Transplantation Outcomes with Donor Hearts after Circulatory Death.

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

Acute Kidney Injury in Patients Undergoing Surgery for Type A Acute Aortic Dissection.

BACKGROUND: Acute kidney injury (AKI) after repair of type A acute aortic dissection (TAAAD) has been shown to affect both short- and long-term outcomes. This study aimed to validate the impact of postoperative AKI on in-hospital and long-term outcomes in a large population of dissection patients presenting to multinational aortic centers. Additionally, we assessed risk factors for AKI including surgical details. METHODS: Patients undergoing surgical repair for TAAAD enrolled in the International Registry of Acute Aortic Dissection database were evaluated to determine the incidence and risk factors for the development of AKI. RESULTS: A total of 3307 patients were identified. There were 761 (23%) patients with postoperative AKI (AKI group) vs 2546 patients without (77%, non-AKI group). The AKI group had a higher rate of in-hospital mortality (n = 193, 25.4% vs n = 122, 4.8% in the non-AKI group, P < .001). Additional postoperative complications were also more common in the AKI group including postoperative cerebrovascular accident, reexploration for bleeding, and prolonged ventilation. Independent baseline characteristics associated with AKI included a history of hypertension, diabetes, chronic kidney disease, evidence of malperfusion on presentation, distal extent of dissection to abdominal aorta, and longer cardiopulmonary bypass time. Kaplan-Meier survival curves revealed decreased 5-year survival among the AKI group (P < .001). CONCLUSIONS: AKI occurs commonly after TAAAD repair and is associated with a significantly increased risk of operative and long-term mortality. In this large study using the International Registry of Acute Aortic Dissection database, several factors were elucidated that may affect risk of AKI.

Initial hospital length of stay and long-term survival of patients successfully resuscitated using extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest.

AIMS: The long-term outcomes of patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) for refractory ventricular tachycardia/ventricular fibrillation (VT/VF) out-of-hospital cardiac arrest (OHCA) remain poorly defined. The purpose of this study was to describe the hospital length of stay and long-term survival of patients who were successfully rescued with ECPR after refractory VT/VF OHCA. METHODS AND RESULTS: In this retrospective cohort study, the length of index admission and long-term survival of patients treated with ECPR after OHCA at a single centre were evaluated. In a sensitivity analysis, survival of patients managed with left ventricular assist device (LVAD) implantation or heart transplantation during the same period was also evaluated. Between 1 January 2016 and 12 January 2020, 193 patients were transferred for ECPR considerations and 160 underwent peripheral veno-arterial extracorporeal membrane oxygenation cannulation. Of these, 54 (33.7%) survived the index admission. These survivors required a median 16 days of intensive care and 24 days total hospital stay. The median follow-up time of the survivors was 1216 (683, 1461) days. Of all, 79.6 and 72.2% were alive at 1 and 4 years, respectively. Most deaths within the first year occurred among the patients requiring discharge to a long-term acute care facility. Overall survival rates at 4 years were similar in the ECPR and LVAD cohorts (P = 0.30) but were significantly higher for transplant recipients (P < 0.001). CONCLUSION: This data suggest that the lengthy index hospitalization required to manage OHCA patients with ECPR is rewarded by excellent long-term clinical outcomes in an expert ECPR programme.

Rapidly Progressive and Catastrophic Calciphylaxis After Mechanical Valve Replacement: An Anticoagulation Dilemma.

Warfarin is the only approved anticoagulant after mechanical valve replacement, but it is a well described risk factor for calciphylaxis among patients with end-stage kidney disease. Our patient with end-stage kidney disease rapidly developed calciphylaxis after dual mechanical valve replacement in association with warfarin initiation, posing significant challenges in clinical management and a fatal outcome. (Level of Difficulty: Intermediate.).

Hemodynamic Characteristics and Outcomes of Pulmonary Hypertension in Patients Undergoing Tricuspid Valve Repair or Replacement.

BACKGROUND: The impact of pulmonary hypertension (PH) on outcomes after surgical tricuspid valve replacement (TVR) and repair (TVr) is unclear. We sought to characterize PH in patients undergoing TVR/TVr, based on invasive hemodynamics and evaluate the effect of PH on mortality. METHODS: We identified 86 consecutive patients who underwent TVR/TVr with invasive hemodynamic measurements within 3 months before surgery. We used Kaplan-Meier survival and restricted mean survival time (RMST) analyses to quantify the effects of PH on survival. RESULTS: The mean age was 63 ± 13 years, 59% were female, 45% had TVR, 55% had TVr, 39.5% had isolated TVR/TVr, and 60.5% had TVR/TVr concomitant with other cardiac surgeries). Eighty-six percent of these patients had PH with a mean pulmonary artery pressure of 30 ± 10 mm Hg, pulmonary vascular resistance (PVR) of 2.5 (interquartile range: 1.5-3.9) Wood units (WU), pulmonary arterial compliance of 2.3 (1.6-3.6) mL/mm Hg, and pulmonary arterial elastance of 0.8 (0.6-1.2) mm Hg/mL. Cardiac output was mildly reduced at 4.0 ± 1.4 L/min, with elevated right-atrial pressure (14 ± 12 mm Hg) and pulmonary capillary wedge pressure (19 ± 7 mm Hg). Over a median follow-up of 6.3 years, 22% of patients died. Patients with PVR ≥ 2.5 WU had lower RMST over 5 years compared with patients with PVR < 2.5 WU. CONCLUSION: PH is common in patients undergoing TVR/TVr, with combined pre- and postcapillary being the most common type. PVR ≥ 2.5 WU is associated with lower survival at 5-year follow-up.

