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.

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.

"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.

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.

The effects of increased donor support time from organ donation referral to donor procurement on heart transplant recipient survival.

INTRODUCTION: Given the known deleterious cardiac effects of brain death (BD) physiology, we hypothesized that time from cardiac donation referral to procurement (donor support time [DST]), would negatively impact cardiac transplant recipient survival. METHODS: The United Network for Organ Sharing database was queried from 2007 to 2018, identifying 22,593 donor hearts for analysis. Multivariate logistic models for 30-day and 1-year survival, as well as Cox models for overall survival and posttransplant rejection, were used to assess adjusted outcomes. RESULTS: median DST was 3 days (interquartile range: 2-5 days). Ischemic time; distance between donor and recipient hospitals; and recipient age, creatinine, waitlist time, and length of stay were adjusted predictors of survival and rejection. DST was not associated with either outcome in aggregate; however, differential association by donor race was identified, with DST in any race recipient associated with 4% higher odds of 1-year mortality (p = .001; p value for interaction .005) but only a trend towards worse overall mortality (p = .064; p value for interaction .046). CONCLUSION: Thus, duration of exposure to BD physiology may have a differential impact on recipient outcomes based on donor race, suggesting that additional research is needed on donor immunologic, socioeconomic, and healthcare access factors that may impact cardiac transplant recipient outcomes.

Does pediatric heart transplant survival differ with various cardiac preservation solutions?

BACKGROUND: Few studies directly compare outcomes between the most commonly used preservation solutions in pediatric heart transplantation in a large cohort of recipients. The purpose of this study is to investigate the effect of cardiac preservation solution on survival in pediatric heart transplant recipients. METHODS: The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from 01/2004-03/2018 for pediatric donor hearts. Saline, University of Wisconsin (UW), "cardioplegia," Celsior, and Custodiol preservation solutions were evaluated. The primary endpoints were recipient survival at 30 days, 1 year, and long term. RESULTS: After exclusion criteria, 3012 recipients had preservation solution data available. The most common preservation solution used was UW in 1203 patients (40%), followed by Celsior in 542 (18%), cardioplegia in 461 (15%), saline in 408 (14%), and Custodiol in 398 (13%). Survival of recipients whose donor hearts were procured with UW was as follows: 97%-30 day, 92%-1 year; Celsior: 97%-30 day, 92%-1 year; cardioplegia: 97%-30 day, 91%-1 year; saline: 97%-30 day, 91%-1 year; and Custodiol: 96%-30 day and 92%-1 year. Analysis of Cox models for 30-day and long-term survival revealed no statistical differences when comparing UW to Celsior (p = .333), cardioplegia (p = .914), saline (p = .980), or Custodiol (p = .642) in adjusted models. CONCLUSIONS: There were no significant differences in 30-day or 1-year survival detected between commonly used preservation solutions in the pediatric heart transplant population.

The Effect of Cardiac Preservation Solutions on Heart Transplant Survival.

BACKGROUND: Limited data exist that compare the predominant cardiac preservation solutions (CPSs). MATERIALS AND METHODS: The United Network for Organ Sharing database was retrospectively reviewed from January 1, 2004 to March 31, 2018, for donor hearts. Of 34,614 potential donors, 21,908 remained after applying the exclusion criteria. The CPS analyzed included saline, the University of Wisconsin (UW), cardioplegia, Celsior, and Custodiol. The primary endpoints were recipient survival and posttransplant rejection. Logistic and Cox models were used to quantify survival endpoints. RESULTS: Saline was used as the CPS in 2549 patients (12%), UW in 10,549 (48%), cardioplegia in 1307 (6%), Celsior in 5081 (23%), and Custodiol in 2422 (11%). Donor age ranged from 15 to 68 y (mean = 32.0 y, median = 30.0 y), and 71% were male. Adjusted survival probabilities of recipients whose donor hearts were procured with saline was 96% 30 d, 90% 1 y, UW: 97% 30 d, 92% 1 y, cardioplegia: 95% 30 d, 87% 1 y, Celsior: 96% 30 d, 90% 1 y, and Custodiol: 97% 30 d, 92% 1 y. When these comparisons were adjusted for donor age, sex, ethnicity, ischemic time, recipient age, sex, ethnicity, creatinine, ventricular assist device (VAD), length of stay, region and days on waiting list, cardioplegia solution was demonstrated to have a higher risk of death (30 d, 1 y, overall) and posttransplant rejection versus UW (odds ratio 1.70, P = 0.001; odds ratio 1.63, P < 0.001; hazard ratio 1.22, P < 0.001; hazard ratio 1.21, P < 0.001, respectively). CONCLUSIONS: Cardioplegia solutions for cardiac preservation are associated with a higher mortality in heart transplant recipients.

