Faculty Bibliography

Left ventricular assist devices (LVAD) are surgically implanted mechanical support devices utilized with increasing frequency as a bridge to myocardial recovery, destination therapy, and heart transplantation. While the use of such devices in patients with advanced heart failure has shown significant survival benefits and improved quality of life, they bear their own risks and complications.¹ Bleeding, infection, pump thrombosis, and stroke are just some of the serious complications associated with LVADs.² LVAD-associated pseudoaneurysms are rare, with prior reports of occurrence at the left ventricular apex and at the anastomosis site of the outflow graft to the ascending aorta.^3,4 Typically, this device-related complication requires surgical repair and, if at all feasible, heart transplantation. However, in cases of difficult anatomy, unfavorable position, and significant comorbidities, surgery may be contraindicated due to high surgical risk. This case portrays a patient suffering from a left ventricular pseudoaneurysm after HeartMate-III implantation that was not amenable to surgical repair due to heightened surgical risk. We document the first pseudoaneurysm associated with the HeartMate-III in available literature and describe a novel management strategy of documented nonoperative course of LVAD-associated pseudoaneurysm, with the patient surviving 56+ months with medical optimization and management.

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.

Despite advances in medical therapy for patients with stage C heart failure (HF), survival for patients with advanced HF is <20% at 5 years. Durable left ventricular assist device (dLVAD) support is an important treatment option for patients with advanced HF. Innovations in dLVAD technology have reduced the risk of several adverse events, including pump thrombosis, stroke, and bleeding. Average patient survival is now similar to that of heart transplantation at 2 years, with 5-year dLVAD survival now approaching 60%. Unfortunately, greater adoption of dLVAD therapy has not been realized due to delayed referral of patients to advanced HF centers, insufficient clinician knowledge of contemporary dLVAD outcomes (including gains in quality of life), and deprioritization of patients with dLVAD support waiting for heart transplantation. Despite these challenges, novel devices are on the horizon of clinical investigation, offering smaller size, permitting less invasive surgical implantation, and eliminating the percutaneous lead for power supply.

Del Nido cardioplegia offers equivalent myocardial protection and clinical outcomes to blood cardioplegia in adult isolated CABG and valve patients, but the safety and efficacy of del Nido in complex cases with prolonged aortic cross-clamp times is still unknown. 443 patients at our center underwent replacement of the ascending aorta using either del Nido (n = 182) or blood (n = 261) cardioplegia. Two surgeons used del Nido exclusively and 6 used blood exclusively over the study period. Propensity matching of preoperative characteristics yielded 172 well matched pairs. Emergency and reoperative cases were included. Clinical data were extracted from our local database. Troponin levels were drawn at 12 hours postop in all patients. Rates of perioperative mortality (4.7% vs 5.2%), stroke (5.8% vs 7.0%), renal failure (11.6% vs 12.2%), atrial fibrillation (36.0% vs 31.4%), intra-aortic balloon pump insertion (2.3% vs1.2%), and extra corporeal membrane oxygenation use (4.7% vs 4.1%) did not differ between blood and del Nido groups. Postop Troponin T levels were 0.50[0.35, 0.86] ng/mL and 0.40[0.20, 0.70] ng/mL for blood and del Nido, respectively (P < 0.0001). Postop echocardiography was available in 333 of 344 (96.8%) patients, and there was no difference in change in EF from pre- to postop between blood 0.0[-6.0, 5.0]% and del Nido 0.0 [-6.0, 3.5]% (P = 0.201). Subgroup analysis of patients with aortic cross-clamp time greater than 180 minutes (blood = 77, del Nido = 27) revealed no difference in troponins, ejection fraction, or clinical outcomes. Five-year survival was 85.9[76.8, 91.7]% and 79.8[71.2, 86.1]% for blood and del Nido, respectively (P = 0.151). In ascending aortic surgery with prolonged operative times, no differences were observed in myocardial protection or clinical outcomes with the use of del Nido cardioplegia compared to blood cardioplegia.

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.

BACKGROUND:Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a key support modality for cardiogenic shock. The 2018 United Network for Organ Sharing (UNOS) heart transplant allocation algorithm prioritizes VA-ECMO patients. OBJECTIVE:To evaluate the role of VA-ECMO in bridging to advanced heart failure therapies. METHODS:We analyzed adult patients from the multicenter Extracorporeal Life Support Organization registry receiving VA-ECMO for cardiac support or resuscitation between 2016 and 2021 in the United States, comparing bridge-to-transplant (BTT) and non-BTT intent patients, as well as pre- vs post-2018 patients, on a wide range of demographic and clinical outcome predictors. RESULTS:Of 17,087 patients, 797 received left ventricular assist device (LVAD)/heart transplant, 7,931 died or had poor prognosis, and 8,359 had expected recovery at ECMO discontinuation. Patients supported with BTT intent had lower clinical acuity than non-BTT candidates and were more likely to receive LVAD/transplant. The proportion of patients who received VA-ECMO as BTT and received LVAD/transplant increased after 2018. Post-2018 BTT patients had significantly lower clinical acuity and higher likelihood of transplant than both post-2018 non-BTT patients and pre-2018 BTT patients. ECMO complications were associated with lower likelihood of transplant but were significantly less common post-2018 than pre-2018. CONCLUSIONS:After implementation of the 2018 UNOS allocation system, ECMO utilization as BTT or LVAD has increased, and the acuity of BTT intent patients cannulated for ECMO has decreased. There has not yet been an increase in more acute ECMO patients getting transplanted. This may partially explain the post-transplant outcomes of ECMO patients in the current era reported in UNOS.

