Does lung procurement and exposure to Perfadex impact heart transplantation outcomes.

INTRODUCTION: Some studies have shown increased incidence of Primary Graft Dysfunction (PGD) after heart and lung procurement for heart transplant recipients. There have been limited investigations of the impact of lung procurement on heart procurement and the potential effects of the exposure to the type of lung preservation solution, the volume of the lung preservation solution and adequacy of decompression of the heart during heart and lung procurement and the impact on heart transplant outcomes. METHODS: Adult heart transplant recipients in the UNOS database recorded from January 1, 2000 to June 30, 2022 formed the study cohort. Any heart that was procured with a lung team that utilized Perfadex preservation solution (XVIVO, Gothenburg, Sweden) was classified as exposed to Perfadex and otherwise classified as not exposed to Perfadex. Lung procurements performed with a preservation solution other than Perfadex or unknown were excluded (n = 2486). Simple comparisons were made with t-tests or chi-squared tests. Logistic regression models were used to predict 30 day and 1 year survival. Accelerated failure time models were employed to analyze time to death and time to rejection. RESULTS: The cohort consisted of 34 192 heart transplants, of which 21 928 donors were not exposed to Perfadex (64.1%). There were statistically, but not clinically, significant differences in donor characteristics for these groups including in donor age (33.34 ± 11.01 not exposed vs. 30.70 ± 10.69 exposed; p < .001), diabetic donor (4% not exposed vs. 3% exposed; p = .004), and ischemic time (3.28 ± 1.09 h not exposed vs. 3.24 ± 1.05 h exposed; p = .002). In adjusted models, for all included donors, Perfadex exposure was associated with increased short term mortality, but no long term difference (1 year mortality OR 1.10, p = .014). CONCLUSION: Perfadex exposure was associated with increased short-term mortality for heart transplant recipients. Mechanistic investigation is warranted.

Veno-venous ECLS rescue for a heart transplant recipient with COVID-19, a case report.

The potential for increased rates of morbidity of SARS-CoV-2 within immunocompromised populations has been of concern since the pandemic's onset. Transplant providers and patients can face particularly challenging situations, in the current settings as data continues to emerge for the prevention and treatment of the immunocompromised subpopulation. This case report details a patient 9-months post orthotopic heart transplant that developed SARS-CoV-2 infection despite two prior doses of the Pfizer-BioNtech COVID-19 vaccine, and had successful rescue from refractory hypoxemia with veno-venous extracorporeal membrane oxygenation (VV ECLS).

Does donor treatment with inotropes and/or vasopressors impact post-transplant outcomes?

PURPOSE: The purpose was to evaluate the effects of the most commonly used cardiac donor inotropes/vasopressors on subsequent post-heart transplant survival. METHODS: Adult heart transplant recipients from January 2000 to June 2022 were identified in the United Network for Organ Sharing (UNOS) database. Exclusion criteria included: multiorgan transplants, donor age < 15, and recipient age < 18. Donors receiving vasoactive medications at the time of procurement were compared to donors not receiving these medications. Those on vasoactive medications were stratified by medication: phenylephrine, dopamine, dobutamine, norepinephrine and epinephrine, the combination of these agents, and the concomitant administration of vasopressin with any single agent alone or in combination. The primary area of interest was short-and-long-term survival. Survival at 30 days, 1 year, and long-term (Median = 13.6 years) was compared using logistic and Cox models to quantify survival endpoints. RESULTS: A total of 45,198 donors met inclusion criteria and had data on the use of vasoactive agents available. Mean donor age was 32.3 years with 71% male. Vasoactive medications and potential combinations included phenylephrine in 8156 donors (18.0%), dopamine in 9550 (21.1%), dobutamine in 718 (1.6%), epinephrine in 332 (.73%), and norepinephrine in 4854 (10.7%). A total of 25,856 donors (57.2%) were receiving vasopressin at the time of procurement. There was no impact of donor inotropes on 30-day survival. Donors receiving one inotrope and no vasopressin were associated with increased 1 year mortality (OR 1.14; p = .021), as were donors receiving 2+ inotropes and no vasopressin (OR 1.26; p = .006). For individual agents, 1 year mortality was increased for dopamine (OR 1.11; p = .042) and epinephrine (OR 1.59; p = .004). CONCLUSIONS: There is no difference in heart transplant recipient survival at 30 days when the donor is receiving inotropes without vasopressin at the time of procurement. Inotropic support without vasopressin is associated with greater 1 year mortality. The impact of donor inotropic support on long term heart transplant survival, and the interaction with vasopressin warrants further study.

