Adult Congenital Heart Disease Transplantation: Does Univentricle Physiology Impact Early Mortality?

BACKGROUND: With congenital heart disease patients increasingly living into adulthood, there is a growing population of adult congenital heart disease (ACHD) patients suffering from heart failure. Limited data exist evaluating heart transplant in this population. METHODS: Retrospective review was performed of ACHD patients undergoing heart transplantation 11/1990-1/2023. Kaplan-Meier, cumulative incidence accounting for competing risk of death, and subgroup analyses comparing those with biventricular (BiV) and univentricular (UniV) physiology were performed. Data are presented as median (interquartile range) or counts (%). RESULTS: 77 patients with a median age of 36 years (27, 45) were identified, including 57 (74%) BiV and 20 (26%) UniV. Preoperatively, UniV patients were more likely to have cirrhosis (9/20 [45.0%] vs 4/57 [7.0%], p<0.001) and protein losing enteropathy (4/20 [20.0%] vs 1/57 [1.8%], p=0.015). Multiorgan transplantation was performed in 23 patients (30%) and more frequently in UniV patients (10 [50%] vs. 13[23%], p=0.04). Operative mortality was 6.5%, 2/20 (10%) among UniV and 2/57 (4%) among BiV patients, p=0.276. Median clinical follow-up was 6.0 (1.4, 13.1) years. Survival tended to be lower among UniV patients compared to BiV patients, particularly within the first year (p=0.09), but was similar for survivors beyond one year. At 5 years, incidence of rejection was 28% (17%, 38%) and coronary allograft vasculopathy was 16% (7%, 24%). CONCLUSIONS: Underlying liver disease and need for heart/liver transplantation were significantly higher among UniV patients. Survival tended to be lower among UniV, particularly within the first year, but was similar for survivors beyond one year.

Novel Left Ventricular Unloading Strategies in Patients on Peripheral Venoarterial Extracorporeal Membrane Oxygenation Support.

The purpose of this study was to evaluate left ventricular (LV) unloading strategies in patients supported with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). A retrospective review was conducted of all consecutive patients requiring VA-ECMO support for any indication, who underwent novel LV unloading strategies with either direct left atrial venoarterial (LAVA) cannulation or pulmonary artery venoarterial (PAVA) venting, in comparison to Impella and intra-aortic balloon pump (IABP). The primary outcome was successful bridge to transplant, LV assist device, or myocardial recovery. Forty-six patients (63% male, mean age 52.8 ± 17.6 years) were included. Fourteen patients (30%) underwent novel unloading with either LAVA or PAVA, 11 patients (24%) underwent IABP placement, and 21 patients (46%) underwent Impella insertion. In the novel LV unloading cohort, 10 patients (71%) survived to hospital discharge. Four patients (29%) were weaned from ECMO and eight patients (57%) underwent cardiac transplantation. Although a trend favoring cannula-based unloading for the primary outcome was noted, the cohort was too small for statistical significance (79% LAVA/PAVA, 57% Impella, 45% IABP; p = 0.21). However, probability of survival was greater in the LAVA/PAVA cohort compared to Impella and IABP ( p < 0.05). Thus, we demonstrate the efficacy of LA and PA cannulation as an alternative LV unloading strategy for patients supported with peripheral VA-ECMO.

Obesity and Extracorporeal Membrane Oxygenation (ECMO): Analysis of Outcomes.

Traditionally, patients with obesity have been deemed ineligible for extracorporeal life support (ELS) therapies such as extracorporeal membrane oxygenation (ECMO), given the association of obesity with chronic health conditions that contribute to increased morbidity and mortality. Nevertheless, a growing body of literature suggests the feasibility, efficacy, and safety of ECMO in the obese population. This review provides an in-depth analysis of the current literature assessing the effects of obesity on outcomes among patients supported with ECMO (venovenous [VV] ECMO in noncoronavirus disease 2019 and coronavirus disease 2019 acute respiratory distress syndrome, venoarterial [VA] ECMO, and combined VV and VA ECMO), offer a possible explanation of the current findings on the basis of the obesity paradox phenomenon, provides a framework for future studies addressing the use of ELS therapies in the obese patient population, and provides guidance from the literature for many of the challenges related to initiating, maintaining, and weaning ELS therapy in patients with obesity.

