusion criteria were recipient age <18 and bridging with other mechanical circulatory support including ventricular assist device (VAD) and intra-aortic balloon pump (IABP). Survival analysis was performed to compare outcomes between patients bridged to transplantation with ECMO and those who were not bridged.Of 3,927 patients undergoing thoracic multiorgan transplantation, a total of 203 (5.2%) patients received ECMO as a bridge to transplantation. Among ECMO recipients, patients were most commonly bridged to heart-lung (45.8%), followed by heart-kidney (34.5%), and lung-kidney transplantation (11.8%). At a median follow-up of 35.5 months, unadjusted survival among patients bridged with ECMO was decreased versus multiorgan transplant recipients who were not bridged (p<0.001). With adjusted multivariable Cox regression, ECMO was independently associated with an elevated risk of mortality following multiorgan transplantation (HR 1.56 [1.21-2.02], p<0.01). Among patients surviving past 30 days following transplantation, conditional long-term survival was similar between those bridged with ECMO and those not bridged (p = 0.82).ECMO is increasingly utilized as a bridge to thoracic multiorgan transplantation, and is associated with increased 30 day mortality and decreased long-term survival. In select patients surviving to 30 days following transplantation, similar long-term survival is seen between patients bridged with ECMO and those not bridged.

View details for DOI 10.1016/j.healun.2024.09.015

View details for PubMedID 39343333

Abstract

Combined heart-liver transplantation (CHLT) is a definitive therapy reserved for patients with concomitant heart failure and advanced liver disease. A limited number of centers perform CHLT, and even fewer use the en bloc implantation technique. This study 1) reviews clinical outcomes and immunoprotective effects following CHLT, and 2) describes our institution's experience of over two decades using the en bloc technique.All patients who underwent CHLT at our institution between January 2003 and July 2023 were identified. Recipient and donor characteristics, operative details, and clinical outcomes were assessed. Kaplan-Meier analysis was performed to evaluate survival following CHLT.A total of 20 patients underwent CHLT using the en bloc technique at our institution between January 2003 and July 2023. At a median follow-up of 3.8 years for patients who survived the perioperative period (n=18), estimated survival at 1- and 5-years was 94% and 75%, respectively. There was 100% freedom from acute moderate rejection, acute severe rejection, and chronic rejection in all patients. No patients required re-transplantation due to rejection.CHLT is a definitive therapy reserved for patients with multi-organ dysfunction. At our institution, the en bloc technique is the preferred operative approach, as it minimizes cardiac insult, requires fewer anastomoses, minimizes cold ischemia time, and allows for rapid correction of coagulopathy. Overall survival for this cohort is excellent. Episodes of acute rejection were rarely observed, providing further support that the liver may serve an immunoprotective role in multi-organ transplantation.

View details for DOI 10.1016/j.jtcvs.2024.08.031

View details for PubMedID 39187122

Abstract

Ex-vivo normothermic perfusion of cardiac allografts has expanded the donor pool. Utilizing a beating heart implantation method avoids the second cardioplegic arrest and subsequent ischemia reperfusion injury typically associated with ex-vivo heart perfusion. We sought to describe our institutional experience with beating heart transplantation.This was a single-institution retrospective study of adult patients who underwent heart transplantation utilizing ex-vivo heart perfusion (EVHP) and a beating heart implantation technique between October 2022 and March 2024. Primary outcomes of interest included survival, initiation of mechanical circulatory support, and rejection. A sub-analysis of our institutional series of non-beating DCD heart transplantation was also performed.Twenty-four patients underwent isolated heart transplantation with the use of ex-vivo heart perfusion and beating heart implantation between October 2022 and March 2024; 21 (87.5%) received hearts from DCD donors, and 3 (12.5%) patients received hearts from DBD donors. Median follow-up was 192 days (interquartile range of 124-253.5 days), and 23 out of 24 patients (95.8%) were alive at last follow up. No patients required initiation of mechanical circulatory support. The majority of patients had pathological grade 0 rejection at the time of biopsy (n=16, 66.7%), and the median cell-free DNA percent was 0.04% (interquartile range 0.04-0.09). The rate of mechanical circulatory support initiation in the 22-patient non-beating DCD heart transplant cohort was significantly higher at 36.4% (p<0.005).A beating heart implantation technique can be used on DCD and DBD hearts on EVHP and is associated with excellent survival and low levels of rejection.

View details for DOI 10.1016/j.jtcvs.2024.07.058

View details for PubMedID 39111693

Abstract

Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure.Heart sections measuring 250-µm-thick were obtained from mice after pulmonary artery banding (PAB) or debanding PAB surgery and properties of the RV microvascular network were assessed using 3D imaging and quantification. Human heart tissues harvested at the time of transplantation from pulmonary arterial hypertension cases were compared with tissues from control cases with normal RV function.Longitudinal 3D assessment of PAB mouse hearts uncovered complex microvascular remodeling characterized by tortuous, shorter, thicker, highly branched vessels, and overall preserved microvascular density. This remodeling process was reversible in debanding PAB mice in which the RV function recovers over time. The remodeled microvasculature tightly wrapped around the hypertrophied cardiomyocytes to maintain a stable contact surface to cardiomyocytes as an adaptation to RV pressure overload, even in end-stage RV failure. However, microvasculature-cardiomyocyte contact was impaired in areas with interstitial fibrosis where cardiomyocytes displayed signs of hypoxia. Similar to PAB animals, microvascular density in the RV was preserved in patients with end-stage pulmonary arterial hypertension, and microvascular architectural changes appeared to vary by etiology, with patients with pulmonary veno-occlusive disease displaying a lack of microvascular complexity with uniformly short segments.3D deep tissue imaging of the failing RV in PAB mice, pulmonary hypertension rats, and patients with pulmonary arterial hypertension reveals complex microvascular changes to preserve the microvascular density and maintain a stable microvascular-cardiomyocyte contact. Our studies provide a novel framework to understand microvascular adaptation in the pressure-overloaded RV that focuses on cell-cell interaction and goes beyond the concept of capillary rarefaction.

View details for DOI 10.1161/CIRCRESAHA.123.323546

View details for PubMedID 38770652

View details for DOI 10.1016/j.athoracsur.2024.03.038

View details for PubMedID 38621652

Abstract

To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO).Prospective single-center cohort study.University-affiliated tertiary care academic medical center.Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001).Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications.

View details for DOI 10.1053/j.jvca.2024.04.006

View details for PubMedID 38960805

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