Background:Acute cellular rejection (ACR) remains a major cause of morbidity after heart transplantation despite advances in immunosuppression. Whole genome transcriptomic profiling offers a systems-based, unbiased approach to elucidate the molecular mechanisms underlying ACR. However, noninvasive, longitudinal biomarker assessments capable of capturing the temporal dynamics of rejection biology remain scarce. Methods:RNA sequencing of peripheral blood from heart transplant recipients before, during, and after ACR was compared with nonrejection controls. Pathway analysis was conducted using differentially expressed genes (DEGs), and a machine learning approach was applied to assess gene-based prediction of ACR. Results:A total of 235 rejection-specific significant DEGs and 863 postrejection DEGs (false discovery rate < 0.05) were identified. During ACR, DEGs were enriched for T-cell activation/differentiation, apoptosis, and B-cell receptor signaling pathways. By combining the 2 sets of DEGs, a panel of 71 common genes was identified that reflected the significant, longitudinal transcriptomic dynamics of ACR. In an elastic net machine learning-based classifier, DYNLL1 and SERF2 were identified as ACR predictive genes, and achieved a cross-validated area under the receiver operating characteristic curve of 0.63. Conclusions:Peripheral blood transcriptomics identify dynamic temporal responses in ACR including T- and B-cell pathways with potential ACR predictive genes that warrant further investigation.

BACKGROUND:The prognosis in patients with advanced cardiac amyloidosis (CA) remains poor. OBJECTIVES:We sought to describe survival post heart transplantation (HT) in amyloid compared with non-amyloid recipients, highlight waitlist times within the new allocation system across three Organ Procurement and Transplantation Network (OPTN) regions, and describe multiorgan transplantation (MOT) in hereditary amyloidosis. METHODS:This is a retrospective review of end-stage CA patients who underwent HT at Mayo Clinic from January 2007 to December 2020. Wait time was compared in the new versus old OPTN allocation era starting December 18, 2018 by Wilcoxon rank sum test. All-cause mortality for those with and without CA was compared using Kaplan-Meier estimates with log rank analysis, censoring December 16, 2022. RESULTS:Fifty-five patients with CA underwent HT between 2007 and 2020, 8 light chain amyloidosis (AL) (14.5%), 28 hereditary transthyretin (ATTRv) (50.9%), 17 wildtype transthyretin (ATTRwt) (30.9%), and 2 hereditary apolipoprotein A1 (AApoA1) amyloidosis patients (3.6%). No significant difference in overall survival post-transplant was seen in amyloid compared with non-amyloid (p = 0.816). Median time to HT was shorter in the new system, 45 days (IQR 24, 78) versus 174 days (IQR 76.5, 483.5), p = 0.006. There was a decline in MOT in hereditary amyloidosis over time with the concomitant rise in disease-targeted therapies. CONCLUSIONS:HT survival in CA patients was similar to non-amyloid patients. The new allocation system benefits this cohort with shorter wait times. There is less MOT in hereditary amyloidosis with increased utilization of disease-targeted therapy.

BackgroundEmotional Affect reflects an individual’s emotional state and can be categorized as positive (PA) or negative (NA). We aimed to characterize affect in heart transplant candidates and evaluate its relationship with pre- and post-transplant psychological and clinical outcomes.MethodsUsing the Positive and Negative Affect Schedule (PANAS), we surveyed adult heart transplant candidates across three transplant centers at baseline (waitlist enrollment), annually on the waitlist, and post-transplant. We assessed PA, NA, and the positivity ratio (PR; PA/NA) as potential predictors of waitlist mortality, post-transplant hospital length of stay, readmissions, and quality of life.ResultsAmong 194 participants, the majority were male (68.6%) and Caucasian (84.3%). Baseline PA (36.0 ± 7.8) and NA (17.9 ± 6.4) were comparable to population norms and remained stable over time. PR was low at baseline (2.3 ± 1.0) and decreased post-transplant (−0.3 ± 1.2; p = 0.03). PA decreased and NA increased post-transplant, but neither change was statistically significant. Affect was not associated with waitlist mortality, delisting, length of stay, or readmissions, but baseline PANAS scores correlated with multiple domains of post-transplant quality of life.ConclusionHeart transplant candidates exhibit a suboptimal PR, which declines post-transplant, highlighting significant psychological stress. Pre-transplant PANAS scores correlated with post-transplant quality of life, suggesting a potential role for psychological screening and intervention in transplant care.