Heart-Lung Transplantation From Donation After Circulatory Death Using Mobile Normothermic Regional Perfusion.

Combined heart-lung transplant (HTLx) is the most durable treatment available for end-stage heart and lung failure. Many patients are unable to receive combined organs due to organ availability and allocation policies prioritizing separate heart or lung transplantation. While an average of 45 HTLxs have been performed per year in the United States half the listed patients do not receive organs. Recently, donation after circulatory death (DCD) utilizing normothermic regional perfusion (NRP) has been utilized for heart allografts with excellent results, and here, we present a case utilizing mobile NRP to procure a heart and lung block from a circulatory death donor and successful implantation for a recipient in a separate center.

Inhibition of angiogenesis in the management of refractory gastrointestinal bleeding in patients with LVAD support.

BACKGROUND: Gastrointestinal bleeding (GIB) in patients with continuous flow left ventricular assist devices (CF-LVADs) is often related to GI angiodysplasia (GIAD). We previously reported data on VEGF inhibition with IV bevacizumab in the treatment of LVAD-associated GIAD bleeding, and now present follow-up data on patients treated with IV bevacizumab and/or low-dose oral pazopanib. METHODS: All consecutive adult patients with LVAD-associated GIB from GIAD treated with bevacizumab or pazopanib, from July 20, 2017 to June 22, 2022, were included in the analysis. Data on hospitalizations, GI endoscopic procedures, and blood transfusions were obtained from first admission for GIB up to a median of 35.7 months following treatment initiation (range 1.3-59.8 months). RESULTS: Eleven patients (91% male, mean 69.5 ± 8.9 years) were included. Eight patients (73%) received IV bevacizumab, two patients (18%) received oral pazopanib, and one patient (9%) received bevacizumab followed by pazopanib therapy. We observed a significantly decreased number of annualized hospitalizations for GIB (median difference - 2.87, p = 0.002), blood transfusions (median difference - 20.9, p = 0.01), and endoscopies (median difference - 6.95, p = 0.007) in patients pre- and post-anti-angiogenic therapy (bevacizumab and/or pazopanib). Similarly, a significant improvement in these clinical outcomes was noted in the bevacizumab group with decreased annualized hospitalizations (median difference - 2.75, p = 0.014), blood transfusions (median difference - 24.5, p = 0.047), and number of endoscopies (median differences -6.88, p = 0.006). CONCLUSION: Anti-angiogenic therapy with IV bevacizumab and/or low-dose oral pazopanib appears to provide benefits in patients with LVAD-associated GIB with reduced hospitalizations, blood transfusions, and need for GI endoscopic procedures.

Preemptive antiviral therapy in lung transplantation from hepatitis C donors results in a rapid and sustained virologic response.