Positive donor blood cultures are not associated with worse heart transplant survival.

BACKGROUND: Recent evidence has demonstrated that transplantation of hearts with blood culture positive donors (BCPDs) to pediatric recipients is safe and effective. Few studies have analyzed the effect of BCPD on adult heart transplant recipients. METHODS: The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from September, 1987 to March, 2021. Exclusion criteria included pediatric donors/recipients, donor ejection fraction <10% or >85%, inactive listed recipients, donors missing blood cultures, and recipients missing follow-up time. Outcomes were compared with fully adjusted logistic models. To account for discrepancies in BCPD and non-BCPD covariates, an inverse proportionally weighted model with regression adjustment (IPWRA) was used. RESULTS: A total of 60 592 donors were non-BCPD, while 4009 were BCPD. 7% of hearts not transplanted were BCPD, while 6% of hearts transplanted were BCPD (p = .001). These rates have been nearly constant since 2005. There were no differences in short term survival between the two groups in the adjusted or IPWRA models (p = .103 and .277, respectively). Additionally, the BCPD group had longer ischemic time (3.24 vs. 3.06 h, p < .001), older donor age (32.73 vs. 31.65 years, p < .001), and older recipient age (52.76 vs. 52.09 years, p = .001). The IPWRA revealed an average additional 3.4 years of overall survival and 2.25 years of graft function for BCPD versus non-BCPD recipients, although these results failed to reach statistical significance (p = .387 and .527, respectively). CONCLUSIONS: Given the need for more donor hearts, donors with positive blood cultures should be considered. Great care in evaluating such patients is advised to eliminate donors with untreated infections, while carefully selected donors can be considered and used.

Do outcomes for heart transplantation differ based on donor and recipient race?

PURPOSE: There are limited data examining the impact of both donor and recipient race on outcomes following orthotopic heart transplant (OHT). The purpose of this study was to evaluate the relationship between donor and recipient race and OHT outcomes. METHODS: The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from January 2000 to March 2018 for donor hearts. A comparison was conducted based on donor and recipient race (White, Black, Hispanic, Other/Unknown). Races for which there were limited numbers were excluded from the analysis (Asian, n = 1292; American Indian, n = 132; Pacific Islander, n = 132, Multiple ethnicities, n = 225). The primary endpoint was survival at 30 days, 1 year survival, and post-transplant rejection. Logistic and Cox models were used to quantify survival endpoints. RESULTS: A total of 41 841 OHT were included. Of the recipients, 29 894 (71%) were White, 8475 (20%) were Black, and 3472 (8%) were Hispanic. Of the donors 27 783 (66%) were White, 6277 (15%) were Black, 6576 (16%) were Hispanic, and 1205 (3%) were Unknown/Other race. In a comparison of recipient demographics, White recipients were older (54.09 ± 12.21 years) compared to Black (49.44 ± 12.83 years) and Hispanic (49.97 ± 13.27 years) recipients. All other differences between groups were not clinically significant. Black recipients were more likely to receive a heart with an "urgent" status (probability .80) compared to White (.73) and Hispanic (.75) recipients (p < .001). Hispanic recipients were more likely to receive a transplant when listed as "non-urgent" (Probability .47) compared to White (.37) and Black (.30) recipients (p < .001). In terms of outcomes, compared to White recipients, Hispanic patients experienced a decreased 30-day survival (OR 1.27; p = .011) and 1-year survival (OR 1.17; p = .016). In comparing Donor/Recipient combinations compared to a White Donor/White Recipient combination, overall survival was decreased in White donor/African American recipient (HR 1.36; p < .001), African American donor/African American recipient (HR 1.41; p < .001) and Hispanic donor/African American recipient (HR 1.30; p < .001) combinations (Table 1). CONCLUSIONS: African American and Hispanic recipients have decreased survival compared to White recipients after heart transplant. The African American donor does not decrease survival. Racial differences still exist in donor and recipient characteristics and recipient outcomes after OHT. Increasing the donor pool for all races and ethnicities would potentially benefit all recipients. Continued study is warranted in order to minimize these differences among recipients and identify factors that could be contributing to decreased survival, in order to optimize outcomes for African American and Hispanic recipients post-transplant and eliminate disparities.