Donor Utilization in the Recent Era: Effect of Sex, Drugs, and Increased Risk.

BACKGROUND: Heart transplantation volumes have increased in recent years, yet less than a third of donors are typically accepted for transplantation. Whether donor sex, donor drug use, or perception of increased risk affects utilization for transplantation is unclear. METHODS: The United Network for Organ Sharing database was queried for donors from January 1, 2007, to December 31, 2017. Donor toxicology was collected when available. Multivariate analysis was conducted to examine correlations with donor utilization. RESULTS: Between January 1, 2007, and December 31, 2017, there were 87 816 heart donors aged ≥15 years. The mean age was 42.7±15.8 years, and 24 831 donors (28.3%) were utilized for heart transplantation. Subsequent analyses focused on donors between 15 and 39 years old. The strongest associations with donor acceptance were for male donor sex, blood type, hepatitis C antibody, donor age, left ventricular hypertrophy, and history of donor drug use. After removing hepatitis C, Public Health Service Increased Risk was identified as a strong negative predictor. Most positive drug toxicology results were associated with donor nonuse except for donors between 15 and 19 years of age. Exceptions included alcohol, marijuana, and cocaine. Opiates were associated with less utilization at all donor ages. The Public Health Service Increased Risk status was associated with significantly less utilization in all age groups except 15- to 19-year-old donors. CONCLUSIONS: While male donors were preferentially utilized, donors with drug use or those deemed Public Health Service Increased Risk were significantly less utilized for heart transplantation. Further consideration of such donors would be appropriate particularly as the demand for transplantation continues to increase.

Venoarterial extracorporeal membrane oxygenation is a viable option as a bridge to heart transplant.

OBJECTIVE: Venoarterial extracorporeal membrane oxygenation is a rescue therapy for patients in cardiogenic shock. We hypothesize that patients bridged to heart transplant with extracorporeal membrane oxygenation have decreased survival. METHODS: The United Network of Organ Sharing database was retrospectively reviewed from January 1, 1999, to March 31, 2018, for heart transplant recipients. Recipients bridged with any form of mechanical support and those without support were compared with recipients bridged with extracorporeal membrane oxygenation. The primary end point was restricted mean survival time through 16.7 years. RESULTS: Of 26,918 recipients, 15,076 required no pretransplant mechanical support (56.0%). Support patients included 9321 with left ventricular assist devices (34.6%), 53 with right ventricular assist devices (0.2%), 258 with total artificial hearts (1.0%), 686 with biventricular assist devices (2.6%), 1378 with intra-aortic balloon pumps (5.1%), and 146 who required extracorporeal membrane oxygenation (0.5%). In the first 16.7 years post-transplant, compared with recipients bridged with extracorporeal membrane oxygenation, estimated adjusted restricted mean survival time was higher in patients who required no mechanical support (16.6 months [14.0-19.4]) and patients with a left ventricular assist device (16.5 months [99% confidence interval, 13.9-19.2]), an intra-aortic balloon pump (11.2 months [8.3-14.7]), or a biventricular assist device (6.6 months [3.6-10.3]). Restricted mean survival time in patients with a right ventricular assist device or a total artificial heart was similar to patients with extracorporeal membrane oxygenation. CONCLUSIONS: Recipients bridged with extracorporeal membrane oxygenation were estimated to survive 16.6 months less than nonmechanical circulatory support recipients. Bridge to heart transplant with extracorporeal membrane oxygenation is a viable option, and these patients should be considered transplant candidates.

A method for anticoagulation of children on mechanical circulatory support.