BACKGROUND:Patients with end-stage heart failure and chronic kidney disease requiring dual-organ transplantation (DOT) face significant challenges in utilizing durable mechanical circulatory support due to the risks associated with renal replacement therapies (RRTs) and multi-organ failure. Given the limited options available for long-term support in this patient population, there remains a critical need for alternative strategies to optimize end-organ function and bridge patients safely to transplant. With prolonged waitlist times for DOT, we present our experience with the Impella 5.5 as temporary mechanical circulatory support, demonstrating its potential to provide hemodynamic stability and support as a bridge to transplantation (BTT) in this complex cohort. METHODS:A single-centre retrospective review was completed of all patients listed for single-organ transplantation or DOT between December 2019 and November 2022 at Mayo Clinic in Florida, supported by the Impella 5.5 intended as BTT. The focus of this analysis was patients requiring RRT or listed for heart/kidney transplantation. Data were extracted from the electronic health record at baseline and during their transplant episode of care after institutional review board approval as exempt status for retrospective data collection. RESULTS:A total of 41 patients were supported with Impella 5.5, intended as BTT. All patients underwent successful transplantation. We focus on the 10 patients with Impella support who underwent DOT. In the DOT group, the median age at transplantation was 63 years (59-66), with nine males and one female. The baseline median ejection fraction was 19% (15-22), with 50% Caucasian and 50% African American and an even split between ischaemic and non-ischaemic aetiology. Median body mass index was 30 kg/m2 (26-31), and 60% were in blood group O. The median time on the waitlist for DOT patients was 53 days (29-75). Perioperative management of DOT Impella patients demonstrated baseline haemodynamics of RA 11 mmHg (7-16), mean PA 36 mmHg (32-47), PCWP 29 mmHg (21-35), mixed venous saturation (SVO2%) 51 (46-61) and Fick CI 2.03 L/min/m2 (1.66-2.5). Post-Impella placement haemodynamics demonstrated significant improvements in RA pressure to 5 mmHg (4-8), P = 0.02, SVO2 to 70% (65-72), P = 0.002, and Fick CI to 5.5 (5.2-8), P = 0.03. The average duration of support was 44 days (range 10-94). The median glomerular filtration rate at baseline was 27 mmol/L (16-29). Twenty-four hour urine protein averaged 168 mg/24 h (range 87-328), with the 24 h creatinine clearance of 29 mg/24 h (range 24-35). Eight of the 10 patients required continuous or intermittent RRT before DOT. The median total duration of RRT (including Impella support) was 36 days (9-72). DOT recipients had a 1 year survival of 90%, with an average follow-up of 432 days. CONCLUSIONS:Our findings demonstrate that prolonged use of the Impella 5.5 provides safe and effective haemodynamic support for patients with end-stage heart and kidney failure awaiting dual-organ transplantation. With a 1 year survival rate of 90%, our data suggest that Impella 5.5 can be a viable alternative to traditional support strategies, particularly in patients who are otherwise limited by RRTs. As dual-organ transplantation becomes more prevalent, the Impella 5.5 offers a promising bridge to transplant, improving both short-term and long-term outcomes in this complex patient population.