Do vasoactive medications impact donor hearts clinical outcomes in pediatric heart transplantation?

OBJECTIVES: There is limited data examining donor vasopressor and/or inotrope medications (vasoactives) on pediatric orthotopic heart transplant (OHT) outcomes. We aim to evaluate the effects of vasoactives on pediatric OHT outcomes. METHODS: The United Network for Organ Sharing database was retrospectively reviewed from January 2000 to March 2018 for donor hearts. Exclusion criteria included multiorgan transplants and recipient age >18. Donors receiving vasoactives at the time of procurement were compared to donors not on vasoactives, including the number of vasoactives and the type. End-points of interest were survival at 30 days and 1 year as well as post-transplant rejection at 1 year. Logistic and Cox models were used to quantify survival end-points. RESULTS: Of 6462 donors, 3187 (49.3%) were receiving at least one vasoactive. Comparing any vasoactive medication versus none, there was no difference in 30-day survival (p = .27), 1 year survival (p = .89), overall survival (p = .68), or post-transplant rejection (p = .98). There was no difference in 30-day survival for donors receiving 2 or more vasoactive infusions (p = .89), 1 year survival (p = .53), overall survival (p = .75), or post-transplant rejection at 1 year (p = .87). Vasopressin was associated with decreased 30-day mortality (OR = 0.22; p = .028), dobutamine with decreased 1-year mortality (OR = 0.37; p = .036), overall survival (HR = 0.51; p = .003), and decreased post-transplant rejection (HR = 0.63; p = .012). CONCLUSIONS: There is no difference in pediatric OHT outcomes when the cardiac donor is treated with vasoactive infusions at procurement. Vasopressin and dobutamine were associated with improved outcomes. This information can be used to guide medical management and donor selection.

Acute complication posttransplant: primary allograft dysfunction.

PURPOSE OF REVIEW: Heart transplant is the gold standard treatment for patients with end-stage heart failure, improving both quality of life and survival. Despite advances in donor and recipient management, primary graft dysfunction (PGD) remains the most common cause of morbidity and mortality in the early posttransplant period. This review summarizes recent discoveries in the underlying pathophysiology, risk prediction and management of PGD. RECENT FINDINGS: The incidence of PGD appears to be rising and it is not clear whether this is due to better recognition or secular changes in transplant practice. The utilization of donation after circulatory death organs for transplant is a further consideration for the development of PGD. Organ transport systems and preservation techniques may help to prevent PGD. As some of the risk factors for developing PGD remain modifiable, we summarize the current evidence for prevention and management of PGD. SUMMARY: A better understanding will allow us to appropriately manage donors and recipients to reduce the complex interactions that lead to PGD. The development of an international consortium provides the opportunity for deep phenotyping and development of contemporary risk prediction models for PGD, which may reduce the incidence and consequent early mortality associated with heart transplantation.

Proceedings from the metrics forum in heart transplantation for performance monitoring.

Regulatory oversight for heart transplant programs is currently under review by the United Network for Organ Sharing (UNOS). There is concern whether 1-year patient and graft survival truly represent heart transplant center performance. Thus, a forum was organized by the Thoracic and Critical Care Community of Practice (TCC COP) of the American Society of Transplantation (AST) for the heart transplant community to voice their opinions on matters involving program performance monitoring by UNOS. A TCC COP work group was formed to review outcome metrics for adult heart transplantation and culminated in a virtual community forum (72 participants representing 61 heart transplant programs) on November 12-13, 2020. One-year posttransplant survival is still considered an appropriate and important measure to assess program performance. Waitlist mortality and offer acceptance rate as pretransplant metrics could also be useful measures of program performance, recognizing that outside factors may influence these metrics. In depth discussion of these metrics and other issues including auditing thresholds, innovations to reduce risk-averse behavior and personally designed program scorecards are included in this meeting proceedings.

Functional status of heart transplant recipients predicts survival.