Anticoagulation of children on mechanical circulatory support presents a challenge. We implanted 28 devices in children and infants using a consistent anticoagulation protocol. We performed a retrospective review of all children implanted in our program with mechanical assist devices since 1997. Heparin, dipyridamole, and aspirin were used for anticoagulation and antiaggregation. Coagulation monitoring included thromboelastography (TEG), platelet aggregration studies, international normalized ratio, partial thromboplastin time, and platelet count. Twenty-eight children, ages 1 month to 16 years (mean 5.3; median 2.4 years), were implanted for 3-107 days (mean 27; median 17). Eighteen received left ventricular assist devices, seven received biventricular assist devices, and three received total artificial hearts. Adverse events during the 720 days of device support included the following: six (21%) reoperations for bleeding; seven strokes (25%): two fatal, two with a mild residual deficit, and three without deficit; and three (11%) visceral emboli: two fatal and one nonfatal. There were eight deaths (29%). Causes of death were embolic (four), graft failure post-transplantation (one), preimplant anoxic brain damage (two), and postexplant heart failure (one). 24/28 (86%) survived to transplantation or weaning from device and 20/28 (71%) were discharged from the hospital, 10 after transplantation and 10 after native heart recovery. All 20 early survivors survived long term. We describe an anticoagulation protocol based upon TEG and platelet aggregation studies and using heparin, aspirin, and dipyridamole. Adequate anticoagulation is more difficult in children. However, 71% of the patients in our study survived long term.

Tricuspid regurgitation after orthotopic heart transplantation.

BACKGROUND: Tricuspid regurgitation (TR) is a relatively common abnormality in normal adults as well as after orthotopic heart transplantation (OHT). A few studies have shown reduction in the incidence of TR after OHT by total bicaval surgical anastomosis technique. Other studies reported no significant difference in the rates of TR between the standard and bicaval techniques. OBJECTIVE: Evaluate and compare the degree of TR after OHT by standard and bicaval anastomosis techniques. METHOD: Echocardiograms from the first 56 consecutive patients that had the total bicaval surgical technique performed were retrospectively reviewed and compared with the last 57 consecutive patients who had the standard biatrial technique performed. Patients with adequate two-dimensional and Doppler echocardiograms were included. RESULTS: No statistical difference was observed for each grade of TR at both early and late time points. No significant difference was observed between the TR velocities of both biatrial and bicaval anastomosis patients at different periods. CONCLUSION: There appears to be no difference between the TR severity and TR velocity at early and late time points regardless of anastomotic technique.

Donor heart and lung procurement: A consensus statement.

Heart and lung procurements are multiphased processes often accompanied by an array of complex logistics. Approaches to donor evaluation and management, organ procurement, and organ preservation vary among individual procurement teams. Because early graft failure remains a major cause of mortality in contemporary thoracic organ transplant recipients, we sought to establish some standardization in the procurement process. This paper, in this vein, represents an international consensus statement on donor heart and lung procurement and is designed to serve as a guide for physicians, surgeons, and other providers who manage donors to best optimize the clinical status for the procurement of both heart and lungs for transplantation. Donation after brain death (DBD) and donation after circulatory determination death (referred to as donation after circulatory death [DCD] for the remainder of the paper) for both heart and lung transplantation will be discussed in this paper. Although the data available on DCD heart donation are limited, information regarding the surgical technique for procurement is included within this consensus statement. Furthermore, this paper will focus on adult DBD and DCD heart and lung procurement. Currently, no certification, which is either recognized and/or endorsed by the transplant community at large, exists for the training of a cardiothoracic procurement surgeon. Nevertheless, establishing a training curriculum and credentialing requirements are beyond the scope of this paper.

Compelling argument for an agitated saline bubble study prior to cardiac transplantation.

Cardiac transplant recipients with patent foramen ovale (PFO) are at risk for right-to-left shunting. Failure to identify this abnormality can have serious posttransplant consequences. In this article, we describe a cardiac transplant recipient with hypoxemia where a PFO was diagnosed postoperatively despite direct surgical investigation at the time of orthotopic heart transplantation (OHT). Transthoracic echocardiography with bubble study is relatively inexpensive, noninvasive, and simple and can be a useful method to identify PFO/atrial septal defect. Thus, authors recommend critically screening both donor and recipient hearts prior to OHT.

Cardiac replacement with a total artificial heart as a bridge to transplantation.

BACKGROUND: The CardioWest Total Artificial Heart orthotopically replaces both native cardiac ventricles and all cardiac valves, thus eliminating problems commonly seen in the bridge to transplantation with left ventricular and biventricular assist devices, such as right heart failure, valvular regurgitation, cardiac arrhythmias, ventricular clots, intraventricular communications, and low blood flows. METHODS: We conducted a nonrandomized, prospective study in five centers with the use of historical controls. The purpose was to assess the safety and efficacy of the CardioWest Total Artificial Heart in transplant-eligible patients at risk for imminent death from irreversible biventricular cardiac failure. The primary end points included the rates of survival to heart transplantation and of survival after transplantation. RESULTS: Eighty-one patients received the artificial-heart device. The rate of survival to transplantation was 79 percent (95 percent confidence interval, 68 to 87 percent). Of the 35 control patients who met the same entry criteria but did not receive the artificial heart, 46 percent survived to transplantation (P<0.001). Overall, the one-year survival rate among the patients who received the artificial heart was 70 percent, as compared with 31 percent among the controls (P<0.001). One-year and five-year survival rates after transplantation among patients who had received a total artificial heart as a bridge to transplantation were 86 and 64 percent. CONCLUSIONS: Implantation of the total artificial heart improved the rate of survival to cardiac transplantation and survival after transplantation. This device prevents death in critically ill patients who have irreversible biventricular failure and are candidates for cardiac transplantation.

