Impact of controlled hypothermic preservation on outcomes following heart transplantation.

BACKGROUND: Severe primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant, but the impact of donor organ preservation conditions on severity of PGD and survival has not been well characterized. METHODS: Data from US adult heart-transplant recipients in the Global Utilization and Registry Database for Improved Heart Preservation-Heart Registry (NCT04141605) were analyzed to quantify PGD severity, mortality, and associated risk factors. The independent contributions of organ preservation method (traditional ice storage vs controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression. RESULTS: Among 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% [37/559] vs 10.4% [47/452], p = 0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% [17/281] vs 12.1% [34/281], respectively; p = 0.018). The Kaplan-Meier terminal probability of 1-year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD (p < 0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation. CONCLUSIONS: Severe PGD is the deadliest complication of heart transplantation and is associated with a 7.8-fold increase in probability of 1-year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating post-transplant morbidity.

Outcomes in Heart Transplant Recipients by Bridge to Transplant Strategy When Using the SherpaPak Cardiac Transport System.

The last several years have seen a rise in use of mechanical circulatory support (MCS) to bridge heart transplant recipients. A controlled hypothermic organ preservation system, the SherpaPak Cardiac Transport System (SCTS), was introduced in 2018 and has grown in utilization with reports of improved posttransplant outcomes. The Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN)-Heart registry is an international, multicenter registry assessing outcomes after transplant using the SCTS. This analysis examines outcomes in recipients bridged with various MCS devices in the GUARDIAN-Heart Registry. A total of 422 recipients with donor hearts transported using SCTS were included and identified. Durable ventricular assist devices (VADs) were used exclusively in 179 recipients, temporary VADs or intra-aortic balloon pump (IABP) in 197, and extracorporeal membrane oxygenation (ECMO) in 14 recipients. Average ischemic times were over 3.5 hours in all cohorts. Severe primary graft dysfunction (PGD) posttransplant increased across groups (4.5% VAD, 5.1% temporary support, 21.4% ECMO), whereas intensive care unit (ICU) length of stay (18.2 days) and total hospital stay (39.4 days) was longer in the ECMO cohort than the VAD and IABP groups. A comparison of outcomes of MCS bridging in SCTS versus traditional ice revealed significantly lower rates of both moderate/severe right ventricular (RV) dysfunction and severe PGD in the SCTS cohort; however, upon propensity matching only the reductions in moderate/severe RV dysfunction were statistically significant. Use of SCTS in transplant recipients with various bridging strategies results in excellent outcomes.

Recipient Outcomes With Extended Criteria Donors Using Advanced Heart Preservation: An Analysis of the GUARDIAN-Heart Registry.

BACKGROUND: The prevalence of end-stage heart failure and patients who could benefit from heart transplantation requires an expansion of the donor pool, relying on the transplant community to continually re-evaluate and expand the use of extended criteria donor organs. Introduction of new technologies such as the Paragonix SherpaPak Cardiac Transport System aids in this shift. We seek to analyze the impact of the SherpaPak system on recipient outcomes who receive extended criteria organs in the GUARDIAN-Heart Registry. METHODS: Between October 2015 and December 2022, 1,113 adults from 15 US centers receiving donor hearts utilizing either SherpaPak (n = 560) or conventional ice storage (ice, n = 453) were analyzed from the GUARDIAN-Heart Registry using summary statistics. A previously published set of criteria was used to identify extended criteria donors, which included 193 SherpaPak and 137 ice. RESULTS: There were a few baseline differences among recipients in the 2 cohorts; most notably, IMPACT scores, distance traveled, and total ischemic time were significantly greater in SherpaPak, and significantly more donor hearts in the SherpaPak cohort had >4 hours total ischemia time. Posttransplant mechanical circulatory support utilization (SherpaPak 22.3% vs ice 35.0%, p = 0.012) and new extracorporeal membrane oxygenation/ventricular assist device (SherpaPak 7.8% vs ice 15.3%, p = 0.033) was significantly reduced, and the rate of severe primary graft dysfunction (SherpaPak 6.2% vs ice 13.9%, p = 0.022) was significantly reduced by over 50% in hearts preserved using SherpaPak. One-year survival between cohorts was similar (SherpaPak 92.9% vs ice 89.6%, p = 0.27). CONCLUSIONS: This subgroup analysis demonstrates that SherpaPak can be safely used to utilize extended criteria donors with low severe PGD rates.

The Society of Thoracic Surgeons Intermacs 2023 Annual Report: Focus on Magnetically Levitated Devices.

