Repair of Dissecting Aortic Aneurysm in Post-LVAD Patient.

Left ventricular assist devices (LVAD) are frequently used in the management of end-stage heart failure, especially given the limited availability of donor hearts. The latest HeartMate 3 LVAD delivers non-physiological continuous flow (CF), although the impact on the aorta is not well established. We highlight a case of aortic aneurysm formation complicated by dissection formation that necessitated high-risk re-operative surgery in a patient post CF-LVAD.

Proteomic features of gray matter layers and superficial white matter of the rhesus monkey neocortex: comparison of prefrontal area 46 and occipital area 17.

In this novel large-scale multiplexed immunofluorescence study we comprehensively characterized and compared layer-specific proteomic features within regions of interest of the widely divergent dorsolateral prefrontal cortex (A46) and primary visual cortex (A17) of adult rhesus monkeys. Twenty-eight markers were imaged in rounds of sequential staining, and their spatial distribution precisely quantified within gray matter layers and superficial white matter. Cells were classified as neurons, astrocytes, oligodendrocytes, microglia, or endothelial cells. The distribution of fibers and blood vessels were assessed by quantification of staining intensity across regions of interest. This method revealed multivariate similarities and differences between layers and areas. Protein expression in neurons was the strongest determinant of both laminar and regional differences, whereas protein expression in glia was more important for intra-areal laminar distinctions. Among specific results, we observed a lower glia-to-neuron ratio in A17 than in A46 and the pan-neuronal markers HuD and NeuN were differentially distributed in both brain areas with a lower intensity of NeuN in layers 4 and 5 of A17 compared to A46 and other A17 layers. Astrocytes and oligodendrocytes exhibited distinct marker-specific laminar distributions that differed between regions; notably, there was a high proportion of ALDH1L1-expressing astrocytes and of oligodendrocyte markers in layer 4 of A17. The many nuanced differences in protein expression between layers and regions observed here highlight the need for direct assessment of proteins, in addition to RNA expression, and set the stage for future protein-focused studies of these and other brain regions in normal and pathological conditions.

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.

Multicenter Registry Using Propensity Score Analysis to Compare a Novel Transport/Preservation System to Traditional Means on Postoperative Hospital Outcomes and Costs for Heart Transplant Patients.

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.

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.

Radiolabeled Aminopyrazoles as Novel Isoform Selective Probes for pJNK3 Quantification.

The c-Jun N-terminal kinase 3 (JNK3) is a stress-activated kinase primarily expressed in the brain and implicated as an early mediator of neuronal apoptosis. We sought to develop a PET tracer to visualize pathological JNK3 activation. Because regional JNK3 activation precedes apoptosis, such an imaging agent might enable the detection of "at risk" brain regions prior to neuronal death. We prepared a set of 19F-containing compounds on the basis of the reported aminopyrazoles. The candidate, F3, was tritiated and used in autoradiography experiments to demonstrate regional and temporal changes in JNK3 activation in a mouse model of Parkinson's disease. A significant increase in pJNK3 B max versus control animals in multiple brain regions was observed at 8 months, including the ventral midbrain. Pathological activation of JNK3 in these regions preceded statistically significant neuron loss. Analyses of brain concentrations of [18F]-F3 in naïve rats following intravenous injection revealed a small but detectable signal over the background, but was likely not sufficient to support PET imaging.

Extracorporeal membrane oxygenation for respiratory failure in phases of COVID-19 variants.

BACKGROUND: Adaptive mutations of the severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) virus have emerged throughout the coronavirus disease 2019 (COVID-19) pandemic. The characterization of outcomes in patients requiring extracorporeal membrane oxygenation (ECMO) for severe respiratory distress from COVID-19 during the peak prevalence of different variants is not well known. METHODS: There were 131 patients with laboratory-confirmed SARS-CoV-2 infection supported by ECMO at two referral centers within a large healthcare system. Three predominant variant phase time windows (Pre-Alpha, Alpha, and Delta) were determined by a change-point analyzer based on random population sampling and viral genome sequencing. Patient demographics and outcomes were compared. RESULTS: The average age of patients was 46.9 ± 10.5 years and 70.2% (92/131) were male. Patients cannulated for ECMO during the Delta variant wave were younger compared to earlier Pre-Alpha (39.3 ± 7.8 vs. 48.0 ± 11.1 years) and Alpha phases (39.3 ± 7.8 vs. 47.2 ± 7.7 years) (p < .01). The predominantly affected race in the Pre-Alpha phase was Hispanic (52.2%; 47/90), while in Alpha (61.5%; 16/26) and Delta (40%; 6/15) variant waves, most patients were White (p < .01). Most patients received a tracheostomy (82.4%; 108/131) with a trend toward early intervention in later phases compared to Pre-Alpha (p < .01). There was no significant difference between the duration of ECMO, mechanical support, intensive care unit (ICU) length of stay (LOS), or hospital LOS over the three variant phases. The in-hospital mortality was overall 41.5% (54/131) and was also similar. Six-month survival of patients who survived to discharge was 92.2% (71/77). CONCLUSIONS: There was no significant difference in survival or time on ECMO support in patients during the peak prevalence of the three variants.

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.