INTRODUCTION:Acute kidney injury (AKI) in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is associated with high mortality. The objective of this study was to investigate whether cytokine levels before the initiation of ECMO treatment could predict AKI. We also aimed to investigate the impact of AKI on 30-day and 1-year mortality. METHODS:Serum cytokine levels were analyzed in 100 consecutive VA-ECMO-treated patients at pre-cannulation, at 48 h post-cannulation, and at 8 days. Clinical data to establish the incidence and outcome of AKI after the start of ECMO was retrieved from the local ECMO registry. SETTING:The study was conducted at tertiary care, university hospital. Participants included 100 patients treated with VA-ECMO. INTERVENTIONS:The blood samples for cytokine analysis were collected before VA-ECMO treatment, at 48 h after VA-ECMO treatment was started, and at 8 days. RESULTS:Pre-cannulation serum IL-10 levels were significantly higher in patients who developed AKI (212 [38.9, 620.7]) versus those who did not (49.0 [11.9, 102.2]; p = 0.007), and the development of AKI can be predicted by pre-cannulation IL-10 levels (p = 0.025, OR = 1.2 [1.02-1.32]). The development of AKI during ECMO treatment is associated with increased 30-day mortality (p = 0.049) compared to patients who did not develop AKI and had a pre-cannulation estimated glomerular filtration rate ≥ 45 mL/min. The 1-year survival rate for patients with AKI who survived the first 30 days of ECMO treatment is comparable to that of patients without AKI. CONCLUSION:Increased pre-cannulation IL-10 levels are associated with the development of AKI during VA-ECMO support. AKI is associated with increased 30-day mortality compared to patients with no AKI and better renal function. However, patients with AKI who survive the first 30 days have a 1-year survival rate similar to those without AKI.

The standard method for cardiac allograft preservation for the past 50 years has been static storage using crushed ice. A heart transplant transportation system designed to improve preservation quality with temperature monitoring, the Paragonix SherpaPak Cardiac Transport System (SCTS), was evaluated for its impact on postoperative costs relative to conventional ice storage. Observational US multicenter registry data collected during the August 2015 to November 2021 timeframe from 12 transplant hospitals were analyzed using logistic regression analysis and propensity matching to balance measured baseline covariates and to reduce selection bias. Hospital cost and outcome data post-transplant were then evaluated using various statistical methods. One hundred seventy-four (174) patients were identified resulting in 87 matches. Baseline characteristics were similar between groups. The SCTS group had a significantly lower proportion of ICU days on post-transplant mechanical circulatory support ( p < 0.0001); significantly fewer patients on extracorporeal membrane oxygenation ( p = 0.017); and significantly fewer patients experiencing severe primary graft dysfunction (PGD) ( p = 0.03). Overall hospital plus mechanical circulatory support post-transplant costs were significantly lower by $26.7K in the CTS cohort ( p = 0.03). Use of the SCTS is associated with improved clinical outcomes resulting in significantly lower overall hospital care costs.

PURPOSE:To evaluate the effect of the new heart transplant (HT) allocation system in left ventricular assist device (LVAD) supported patients listed as bridge to transplantation (BTT). METHODS:Adult patients who were listed for HT between October 18, 2016 and October 17, 2019, and were supported with an LVAD, enrolled in the UNOS database were included in this study. Patients were classified in the old or new system if they were listed or transplanted before or after October 18, 2018, respectively. RESULTS:A total of 3261 LVAD patients were listed for transplant. Of these, 2257 were classified in the old and 1004 in the new system. The cumulative incidence of death or removal from the transplant list due to worsening clinical status at 360-days after listing was lower in the new system (4% vs. 7%, P = .011). LVAD Patients listed in the new system had a lower frequency of transplantation within 360-days of listing (52% vs. 61%, P < .001). A total of 1843 LVAD patients were transplanted, 1004 patients in the old system and 839 patients in the new system. The post-transplant survival at 360 days was similar between old and new systems (92.3% vs. 90%, P = .08). However, LVAD patients transplanted in the new system had lower frequency of the combined endpoint, freedom of death or re-transplantation at 360 days (92.2% vs. 89.6%, P = .046). CONCLUSION:The new HT allocation system has affected the LVAD-BTT population significantly. On the waitlist, LVAD patients have a decreased cumulative frequency of transplantation and a concomitant decrease in death or delisting due to worsening status. In the new system, LVAD patients have a decreased survival free of re-transplantation at 360 days post-transplant.

Historically, adult congenital patients have longer waitlist time and worse outcomes on the heart transplant waitlist as well as poorer early post-transplant survival. A new heart transplantation allocation system was implemented in the United States on October 18, 2018. The effect of the new allocation system on adult congenital patients is unknown. Adult congenital patients listed for transplantation between November 1, 2015 and September 30, 2019 registered in the United Network for Organ Sharing were included in the study. October 18, 2018 was used as the limit to distribute listed and transplanted patients into old and new groups. A total of 399 patients were listed for heart transplant only, 284 in the old system and 115 in the new system. Clinical characteristics were similar between both groups. The cumulative incidence of poor outcome on the transplant list was similar in both groups (P = .23), but the cumulative incidence of transplant was higher in the new system group (P < .009) and was associated with a shorter waitlist time. The one-year post-transplant outcome was similar between old and new groups (P = .37). The new allocation system has benefited adult congenital patients with increased cumulative frequency of transplantation without worsening short-term survival after transplantation.