INTRODUCTION: Recipient functional status prior to transplantation can significantly impact post-transplant survival. METHODS: The United Network for Organ Sharing database was queried for adult heart transplants including data on functional capacity and from February 1, 2005 to March 1, 2021; there were 32 875 cases included. The four functional categories studied were based on adult daily activities of living and were separated into total assistance required, some assistance required, no assistance required, and near death. Survival outcomes were compared for recipient's pretransplant level of functional status versus those with near death status. These were compared using adjusted logistic regression (odds of death at 30 days and 1 year) and conditional Cox models (overall survival and time until post-transplant rejection). All models were adjusted for donor age, sex, ethnicity, ischemic time, as well as recipient age, sex, ethnicity, length of stay, UNOS region, ventricular assist device, creatinine, days on the waiting list, and status at transplant. RESULTS: There were 12 953 recipients classified as "near death" or "severely disabled"; 7711 "required total assistance in daily living", 7,328 "needed some", and 4883 "needed none". In adjusted models, the probabilities of death for the lowest functioning groups within 30 days and 1 year were 5% and 10%, respectively. Those "requiring total assistance" had analogous probabilities of 3% (OR = 0.58; p < 0.001) and 9% (OR = 0.81; p < 0.001). Those "requiring some assistance" had probabilities of 3% (OR = 0.56; p < 0.001) and 9% (OR = 0.74; p < 0.001). Lastly, those "requiring no assistance" had probabilities of death of 2% (OR = 0.35; p < 0.001) and 7% (OR = 0.63; p < 0.001). CONCLUSION: Recipient functional status assessed pre-transplant and recorded in the UNOS database is a strong predictor of post-transplant survival.

Commentary: The value of nonrandom and uncontrolled.

BACKGROUND: The HeartMate 3 (HM3) (Abbott Laboratories, Illinois) was approved by the FDA in 2018. AIMS: In this issue of the Journal, Bansal et al perform a single center review of their experience with implantation of the HeartMate 3 before and after FDA approval. MATERIALS AND METHODS: The analysis by Bansal et al included 82 patients who were part of the RCT pre-approval group and 92 patients who underwent HM3 implantation after FDA approval. RESULTS: The authors found that the post-approval group was younger, had a higher preoperative INR, was more likely to be undergoing HM3 implantation as part of a bridge to transplant strategy, more likely to have other mechanical support pre-operatively, and included more patients with an INTERMACS profile. CONCLUSION: This study demonstrates the weakness of randomized controlled trials in that they do not reflect the reality of clinical practice which underscores the need for studies such as this one for a complete understanding of any medical intervention or technology.

Next steps in heart transplantation: Diagnosing and treating PGD, where are we?

In this issue of the Journal of Cardiac Surgery, Settepani et al. perform a single center analysis of clinical outcomes for primary graft dysfunction (PGD) in patients undergoing orthotopic heart transplantation. The results of this study underscore the necessity to be proactive in the attempt to prevent PGD to give transplant recipients the best chance at a positive outcome. Further study of PGD should be directed to better understand the underlying pathophysiology and potentially lead to such targeted therapeutic management.

Exploring the ripples of the 2018 organ allocation policy change.

In this issue of the Journal, Patel et al. analyzed the United Network of Organ Sharing database for the impact of the 2018 organ allocation policy changes on outcomes for patients based on BMI. Their work is important for highlighting a population at risk of bias and emphasizes the need for continued study of the ripple effect of the allocation policy changes.

"It Works." Every heart transplant program should have one.

The total artificial heart (TAH) provides full biventricular cardiac replacement, pulsatile perfusion at flows of 7-9 L/min at low filling pressures. This allows organs that are failing to recover and for the potential cardiac recipient to become a better transplant candidate. Postimplant patients are mobile and able to go through physical rehabilitation in a hospital or at home. The risks are acceptable as shown by the authors. TAH use in more transplant centers could save lives in many transplant candidates.

Successful recovery with venovenous ECMO for ARDS after LVAD HeartMate 3 implantation: A case report.

Acute respiratory distress syndrome (ARDS) following left ventricular assist device (LVAD) implantation is a rare complication. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is used as a treatment for severe ARDS and pneumonia. We report the successful use of VV ECMO for ARDS Klebsiella pneumonia following urgent LVAD HeartMate 3 implantation.