Background Stiff left atrial syndrome is a well-established cause of heart failure symptoms. A parallel entity involving the right atrium (RA) has not previously been described. We present a case of refractory right heart failure (RHF) 12 years following orthotopic heart transplantation.Case summary Patient underwent annuloplasty ring placement for severe tricuspid regurgitation in 2018 and kidney transplantation in 2020. The use of multimodality imaging and a multidisciplinary approach suggested a stiff RA as a potential etiology to refractory symptoms. Redo-heart and kidney transplantation in March 2021 led to the resolution of symptoms without recurrence.Discussion We propose stiff right atrial syndrome that may need to be considered in the setting of refractory RHF primarily suggested by significant right atrial enlargement and restrictive physiology.

Background: Decreased systemic oxygen delivery derived from gas exchange abnormalities in severe hemolysis complicates patients requiring mechanical circulatory support devices. Severe hemolysis releases free hemoglobin in plasma causing elevation of carboxyhemoglobin and methemoglobin levels. Hemolysis-induced decline in hemoglobin and oxyhemoglobin saturation significantly reduces the arterial oxygen content in blood, reducing systemic oxygen delivery. These patients develop hypoxemia with misleadingly normal oxygen saturation measured by standard pulse oximetry. Methods: Retrospective review of 2 clinical cases reaching carboxyhemoglobin and methemoglobin levels > 2% while supported with an Impella device. Results: Case 1. Patient with cardiogenic shock refractory to maximal medical therapy required insertion of Impella device achieving improvement in cardiac output, pulse oximetry, arterial oxygen saturation and systemic oxygen delivery. The device caused significant hemolytic anemia with severe decline in hemoglobin and arterial oxygen saturation with elevation of carboxyhemoglobin and methemoglobin levels, causing drastic reduction in systemic oxygen delivery despite adequate cardiac output. Device removal reversed severe hemolytic anemia, causing increased arterial oxygen saturation and systemic oxygen delivery despite borderline cardiac output.Case 2. Patient with refractory cardiogenic shock improved after insertion of Impella device. Initial improvement cardiac output and systemic oxygen delivery was negated by hemolytic anemia associated with elevation of carboxyhemoglobin and methemoglobin levels. Hemolysis decreased by reducing the Impella power output. Carboxyhemoglobin and methemoglobin levels correlated precisely with degree of hemolysis allowing to titrate therapy to best systemic oxygen delivery. Conclusions: Monitoring carboxyhemoglobin and methemoglobin levels readily identifies patients with ongoing hemolysis secondary to invasive supportive devices.

Umadat, Goyal; Lee, Jennifer; Rice, Bria; Gharacholou, Shahyar; Patel, Parag; Yip, Daniel; Leoni, Juan; Lyle, Melissa; Nativi, Jose; Goswami, Rohan Author Information

We sought to investigate the outcomes of heart transplant patients supported with Impella 5.5 temporary mechanical circulatory support.