Real-time sonography in central venous access for endomyocardial biopsy in cardiac transplantation patients.

BACKGROUND: Endomyocardial biopsy remains the gold standard to assess cardiac rejection in cardiac transplantation patients. The aim of this study is to evaluate the supportive role and benefits of real-time sonography in central venous access for cardiac biopsy. STUDY DESIGN: Between January and September 2006, a retrospective review was carried out for the performance of central venous access using real-time sonography on 74 transplantion patients undergoing 305 cardiac biopsies by a single operator. The study included 56 male and 18 female patients, some of whom had severe dyspnea, obesity, dehydration, peripheral and pulmonary edema. RESULTS: All patients underwent successful central venous access using real-time ultrasonic guidance. With increasing experience as a sonographer, central venous access became less invasive and traumatic and more precise and successful. The supportive role of real-time sonography was associated with less major complications and greater patient comfort, even among conscious patients with severe dyspnea and obesity in non-Trendelenburg position using routine local anesthesia. CONCLUSIONS: Use of real-time sonography during percutaneous sheath insertion of the right internal jugular vein and the right subclavian vein provides an improved means to safe and quick access for cardiac biopsies with high success rates and low complication rates.

Amiodarone prophylaxis for atrial fibrillation after cardiac surgery: meta-analysis of dose response and timing of initiation.

STUDY OBJECTIVE: To investigate a possible dose-response relationship between amiodarone and reduction in incidence of postoperative atrial fibrillation, and to determine whether pre- or postoperative initiation of amiodarone is superior. DESIGN: Meta-analysis of randomized controlled trials. DATA SOURCE: MEDLINE and EMBASE databases and the Cochrane Central Register of Controlled Trials for English-language reports published between 1966 and December 2005. MEASUREMENTS AND MAIN RESULTS: Of 23 identified randomized controlled trials of amiodarone prophylaxis of postoperative atrial fibrillation, 14 were included in the final analysis. These studies enrolled a total of 2864 patients. For each study, the total administered amiodarone dose--categorized as low (< 3000 mg), medium (3000-5000 mg), or high (> 5000 mg)--and preoperative versus postoperative initiation were aggregated by using meta-analytic techniques. The incidence of postoperative atrial fibrillation was significantly reduced by amiodarone compared with placebo (p<0.001). Although the odds of developing atrial fibrillation appeared to be somewhat higher in the low-dose group, no significant differences were noted in the odds ratios (ORs) of developing atrial fibrillation among the low-, medium-, and high-dose groups: OR 0.58, 95% confidence interval (CI) 0.44-0.77; OR 0.45, 95% CI 0.30-0.69; and OR 0.44, 95% CI 0.33-0.58; respectively (p=0.238). In addition, the ORs for atrial fibrillation development associated with preoperative and postoperative initiation of amiodarone were not significantly different (OR 0.50, 95% CI 0.39-0.63; and OR 0.48, 95% CI 0.37-0.63; respectively, p=0.862). CONCLUSION: Total amiodarone doses of 3000 mg or higher may be more effective than lower doses in reducing the rate of postoperative atrial fibrillation after cardiac surgery. Preoperative initiation of amiodarone appears to be unnecessary. These findings require confirmation in prospective, randomized trials.

Total Artificial Heart Implantation after Excision of Right Ventricular Angiosarcoma.

Primary cardiac sarcomas, although rare, are aggressive and lethal, requiring thorough surgical resection and adjuvant chemotherapy for the best possible outcome. We report the case of a 32-year-old woman who underwent total artificial heart implantation for right-sided heart failure caused by right ventricular angiosarcoma. For the first several weeks in intensive care, the patient recovered uneventfully. However, a postoperative liver biopsy indicated hepatocellular injury consistent with preoperative chemotherapy. She developed continuing liver failure, from which she died despite good cardiac function.