Impella 5.0: An intermediate strategy for bridging a patient from infected durable LVAD to cardiac transplant.

Cardiac transplant remains the gold-standard treatment for end-stage heart failure more than 50 years after the procedure was first pioneered. The number of transplant operations performed annually has been limited by the global imbalance of donor organs to recipients. This imbalance helped fuel the development of left ventricular assist devices (LVADs) first as a bridge to cardiac transplant and subsequently as destination therapy. Driveline infection is one of several problems that continue to plague LVADs through several generations of improvement. We present a patient with an infected LVAD driveline exit site that progressed to mediastinitis, pericardial and pump infection. The device was explanted, and the patient supported with an axillary Impella 5.0 as a bridge until the time of transplant. An Impella 5.0 (or 5.5) can be used as an intermediate tool to be able to explant an infected LVAD, with mediastinitis, allowing the patient to clear the infection, and prepare the patient for transplant free of infection. METHODS: The patient consented to the study and case report. The patient signed an informed consent and permission for publication.

Ischemic time and patient outcomes after the 2018 UNOS donor heart allocation system change.

BACKGROUND: The allocation system for heart donors in the United States changed on October 18, 2018. The typical distance from donor hospitals to recipient hospitals has increased as has the ischemic time. We investigated patient outcomes with the new allocation system and the differential effects of ischemic time under both the old and new allocation schemas. METHODS: The United Network for Organ Sharing Registry (UNOS) was queried for data regarding heart transplants occurring from October 1, 1987 to March 1, 2021. In total, 62,301 adult heart transplants were examined. Survival outcomes at 30 days and 1 year and ischemic times were compared via adjusted logistic and Cox models (overall survival and time until post-transplant rejection). RESULTS: Mean ischemic time was slightly increased in the new system (3.43 h vs. 3.03 h, p < .001). Survival differences between old versus new systems were not observed in adjusted models (p = .818). However, there was evidence to suggest longer ischemic times are more detrimental to long-term survival under the new system (hazard ratio [HR] = 1.15 per hour increase; p = .001) versus the old system (HR = 1.08 per hour increase; p < .001), although this relationship did not reach statistical significance (p = .150). CONCLUSIONS: Although travel distances have significantly increased under the new allocation system, survival outcomes remain largely unchanged. Ischemic time is an influential factor in recipient survival that should be limited during organ transport. Further studies on the impact of travel distances and ischemic time under the new allocation system are needed.

Enhanced recovery after surgery multimodality pain regimen performs similar to PRN narcotics on outcomes and pain control after cardiac surgery: A quality improvement project.

BACKGROUND: While enhanced recovery after surgery (ERAS) pathways have been successfully applied for cardiac surgery, there has been limited research directly comparing ERAS protocols to ad hoc narcotic use after surgery. We hypothesized that a standardized ERAS protocol would provide similar pain management and psychoemotional outcomes while decreasing the use of opioids in the hospital and after discharge. METHODS: As part of a 7-month quality improvement project, cardiac surgery patients on a fast-tracked to extubate pathway were assigned pro re nata (PRN) narcotic pain management for 3 months (n = 49). After a 1-month ERAS protocol optimization period, a separate group of patients were given the ERAS protocol (n = 34). Clinical outcomes were gathered, and participants completed a quality of recovery survey that allowed for the assessment of pain and symptom control at four-time points after surgery. RESULTS: Among 83 participants, 66% were male and the mean age was 53 years. There were no differences in patient characteristics between PRN and ERAS groups (all p > .244). There were no differences between ERAS and PRN groups for surgery characteristics (all p > .060), inpatient outcomes (all p > .658), or after-discharge outcomes (all p > .397). Furthermore, across all time-point comparisons, there were no supported differences in patient-reported outcome and pain control between the ERAS and PRN narcotic groups (all p > .075). CONCLUSIONS: An ERAS protocol demonstrated similar patient outcomes and pain control to traditional opioid use for postoperative cardiac surgery patients. Further research is recommended to further confirm the results of this study.

Pre-emptive intraoperative administration of PCC4 in cardiac surgery patients at high risk of bleeding: A pilot study.