Background: After the 2018 UNOS organ allocation change, temporary mechanical circulatory support (tMCS) has increased in managing acute decompensated heart failure (ADHF) as a bridge to transplant, recovery, or durable VAD. However, patients supported with tMCS are more prone to complications. Deep venous thrombosis (DVT) is one of the most common complications in this patient population. DVT is associated with an increased risk of pulmonary embolism, stroke, chronic venous insufficiency, and increased length of hospital stays. We aimed to identify the incidence of DVT in ADHF patients supported with tMCS. Method: We performed a retrospective review of patients with ADHF who had undergone heart or heart/kidney transplantation between January 2021 and November 2022 at Mayo Clinic in Florida. Patient data were extracted from the electronic health record after IRB approval as exempt for retrospective chart review was obtained. Our primary outcome was DVT during the transplant, diagnosed by venous duplex ultrasonography. Results: 93 patients with ADHF were found during our review period, of which 46 (49%) developed a DVT. The median age was 60 years (53 – 67), with 65% male. All but one DVT was in the upper extremity. Within the DVT population, 75% were hypertensive (p <.001), 64% were diabetic (p =.003), 78% had hyperlipidemia (p<.001), and had elevated mean creatinine of 2.16 vs. 1.55 (p =.04). A total of 44 patients required tMCS, of these, 26 patients developed DVT (59%) which was statistically significant compared to 18 that did not develop DVT while on tMCS, p =.04. The combination of support was as follows: 27 axillary Impella 5.5 alone, 5 VA ECMO without LV vent, 1 VA ECMO with IABP vent, 4 VA ECMO with Impella 5.5 vent, and 7 intra-aortic balloon pumps only. Ischemic cardiomyopathy was not a significant risk for DVT, p =.372. The median ejection fraction was 25% (15 -55). The median LOS was 48 days (31 – 74). Patients with DVT were found to have a significantly lower BMI, 26.4 vs 29.3 (p =.002), as well as a significantly shorter cardiopulmonary bypass time of 187min vs. 296 min (p <.001). Conclusions: We found increased rates of DVT in patients utilizing all forms of tMCS with ADHF. Factors influencing the development of DVT may relate to an overall increased inflammatory state, evidenced by our data showing significant differences in rates of hypertension, diabetes, hyperlipidemia, worse renal function, and sarcopenia. Chronicity of disease, time in the hospital, and the need for more procedures may also influence DVT risk in patients awaiting transplantation or LVAD.

Donation after circulatory death (DCD) is becoming increasingly utilized in heart transplantation and has the potential to further expand the donor pool. As transplant cardiologists gain more familiarity with DCD donor selection, there are many issues that lack consensus including how we incorporate the neurologic examination, how we measure functional warm ischemic time (fWIT), and what fWIT thresholds are acceptable. DCD donor selection calls for prognostication tools to help determine how quickly a donor may expire, and in current practice there is no standardization in how we make these predictions. Current scoring systems help to determine which donor may expire within a specified time window either require the temporary disconnection of ventilatory support or do not incorporate any neurologic examination or imaging. Moreover, the specified time windows differ from other DCD solid organ transplantation without standardization or strong scientific justification for these thresholds. In this perspective, we highlight the challenges faced by transplant cardiologists as they navigate the muddy waters of neuroprognostication in DCD cardiac donation. Given these difficulties, this is also a call to action for the creation of a more standardized approach to improve the DCD donor selection process for appropriate resource allocation and organ utilization.

Background: Pulmonary hypertension (PH) is associated with advanced heart failure, which results in a worse prognosis, limits candidacy for heart transplant (HTx), and increases complications after HTx. Heart/lung transplant may overcome the complications of PH. However, the survival duration of patients after dual organ transplant is significantly shorter than HTx alone. We present a case of cardiogenic shock and severe PH in which we used temporary mechanical circulatory support with an Impella 5.5 to optimize PH successfully. Case: A 54-year-old female blood group O after workup and review by our selection committee was listed as status 6 for HTx due to non-ischemic cardiomyopathy. Right heart catheterization showed an RA of 15 mmHg, PA 75/37 (50), and PCWP 32. The Fick cardiac index was 1.2L/min/m2 with a PA saturation of 52% and PVR of 5.2 WU. On 3mcg/kg/min of Nipride, mPA was 38, and PCWP of 26. Concern for progression to fixed PH despite milrinone led our team to proceed with Impella 5.5 placement. Her PH improved after Impella to PA 51/15 (27) and PCWP of 15 with a PVR of 2.7 WU. She underwent a successful HTx and remains alive at 2 years without recurrent pulmonary hypertension. Decision-making: In a complex patient with WHO class II PH (unrelated to mitral valve disease), therefore not a candidate for therapies such as MitraClip, LV unloading is known to optimize multi-organ function and reduce PH. Traditionally the inability of sustained reversal of PH (mPA <40, PVR <3.5wu) with medical management is a contraindication for HTx. Given our patient’s choice to decline LVAD placement, our heart team felt it prudent to use the Impella 5.5 in an attempt to unload the LV fully. Conclusion: Our case shows the potential impact the Impella 5.5 device can have on patients with severe pulmonary hypertension. The implication of this therapy in avoiding heart/lung transplant, and potentially improving survival, should be explored.