The 14th Annual Report from The Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) describes outcomes of 27,493 patients with a continuous-flow left ventricular assist device (LVAD) from the past decade (2013-2022). In 2022, 2517 primary LVADs were implanted, of which 2512 (99.8%) were fully magnetically levitated (Mag-Lev) devices. This shift to nearly exclusive use of a Mag-Lev device led us to examine its outcomes compared with contemporary (2018-2022) and historical (2013-2017) non-Mag-Lev cohorts. Patients supported by a Mag-Lev device (n = 10,920) had a higher 1- and 5-year survival of 86% (vs 79% and 81%, P < .0001) and 64% (vs 44% and 44%, P < .0001), respectively, than those receiving non-Mag-Lev devices during the contemporary and historical eras. Over 5 years, freedom from gastrointestinal bleeding (72% vs 60%, P < .0001), stroke (87% vs 67%, P < .0001), and device malfunction/pump thrombus (83% vs 54%, P < .0001), but not device-related infection (61% vs 64%, P = .93), was higher with Mag-Lev devices compared with non-Mag-Lev support during the contemporary era. In this large primacy cohort of real-world patients with advanced heart failure, this report underscores marked improvements in short- and intermediate-term survival and reduction of adverse events with a contemporary Mag-Lev LVAD.

Early elevated donor-derived cell-free DNA levels in heart transplant recipients following precision-controlled cardiac transport system or ice-cooled organ transport.

BACKGROUND: Recent innovations in temperature-controlled cardiac transportation allow for static hypothermic preservation of transplant organs during transportation. We assessed differences in donor-derived cell-free DNA (dd-cfDNA) using the SherpaPak cardiac transport system (SCTS) and traditional ice transportation. METHODS: Single-organ heart transplant recipients between January 2020 and January 2022 were included if they had dd-cfDNA measures ≤6 weeks post-transplant along with the baseline biopsy at 6 weeks as part of the surveillance protocol and no biopsy-confirmed rejection ≤90 days. Elevated dd-cfDNA ≥.20% were compared between groups using logistic regression including a subject effect. RESULTS: Of 65 hearts transplanted, 30 were transported with SCTS and 35 on ice. Recipient characteristics were similar between groups. Donors in the SCTS group were older (34 vs. 40 years, p = .04) with a longer total ischemic time (171 vs. 212 min, p = .002). Recipients in the SCTS group had a greater risk of elevated dd-cfDNA unadjusted and adjusted for donor age, and prolonged ischemic times > 3.5 h (Unadjusted odds ratio: 4.9, 95%-CI: 1.08-22.5, p = .039 and Adjusted odds ratio: 5.5, 95%-CI: 1.03-29.6, p = .046). Primary graft dysfunction rates and 1-year mortality were comparable between groups. CONCLUSION: Elevated dd-cfDNA in patients procured with SCTS may indicate that graft injury was not negated relative to ice transport. However, there were no clinical differences noted in short or long-term outcomes including mortality despite a longer ischemic time in the SCTS group.

A Paradigm Shift in Heart Preservation: Improved Post-transplant Outcomes in Recipients of Donor Hearts Preserved With the SherpaPak System.

Traditional ice storage has been the historic standard for preserving donor's hearts. However, this approach provides variability in cooling, increasing risks of freezing injury. To date, no preservation technology has been reported to improve survival after transplantation. The Paragonix SherpaPak Cardiac Transport System (SCTS) is a controlled hypothermic technology clinically used since 2018. Real-world evidence on clinical benefits of SCTS compared to conventional ice cold storage (ICS) was evaluated. Between October 2015 and January 2022, 569 US adults receiving donor hearts preserved and transported either in SCTS (n = 255) or ICS (n = 314) were analyzed from the Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN-Heart) registry. Propensity matching and a subgroup analysis of >240 minutes ischemic time were performed to evaluate comparative outcomes. Overall, the SCTS cohort had significantly lower rates of severe primary graft dysfunction (PGD) ( p = 0.03). When propensity matched, SCTS had improving 1-year survival ( p = 0.10), significantly lower rates of severe PGD ( p = 0.011), and lower overall post-transplant MCS utilization ( p = 0.098). For patients with ischemic times >4 hours, the SCTS cohort had reduced post-transplant MCS utilization ( p = 0.01), reduced incidence of severe PGD ( p = 0.005), and improved 30-day survival ( p = 0.02). A multivariate analysis of independent risk factors revealed that compared to SCTS, use of ice results in a 3.4-fold greater chance of severe PGD ( p = 0.014). Utilization of SCTS is associated with a trend toward increased post-transplant survival and significantly lower severe PGD and MCS utilization. These findings fundamentally challenge the decades-long status quo of transporting donor hearts using ice.