Objective: The study objective was to assess the safety and efficacy of a preemptive direct-acting antiviral therapy in lung transplants from hepatitis C virus donors to uninfected recipients. Methods: This study is a prospective, open-label, nonrandomized, pilot trial. Recipients of hepatitis C virus nucleic acid test positive donor lungs underwent preemptive direct-acting antiviral therapy with glecaprevir 300 mg/pibrentasvir 120 mg for 8 weeks from January 1, 2019, to December 31, 2020. Recipients of nucleic acid test positive lungs were compared with recipients of lungs from nucleic acid test negative donors. Primary end points were Kaplan-Meier survival and sustained virologic response. Secondary outcomes included primary graft dysfunction, rejection, and infection. Results: Fifty-nine lung transplantations were included: 16 nucleic acid test positive and 43 nucleic acid test negative. Twelve nucleic acid test positive recipients (75%) developed hepatitis C virus viremia. Median time to clearance was 7 days. All nucleic acid test positive patients had undetectable hepatitis C virus RNA by week 3, and all alive patients (n = 15) remained negative during follow-up with 100% sustained virologic response at 12 months. One nucleic acid test positive patient died of primary graft dysfunction and multiorgan failure. Three of 43 nucleic acid test negative patients (7%) had hepatitis C virus antibody positive donors. None of them developed hepatitis C virus viremia. One-year survival was 94% for nucleic acid test positive recipients and 91% for nucleic acid test negative recipients. There was no difference in primary graft dysfunction, rejection, or infection. One-year survival for nucleic acid test positive recipients was similar to a historical cohort of the Scientific Registry of Transplant Recipients (89%). Conclusions: Recipients of hepatitis C virus nucleic acid test positive lungs have similar survival as recipients of nucleic acid test negative lungs. Preemptive direct-acting antiviral therapy results in rapid viral clearance and sustained virologic response at 12 months. Preemptive direct-acting antiviral may partially prevent hepatitis C virus transmission.

Expanded extracorporeal membrane oxygenation bridge to heart and lung transplant candidate selection does not impact outcomes compared to traditional candidate selection criteria.

Extracorporeal membrane oxygenation is used as a bridge to transplant (ECMO-BTT) in selected patients. The objective of this study was to determine whether 1-year post-transplant and post-ECMO survival are impacted by traditional compared to expanded selection criteria. We performed a retrospective study of patients >17 years who received ECMO as bridge to transplant (BTT) or bridge to transplant decision for lung or combined heart and lung transplantation at the Mayo Clinic Florida and Rochester. Institutional protocol excludes patients >55 years, maintained on steroids, unable to participate in physical therapy, with body mass index >30 or <18.5 kg/m2, non-pulmonary end-organ dysfunction, or unmanageable infections from ECMO-BTT. For this study, adherence to this protocol was considered traditional whereas exceptions to the protocol were considered expanded selection criteria. A total of 45 patients received ECMO as bridge therapy. Out of those 29 patients (64%) received ECMO as bridge to transplant and 16 patients (36%) as bridge to transplant decision. The traditional criteria cohort consisted of 15 (33%) patients and expanded criteria cohort consisted of 30 (67%) patients. In the traditional cohort, 9 (60%) of 15 patients were successfully transplanted compared to 16 (53%) of 30 patients in the expanded criteria cohort. No difference in being delisted or dying on the waitlist (OR: 0.58, CI: 0.13-2.58), surviving to 1-year post-transplant (OR: 0.53, CI: 0.03-9.71) or 1-year post-ECMO (OR: 0.77, CI: 0.0.23-2.56) was observed between the traditional criteria and expanded criteria cohorts. At our institution, we did not see differences in odds of 1-year post-transplant and post-ECMO survival between those who met traditional criteria compared to those who did not. Multicenter, prospective studies are needed to evaluate the impact of ECMO-BTT selection criteria.

Cardiac Transplantation: Physiology and Natural History of the Transplanted Heart.