Objective To determine the effectiveness of communication training and its impact on burnout among healthcare providers (physicians, physician assistants, nurse practitioners), in the setting of the COVID-19 pandemic. Methods To evaluate the effectiveness of communication training on burnout during the COVID-19 pandemic, healthcare providers participating in a Communication in Healthcare (CIH) module between October 31, 2019, through February 20, 2020, were identified using a scanned sign-in sheet. A 3-question online survey regarding the utilization of communication skills during the COVID-19 pandemic was sent via email. An ordinal scale was used to rate the effectiveness of the training on subsequent burnout and work satisfaction during the pandemic. Results Of the 98 surveys distributed via email, a total of 33 participants completed the survey. Seventy-three percent of respondents agreed that communication training helped prevent burnout, and 39% strongly agreed that the modules improved work satisfaction. Conclusion Our study found communication training was effective in reducing burnout in healthcare providers, in the setting of the COVID-19 pandemic. The participants felt the communication tools learned from the training modules were useful in improving work satisfaction and communication with patients during the pandemic.

Impaired kidney function is often associated with acute decompensation of chronic heart failure and portends a poor prognosis. Unfortunately, current data have demonstrated worse survival in patients with acute kidney injury than in patients with chronic kidney disease during durable LVAD placement as bridge therapy. Furthermore, end-stage heart failure patients undergoing combined heart-kidney transplantation have poorer short- and long-term survival than heart transplants alone. We evaluated the kidney function recovery in our heart failure population awaiting heart transplantation at our institution, supported by temporary Mechanical Circulatory Support (tMCS) with Impella 5.5. The protocol (#22004000) was approved by the Mayo Clinic institutional review board, after which we performed a retrospective review of all patients with acute on chronic heart failure and kidney disease in patients considered for only heart and kidney combined organ transplant and supported by tMCS between January 2020 and February 2021. Hemodynamic and kidney function trends were recorded and analyzed before and after tMCS placement and transplantation. After placement of tMCS, we observed a trend towards improvement in creatinine, Fick cardiac index, mixed venous saturation, and glomerular filtration rate (GFR), which persisted through transplantation and discharge. The average duration of support with tMCS was 16.5 days before organ transplantation. The median pre-tMCS creatinine was 2.1 mg/dL (IQR 1.75–2.3). Median hematocrit at the time of tMCS placement was 32% (IQR 32–34), and the median estimated glomerular filtration rate was 34 mL/min/BSA (34–40). The median GFR improved to 44 mL/min/BSA (IQR 45–51), and serum creatinine improved to 1.5 mg/dL (1.5–1.8) after tMCS. Median discharge creatinine was 1.1 mg/dL (1.19–1.25) with a GFR of 72 (65–74). None of these six patients supported with tMCS required renal replacement therapy after heart transplantation. Early adoption of Impella 5.5 in this patient population resulted in renal recovery without needing renal replacement therapies or dual organ transplantation and should be further evaluated.