HeartMate 3 Explantation Using Felt Plug for Ventriculotomy Occlusion.

Left ventricular assist devices (LVAD) can be utilized for heart failure patients as a bridge to transplant, bridge to destination, or bridge to recovery. Given the lack of a universally accepted consensus for assessing myocardial recovery, techniques and strategies in LVAD explantation also vary. In addition, the incidence of LVAD explantation remains relatively low, and surgical techniques of explantation continue to be areas of interest. Our approach using a felt-plug Dacron technique is an effective way to preserve left ventricular geometry and cardiac function.

COMPETENCE Trial: The EVAHEART 2 continuous flow left ventricular assist device.

BACKGROUND: Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices. METHODS: A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio. RESULTS: The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively. CONCLUSIONS: The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3.

Origin of the Right Coronary Artery From the left Sinus of Valsalva in a Donor Heart With Unsuccessful Repair.

Described herein is a 62-year-old man who had orthotopic heart transplantation (OHT) because of severe heart failure secondary to idiopathic dilated cardiomyopathy. Because of continued symptoms of heart failure, a coronary angiogram was performed 3 years after the OHT and it showed anomalous origin of the right coronary artery (RCA) from the left sinus of Valsalva. As a consequence, an operation was performed to transfer the origin of the RCA to the right sinus of Valsalva. Unfortunately, the lumen of the RCA clotted off shortly after the operative procedure. Because of clinical evidence of rejection, the donor heart was replaced 4 years later providing the opportunity to study the previously transferred anomalous RCA.

Acute Dissection of Epicardial Coronary Arteries Shortly Following Full Term Delivery Resulting in Acute Myocardial Infarction and Leading to Orthotopic Heart Transplantation.

Described herein is a 28-year-old woman who developed acute dissection of the left main, left anterior descending, and left circumflex coronary arteries shortly after delivering a full-term normal infant. The consequence was acute myocardial infarction leading to a severely depressed left ventricular ejection fraction (<10%) and resulting in life-saving orthotopic heart transplantation procedure not previously reported in patients with spontaneous isolated coronary dissection.

Cardiac sarcoidosis diagnosed after orthotopic heart transplantation and clinically mimicking arrhythmogenic right ventricular cardiomyopathy.

Described herein is a 71-year-old man who underwent orthotopic heart transplant (OHT) for chronic severe heart failure secondary to cardiac sarcoidosis (CS) devoid of non-caseating granulomas but nevertheless characteristic of CS. Clinically, his heart disease had suggested the presence of arrhythmogenic right ventricular cardiomyopathy.

Venovenous extracorporeal membrane oxygenation for patients with refractory coronavirus disease 2019 (COVID-19): Multicenter experience of referral hospitals in a large health care system.

BACKGROUND: The benefit of extracorporeal membrane oxygenation (ECMO) for patients with severe acute respiratory distress from coronavirus disease 2019 refractory to medical management and lung-protective mechanical ventilation has not been adequately determined. METHODS: We reviewed the clinical course of 37 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection supported by venovenous ECMO at 4 ECMO referral centers within a large health care system. Patient characteristics, progression of hemodynamics and inflammatory markers, and clinical outcomes were evaluated. RESULTS: The patients had median age of 51 years (interquartile range, 40-59), and 73% were male. Peak plateau pressures, vasopressor requirements, and arterial partial pressure of carbon dioxide all improved with ECMO support. In our patient population, 24 of 37 patients (64.8%) survived to decannulation and 21 of 37 patients (56.8%) survived to discharge. Among patients discharged alive from the ECMO facility, 12 patients were discharged to a long-term acute care or rehabilitation facility, 2 were transferred back to the referring hospital for ventilatory weaning, and 7 were discharged directly home. For patients who were successfully decannulated, median length of time on ECMO was 17 days (interquartile range, 10-33.5). CONCLUSIONS: Venovenous ECMO represents a useful therapy for patients with refractory severe acute respiratory distress syndrome from coronavirus disease 2019.