Heart transplantation (HT) is one of the prodigious achievements in modern medicine and remains the cornerstone in the treatment of patients with advanced heart failure. Advances in surgical techniques, immunosuppression, organ preservation, infection control, and allograft surveillance have improved short- and long-term outcomes thereby contributing to greater clinical success of HT. However, prolonged allograft and patient survival following HT are still largely restricted by the development of late complications, including allograft rejection, infection, cardiac allograft vasculopathy (CAV), and malignancy. The introduction of mTOR inhibitors early after HT has demonstrated multiple protective effects against CAV progression, renal dysfunction, and tumorigenesis. Therefore, several HT programs increasingly use mTOR inhibitors with partial or complete withdrawal of calcineurin inhibitor (CNI) in stable HT patients to reduce complications risk and improve long-term outcomes. Furthermore, despite a substantial improvement in exercise capacity and health-related quality of life after HT as compared to advanced heart failure patients, most HT recipients remain with a 30% to 50% lower peak oxygen consumption (Vo 2 ) than that of age-matched healthy subjects. Several factors, including alterations in central hemodynamics, HT-related complications and alterations in the musculoskeletal system, and peripheral physiological abnormalities, presumably contribute to the reduced exercise capacity following HT. Cardiac denervation and subsequent loss of sympathetic and parasympathetic regulation are responsible for various physiological alterations in the cardiovascular system, which contributes to restricted exercise tolerance. Restoration of cardiac innervation may improve exercise capacity and quality of life, but the reinnervation process is only partial even several years after HT. Multiple studies have shown that aerobic and strengthening exercise interventions improve exercise capacity by increasing maximal heart rate, chronotropic response, and peak Vo 2 after HT. Novel exercise modalities, such as high-intensity interval training (HIT), have been proven as safe and effective for further improvement in exercise capacity, including among de novo HT recipients. Further developments have recently emerged, including donor heart preservation techniques, noninvasive CAV and rejection surveillance methods, and improvements in immunosuppressive therapies, all aiming at increasing donor availability and improving late survival after HT. © 2023 American Physiological Society. Compr Physiol 13:4719-4765, 2023.

Infections in Patients With Left Ventricular Assist Devices: Current State and Future Perspectives.

Mechanical circulatory support is increasingly being used as bridge-to-transplant and destination therapy in patients with advanced heart failure. Technologic improvements have led to increased patient survival and quality of life, but infection remains one of the leading adverse events following ventricular assist device (VAD) implantation. Infections can be classified as VAD-specific, VAD-related, and non-VAD infections. Risk of VAD-specific infections, such as driveline, pump pocket, and pump infections, remains for the duration of implantation. While adverse events are typically most common early (within 90 days of implantation), device-specific infection (primarily driveline) is a notable exception. No diminishment over time is seen, with event rates of 0.16 events per patient-year in both the early and late periods postimplantation. Management of VAD-specific infections requires aggressive treatment and chronic suppressive antimicrobial therapy is indicated when there is concern for seeding of the device. While surgical intervention/hardware removal is often necessary in prosthesis-related infections, this is not so easily accomplished with VADs. This review outlines the current state of infections in patients supported with VAD therapy and discusses future directions, including possibilities with fully implantable devices and novel approaches to treatment.

Impact of concomitant coronary artery bypass grafting on postoperative outcomes in patients undergoing pericardiectomy: A 33-year experience.

Objective: Concomitant coronary artery bypass grafting (CABG) and pericardiectomy (PC) can be a technically challenging operation. We sought to study the outcomes of patients undergoing concomitant PC and CABG. Methods: Between July 1983 and August 2016, 70 patients (median age, 67 years; 88% males) underwent concomitant PC and CABG (PC + CABG group). Multivariable analysis was used to identify predictors of mortality. Matched patients who underwent isolated PC (PC group) were identified, and postoperative outcomes and long-term survival in the 2 groups were compared. Results: Compared with the PC group, cardiopulmonary bypass time was significantly longer in the PC + CABG group (82 minutes vs 61 minutes; P < .001). In-hospital mortality was 4% in the PC group and 7% in the PC + CABG group (P = .380). Multivariable analysis identified peripheral vascular disease (hazard ratio [HR], 2.67; 95% CI, 1.06-6.76; P = .04) as a predictor of increased morbidity or mortality and a borderline association with New York Heart Association functional classes III and IV (HR, 2.41; 95% CI, 0.99-5.86; P = .05) with increased morbidity and mortality in the PC + CABG group. Kaplan-Meier estimates demonstrated similar late mortality rates in the 2 groups at a 15-year follow-up (P = .700). Conclusions: Concomitant PC and CABG is not associated with increased morbidity or mortality compared with isolated PC. Thus, CABG should not be denied at the time of PC.