BACKGROUND: Four-factor prothrombin complex (PCC4), a concentrate of factors II, VII, IX, and X and proteins C and S, has been used selectively for reversal of oral anticoagulation before surgery. There is data to support PCC4 as opposed to supplemental fresh frozen plasma (FFP) to manage postoperative bleeding following cardiac surgery. The preemptive, intraoperative use of PCC4 in cardiothoracic surgery has not been studied though it may prevent postoperative bleeding, the need for blood transfusion and the risk of transfusion-related acute lung injury, volume overload, and right ventricular (RV) heart failure. The purpose of this study is to evaluate the intraoperative administration of PCC4 to decrease bleeding and lower the rate of blood transfusion. METHODS: A single institution retrospective chart review was conducted from May 2020 to November 2021 of patients who received PCC4 intraoperatively during cardiothoracic surgery of high-risk variety. Patients were evaluated for the type of surgery, demographics, baseline anticoagulation, PCC4 dose, type and quantity of blood transfusion within 72 hours (h) postoperatively, chest tube output, the incidence of RV failure, hypersensitivity reactions, acute kidney injury (AKI), thrombosis, acute lung injury, and mortality within 45 days of the operative dose of PCC4. RESULTS: Thirty-five patients received PCC4 at a mean dose of 2920 units (U). Sixty-five percent of cases were left ventricular assist devices (LVADs) or heart transplants. The protocol is to use PCC4 30 units (U)/kg immediately after the completion of protamine administration. Inclusion criteria are cardiothoracic surgery with increased risk of postoperative right heart failure commonly secondary to blood product transfusion, or cardiothoracic surgery associated with increased risk of bleeding, including heart transplant, LVAD implant, aortic dissection, and redo sternotomy (e.g., coronary artery bypass). Total chest tube output was recorded as a mean of 757 ml for 24 h after surgery (32 ml/h). Overall median event rates of FFP and red blood cell (RBC) transfusions were 0 (interquartile range [IQR]: 0-3 U) and 4 (IQR: 2-5 U). Overall, 43% and 89% of cases received FFP and RBC, respectively. There was one occurrence of RV failure, one occurrence of AKI requiring renal replacement therapy, one occurrence of venoarterial extracorporeal membrane oxygenation, one occurrence of venous thromboembolism related to a central venous access line, and one death unrelated to surgery or PCC4 that was attributed to advanced heart failure not amenable to advanced therapies. CONCLUSION: Overall patients received a low rate of blood transfusion, had minimal chest tube output, and there was a small incidence of right heart failure. Patients did not have an increased risk of adverse effects such as AKI or venous thromboembolism. A randomized controlled clinical trial comparing the observed dose and timing of PCC4 versus routine postoperative bleeding management with blood product transfusion is recommended.

Better together: a reappraisal of heterotopic heart transplantation.

Heterotopic heart transplantation (HHT) is rare in the modern era. When used as a biologic left ventricular assist, HHT provides pulsatile flow, supports the left ventricle with a physiologic cardiac output, responds to humoral stimuli, and with modern immunosuppression may offer long-term untethered survival. This study was undertaken to compare survival of HHT with orthotopic heart transplantation (OHT) to assess its viability in the modern era. In the United Network for Organ Sharing database, from January 1999 to December 2020, there were 27691 bicaval OHT, 13836 biatrial OHT, 1271 total OHT, and 51 HHT with sufficient follow-up. Survival was analyzed using restricted mean survival time (RMST) through 4 years as the outcome. In the first 4 years after transplant, compared with HHT, differences in RMST were 0.1 years (99% CI: -0.4 to 0.5 years) for bicaval OHT, 0.0 years (99% CI: -0.4 to 0.5 years) for biatrial OHT, and 0.0 years (99% CI: -0.5 to 0.4 years) for total OHT. In this cohort, survival was indistinguishable between HHT and OHT recipients in the first four years. Thus, HHT might be a viable alternative to durable mechanical circulatory assist particularly with size mismatched grafts or for patients with refractory pulmonary hypertension.

Looking at cardiac transplantation through a 20-year retrospective study-invited commentary.

The authors present an excellent large cohort review and complete analysis of long-term heart transplant survival including multiple institutions. Most studies on long-term heart transplant survival have single-center institutional experience. The authors present a comprehensive national review of the United Network for Organ Sharing Database (UNOS). The paper reflects the early transplant era through 1998 and demonstrates the long-term survival of this time.