A system-wide extracorporeal membrane oxygenation quality collaborative improves patient outcomes.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) use in adult patient populations has grown rapidly with wide variation in practices and outcomes. We evaluated the impact on patient outcomes, resource use, and costs of an initiative to coordinate and standardize best practices across ECMO programs within a large integrated health care system. METHODS: The ECMO Collaborative Project brought clinicians and service-line leaders from 4 programs within a single health care system together with operational subject matter experts tasked with developing and implementing standardized guidelines, order sets, and an internal database to support an automated quarterly report card. Patient outcomes, resource use, and financial measures were compared for the 16 months before (January 2017 to April 2018; "precollaborative," n = 185) versus the 14 months after (November 2018 to December 2019, "postcollaborative," n = 243) a 6-month implementation and blanking period. Subset analyses were performed for venoarterial ECMO, venovenous ECMO, and extracorporeal cardiopulmonary resuscitation. RESULTS: Survival to discharge/transfer increased significantly (in-hospital mortality hazard ratio, 0.75; 95% confidence interval [95% CI], 0.58-0.99) for the postcollaborative versus the precollaborative period (107/185, 57.8% vs 113/243, 46.5%, P = .03), predominantly due to improvement among patients receiving venoarterial ECMO (hazard ratio, 0.61; 95% CI, 0.41-0.91). The percentage of patients successfully weaned from ECMO increased from 58.9% (109/185) to 70% (170/243), P = .02. Complication rates decreased by 40% (incidence rate ratio, 0.60; 95% CI, 0.49-0.72). No significant changes were observed in ECMO duration, intensive care unit or hospital length of stay, or cost-per-case; payment-per-case and contribution-margin-per-case both decreased significantly. CONCLUSIONS: The ECMO Collaborative Project improved survival to discharge/transfer, weaning rates and complications, without additional costs, through coordination and standardization across ECMO programs within a health care system.

Laparoscopic repair of large diaphragmatic hernia after left ventricular assist device implantation followed by orthotopic heart transplantation.

In patients with advanced heart failure and deteriorating clinical status, a left ventricular assist device (LVAD) can be used as a bridge to transplantation or as an alternative to transplantation. An uncommon complication of orthotopic heart transplant or LVADs is diaphragmatic hernia during implantation or explantation of the device. We describe a patient with a diaphragmatic hernia with incarcerated colon and small bowel treated previously with a HeartMate 3 LVAD and subsequent transplantation. This case highlights the need to consider the diagnosis of diaphragmatic hernia based on symptoms after HeartMate 3 implantation and/or subsequent transplantation, as well as the ability to manage these hernias with a minimally invasive laparoscopic approach to minimize postoperative morbidity and mortality.

Malignancy-Associated Non-Bacterial Thrombotic Endocarditis Causing Aortic Regurgitation and Leading to Aortic Valve Replacement.

Described herein is a 48-year-old woman with metastatic ovarian cancer who developed aortic regurgitation considered clinically to be the result of infective endocarditis but operative resection of the three aortic valve cusps disclosed the valve lesions to be typical of non-bacterial thrombotic endocarditis (NBTE). Aortic regurgitation as a consequence of NBTE is rare but at least 9 cases have been reported previously.

Long-term outcomes of patients with primary graft dysfunction after cardiac transplantation.

OBJECTIVES: The International Society of Heart and Lung Transplantation (ISHLT) criteria for primary graft dysfunction (PGD) after cardiac transplantation have been shown to stratify patient outcomes up to 1 year after transplantation, but scarce data are available regarding outcomes beyond the 1st year. We sought to characterize survival of patients with PGD following cardiac transplantation beyond the 1st year. METHODS: A retrospective review of consecutive patients undergoing isolated cardiac transplantation at a single centre between 2012 and 2015 was performed. Patients were diagnosed with none, mild, moderate or severe PGD by the ISHLT criteria. Survival was ascertained from the United Network for Organ Sharing database and chart review. Kaplan-Meier curves were plotted to compare survival. The hazard ratio for mortality associated with PGD severity was estimated using Cox-proportional hazards modelling, with a pre-specified conditional survival analysis at 90 days. RESULTS: A total of 257 consecutive patients underwent cardiac transplantation during the study period, of whom 73 (28%) met ISHLT criteria for PGD: 43 (17%) mild, 12 (5%) moderate and 18 (7%) severe. Patients with moderate or severe PGD had decreased survival up to 5 years after transplantation (log-rank P < 0.001). Landmark analyses demonstrated that patients with moderate or severe PGD were at increased risk of mortality during the first 90-days after transplantation as compared to those with none or mild PGD [hazard ratio (95% confidence interval) 18.9 (7.1-50.5); P < 0.001], but this hazard did not persist beyond 90-days in survivors (P = 0.64). CONCLUSIONS: A diagnosis of moderate or severe PGD is associated with increased mortality up to 5 years after cardiac transplantation. However, patients with moderate or severe PGD who survive to post-transplantation day 90 are no longer at increased risk for mortality as compared to those with none or mild PGD.