Percutaneous Mechanical Circulatory Support as a Bridge to Transplantation in Ebstein Anomaly.

Ebstein anomaly is a rare congenital heart defect occurring in 0.0005% of the population because of mispositioning and malformation of the tricuspid valve. Here, we present the first description and associated imaging of percutaneous mechanical circulatory support in the setting of cardiogenic shock secondary to Ebstein anomaly.

Heart Transplantation from COVID-19-Positive Donors: A Word of Caution.

BACKGROUND: During the COVID-19 pandemic, efforts to maintain solid-organ transplantation have continued, including the use of SARS-CoV-2-positive heart donors. METHODS: We present our institution's initial experience with SARS-CoV-2-positive heart donors. All donors met our institution's Transplant Center criteria, including a negative bronchoalveolar lavage polymerase chain reaction result. All but 1 patient received postexposure prophylaxis with anti-spike monoclonal antibody therapy, remdesivir, or both. RESULTS: A total of 6 patients received a heart transplant from a SARS-CoV-2-positive donor. One heart transplant was complicated by catastrophic secondary graft dysfunction requiring venoarterial extracorporeal membrane oxygenation and retransplant. The remaining 5 patients did well postoperatively and were discharged from the hospital. None of the patients had evidence of COVID-19 infection after surgery. CONCLUSION: Heart transplants from SARS-CoV-2 polymerase chain reaction-positive donors are feasible and safe with adequate screening and postexposure prophylaxis.

Interventricular-Septal Output While Supported on Left Ventricular Assist Device Therapy.

The effects of left ventricular unloading on septal function in patients with left ventricular assist devices (LVADs) have not been well characterized in vivo. The purpose of this study was to evaluate the relationship between markers of septal function with echocardiography in relationship to RV dysfunction and late RV failure after LVAD implantation. A retrospective study was conducted of patients supported on centrifugal-flow LVADs implanted over a 10-year period. Echocardiographic data were collected pre-operatively and up to 2 years after implantation. Interventricular septum (IVS) measurements were taken at end-systole and end-diastole. Interventricular-septal output (ISO) was calculated using the formula: (IVSs-IVSd)×heart rate. A total of 110 patients were included. An immediate and sustained reduction in both lateral annulus systolic velocity (RVS') and TAPSE were observed after implant ( p < 0.0001). However, ISO gradually decreased over time ( p < 0.0001). While ISO was not predictive of late RV failure, a decrease in ISO by 25% or greater from pre-implant to hospital discharge was associated with late RV failure (OR 4.8; 95% CI, 1.4-16.5; p = 0.012) even after adjusting for relevant clinical variables ( p ≤ 0.01 for each model). RV function is known to be influenced by mechanical ventricular interdependence and we demonstrate that measurement of ISO may be a useful marker in assessing RV dysfunction and predicting RV failure in patients following LVAD implantation.

Pulsatile Pressure Delivery of Continuous-Flow Left Ventricular Assist Devices Is Markedly Reduced Relative to Heart Failure Patients.

Although continuous-flow left ventricular assist devices (CF-LVADs) provide an augmentation in systemic perfusion, there is a scarcity of in vivo data regarding systemic pulsatility on support. Patients supported on CF-LVAD therapy (n = 71) who underwent combined left/right catheterization ramp study were included. Aortic pulsatility was defined by the pulsatile power index (PPI), which was also calculated in a cohort of high-output heart failure (HOHF, n = 66) and standard HF cohort (n = 44). PPI was drastically lower in CF-LVAD-supported patients with median PPI of 0.006 (interquartile range [IQR], 0.002-0.012) compared with PPI in the HF population at 0.09 (IQR, 0.06-0.17) or HOHF population at 0.25 (IQR, 0.13-0.37; p < 0.0001 among groups). With speed augmentation during ramp, PPI values fell quickly in patients with higher PPI at baseline. PPI correlated poorly with left ventricular ejection fraction (LVEF) in all groups. In CF-LVAD patients, there was a stronger correlation with LV dP/dt (r = 0.41; p = 0.001) than LVEF (r = 0.21; p = 0.08; pint < 0.001). CF-LVAD support is associated with a dramatic reduction in arterial pulsatility as measured by PPI relative to HOHF and HF cohorts and decreases with speed. Further work is needed to determine the applicability to the next generation of device therapy.