BACKGROUND Optimizing patients with advanced heart failure before orthotopic heart transplantation (OHT), especially in patients greater than 50 years old, is imperative to achieving successful post-transplant outcomes. Complications are well-described for patients bridged to transplant (BTT) with durable left ventricular assist device (LVAD) support. Given the lack of data available in older recipients after the recent increase in mechanical support use, we felt it crucial to report our center's one-year outcomes in older recipients after heart transplantation with percutaneously placed Impella 5.5 as a BTT. METHODS Forty-nine OHT patients were supported with the Impella 5.5 intended as a bridge between December 2019 and October 2022 at Mayo Clinic in Florida. Data were extracted from the electronic health record at baseline and during their transplant episode of care after Institutional Review Boards approval as exempt for retrospective data collection. RESULTS Thirty-eight patients aged 50 or older were supported with Impella 5.5 as BTT. Ten patients underwent heart and kidney transplantation within this cohort. The median age at OHT was 63 (58-68) years, with 32 male (84%) and six female patients (16%). Etiology was divided into ischemic (63%) and non-ischemic cardiomyopathy (37%). The baseline median ejection fraction was 19% (15-24). Most patients were in blood group O (60%), and 50% were diabetic. The average duration of support was 27 days (range 6-94). The median duration of follow-up is 488 days (185-693). For patients that have reached the 1-year follow-up timeframe (22 of 38, 58%), the 1-year post-transplant survival is 95%. CONCLUSION Our single-center data provides awareness for using the Impella 5.5 percutaneously placed axillary support device in older heart failure patients in cardiogenic shock as a bridge to transplantation. One-year survival outcomes after heart transplantation are excellent despite the older recipient's age and prolonged pre-transplant support.

BACKGROUND:We aimed to investigate the short-term outcomes of heart transplant patients who underwent SherpaPak™ donor organ preservation.METHOD:We prospectively collected the data of patients who underwent heart transplantation using SherpaPak™ system for donor organ transportation from February 2020 to March 2021. Donor and recipient demographic data, preoperative and postoperative echocardiographic and hemodynamic parameters, total ischemic time and SherpaPak temperatures, vasoactive inotropic scores (VIS), primary graft dysfunction (PGD) status, intensive care unit stay, complications, and mortality during follow-up were assessed.RESULTS:A total of 39 consecutive heart transplant patients with SherpaPak system were included in the study. The mean donor age was 32.2 ± 6.7 (range: 16-46). The mean recipient age was 57.5 ± 12 (range: 19-73). The mean preoperative ejection fraction (EF) was 23.7 ± 15.4 (range: 5-75). All recipients underwent a standard bicaval technique for orthotopic heart implantation. The mean total ischemic time was 230.1 ± 41 (range: 149-342) min. The mean Sherpa temperature was 5.6 ± 0.8°C (range: 3.7-7.5). The mean VIS was 10.2 ± 6.5 (range: 2-32). The number of mild PGD was 5 (14.7%), and moderate PGD was 4 (11.8%). There was no severe PGD. The postoperative EF was 64.3 ± 5.5 (range: 50-78). Mean intubation time was 47.4 ± 64 (range: 8-312, median: 22) h. The mean time of intensive care unit stay was 6.3 ± 5 (range: 2-31, median: 5) days. Two patients required chest revision (5.8%), two patients had lung infection (5.8%). Two patients had a stroke (5.8%). There was no mortality.CONCLUSION:Using the SherpaPak system during heart transplantation is safe and not associated with significant recipient morbidity. None of the recipients experienced significant PGD and mortality.

INTRODUCTION:The present study aimed to compare the clinical outcomes of heart transplant patients whose donor hearts were preserved with the SherpaPak controlled cold organ system versus the conventional ice storage technique.METHODS:All patients undergoing heart transplantation at our center between January 2019 and April 2021 were divided into two groups according to the technique used during donor heart preservation and transport. The first group consisted of 34 SherpaPak controlled temperature preservation patients, and the second group consisted of 47 patients where the conventional three bags and ice technique was utilized during organ transportation. The two groups were compared based on demographics, operative details, and postoperative outcomes.RESULTS:There were no significant differences between the groups regarding Vasoactive Inotropic Score (VIS), Primary Graft Dysfunction (PGD), and the need for a transient pacer. However, the VIS, PGD, and pacing trends were lower in the SherpaPak patients even though the total ischemic and cardiopulmonary bypass times were significantly longer. Furthermore, SherpaPak patients exhibited a shorter stay in the ICU with no severe PGD and mortality.CONCLUSION:The SherpaPak donor heart preservation provides safe outcomes in heart transplant patients. Further research is needed to utilize this method for longer durations of ischemic time and expand travel distances for organ transportation.