Early national trends of lung allograft use during donation after circulatory death heart procurement in the United States.

Objective: Innovative technology such as normothermic regional perfusion and the Organ Care System has expanded donation after circulatory death heart transplantation. We wanted to investigate the impact of donation after circulatory death heart procurement in concurrent lung donation and implantation at a national level. Methods: We reviewed the United Network for Organ Sharing database for heart donation between December 2019 and March 2022. Donation after circulatory death donors were separated from donation after brain death donors and further categorized based on concomitant organ procurement of lung and heart, or heart only. Results: A total of 8802 heart procurements consisted of 332 donation after circulatory death donors and 8470 donation after brain death donors. Concomitant lung procurement was lower among donation after circulatory death donors (19.3%) than in donation after brain death donors (38.0%, P < .001). The transplant rate of lungs in the setting of concomitant procurement is 13.6% in donation after circulatory death, whereas it is 38% in donation after brain death (P < .001). Of the 121 lungs from 64 donation after circulatory death donors, 22 lungs were retrieved but discarded (32.2%). Normothermic regional perfusion was performed in 37.3% of donation after circulatory death donors, and there was no difference in lung use between normothermic regional perfusion versus direct procurement and perfusion (20.2% and 18.8%). There was also no difference in 1-year survival between normothermic regional perfusion and direct procurement and perfusion. Conclusions: Although national use of donation after circulatory death hearts has increased, donation after circulatory death lungs has remained at a steady state. The implantation of lungs after concurrent procurement with the heart remains low, whereas transplantation of donation after circulatory death hearts is greater than 90%. The use of normothermic regional perfusion lungs has been controversial, and we report comparable 1-year outcomes to standard donation after circulatory death lungs. Further studies are warranted to investigate the underlying mechanisms of normothermic regional perfusion on lung function.

Lung transplantation long-term survival is worse in patients who have undergone previous cardiac surgery.

OBJECTIVES: Approximately 10% of lung transplant recipients have had previous cardiothoracic surgery. We sought to determine if previous surgery affects outcomes after lung transplant at a national level. METHODS: The United Network for Organ Sharing database was analysed from 2005 to 2019 to include adult patients who underwent lung transplant who had previous cardiac surgery and previous thoracic surgery. T-test and chi-squared analysis were used to compare perioperative outcomes. Long-term survival comparison was performed using the Kaplan-Meier method in an unadjusted and propensity-matched analysis. RESULTS: Out of 24 784 lung transplants, 691 (2.7%) had previous cardiac surgery and 1321 (6.5%) had previous thoracic surgery. Operative mortality was worse in previous cardiac surgery [42 (6.1%)] versus no previous cardiac surgery [740 (3.1%), P < 0.001] and in previous thoracic surgery [65 (4.9%)] versus no previous thoracic surgery [717 (3.1%), P < 0.001]. The previous thoracic surgery group had more primary graft failure and treated rejection during the first-year post-transplant. There was no difference in stroke, dialysis, intubation and extracorporeal membrane oxygenation at 72 h. Long-term survival was significantly worse for lung transplant patients who had undergone previous cardiac surgery (median 3.8 vs 6.3 years, P < 0.001) due to an increase in cardiovascular deaths (P = 0.008) and malignancy (P = 0.043). However, there was no difference in previous thoracic surgery (median 6.6 vs 6.1 years, P = 0.337). CONCLUSIONS: Previous cardiac surgery prior to lung transplant results in worse survival related to cardiovascular death and malignancies. Previous thoracic surgery worsens perioperative outcomes but does not affect long-term survival.