CONTEXTE: On connaît mal les répercussions de l'hypertension pulmonaire (HP) chez les patients qui ont subi une intervention chirurgicale de remplacement de la valve tricuspide (RVT) ou de réparation de la valve tricuspide (rVT). Nous avons tenté de caractériser l'HP chez les patients ayant subi un RVT ou une rVT en fonction des paramètres de surveillance hémodynamique effractive et d'évaluer l'effet de l'HP sur la mortalité. MÉTHODOLOGIE: Nous avons relevé 86 patients consécutifs ayant subi un RVT ou une rVT qui avaient fait l'objet de mesures hémodynamiques effractives dans les trois mois précédant l'intervention chirurgicale. Pour quantifier les effets de l'HP sur la survie, nous avons analysé la survie au moyen de la méthode de Kaplan-Meier et de la survie moyenne restreinte. RÉSULTATS: Les patients avaient en moyenne 63 ± 13 ans; 59 % d'entre eux étaient des femmes; 45 % avaient subi un RVT et 55 %, une rVT; 39,5 % avaient subi seulement un RVT ou une rVT lors de l'intervention chirurgicale; 60,5 % avaient subi un RVT ou une rVT en même temps qu'une autre intervention cardiaque. Quatre-vingt-six pour cent de ces patients présentaient une HP avec une pression artérielle pulmonaire moyenne de 30 ± 10 mmHg, une résistance vasculaire pulmonaire (RVP) de 2,5 (intervalle interquartile : 1,5 à 3,9) unités de Wood (UW), une compliance artérielle pulmonaire de 2,3 (1,6 à 3,6) ml/mmHg et une élastance artérielle pulmonaire de 0,8 (0,6 à 1,2) mmHg/ml. On a observé une légère baisse du débit cardiaque à 4,0 ± 1,4 L/min, ainsi qu'une augmentation de la pression auriculaire droite (14 ± 12 mmHg) et de la pression artérielle pulmonaire d'occlusion (19 ± 7 mmHg). Sur une période médiane de suivi de 6,3 ans, 22 % des patients sont décédés. Le taux de survie moyenne restreinte à 5 ans était plus faible chez les patients présentant une RVP ≥ 2,5 UW que chez les patients présentant une RVP < 2,5 UW. CONCLUSION: L'HP est fréquente chez les patients subissant un RVT ou une rVT, le type le plus courant étant l'HP mixte (pré-capillaire et post-capillaire). Une RVP ≥ 2,5 UW est associée à un taux de survie à 5 ans plus faible.

Separate Effect of Perioperative Recombinant Human Factor VIIa Administration and Packed Red Blood Cell Transfusions on Midterm Survival in Lung Transplantation Recipients.

OBJECTIVE: The purpose of this study was to determine the relationship between blood product transfusion, with or without recombinant human activated factor VIIa, and survival after lung transplantation. DESIGN: Retrospective analysis of a single center with follow-up out to 6 years post-transplantation. SETTING: Single-center academic lung transplantation program. PARTICIPANTS: The study comprised 265 adult patients who underwent single or bilateral sequential lung transplantation from March 2011 to June 2017. INTERVENTIONS: Overall survival using Kaplan-Meier curves was compared among the following 3 cohorts: those not transfused with blood products, those transfused with blood products, and those given blood products and recombinant human activated factor VIIa. Cox proportional hazards regression was used to estimate hazard ratios (HRs), confidence intervals (CIs), and p values. MEASUREMENTS AND MAIN RESULTS: Seventy-eight patients received no packed red blood cell transfusions, 149 received packed red blood cell transfusions, and 38 received both packed red blood cell transfusions and recombinant human activated factor VII. Packed red blood cell transfusion was associated with an increased risk of mortality that did not reach statistical significance (HR 2.168, CI 0.978-4.805; p = 0.057). Additional packed red blood cells beyond 15 U were associated with worsened survival (HR 1.363, CI 1.137-1.633; p = 0.001), but recombinant human activated factor VIIa did not increase the risk of mortality. CONCLUSION: Blood product transfusion during and after lung transplantation is associated with decreased survival, especially with large-volume transfusions. Survival is not worse with recombinant human activated factor VIIa administration, but additional studies are needed to determine whether recombinant human activated factor VIIa administration reduces the need for blood product transfusions.

Multimodal functional and still imaging of a transplanted human heart reanimated using Visible Heart® methodologies.

BACKGROUND: Our research team obtained a human heart with the right lung attached from a recent transplantation patient via a research collaboration with LifeSource, a local organ procurement organization. The heart and lungs were not viable for transplant given the patient's medical history and were subsequently offered to the University of Minnesota for research purposes. METHODS: Using Visible Heart® methodologies, we reanimated the specimen en bloc and collected multimodal direct visualization from inside the cardiac chambers and great vessels of the functioning heart. RESULTS: Video footage, using videoscopic and fluoroscopic imaging, was captured and is presented in this report as supporting material. Multiple still images highlight the surgical suture sites of the transplantation procedures. CONCLUSIONS: This multimodal imaging offers unique educational value for medical students, clinicians, and medical device designers for improving transplantation techniques and patient outcomes.

Need for tracheostomy after lung transplant predicts decreased mid- and long-term survival.

BACKGROUND: Tracheostomy is an important adjunct for lung transplant patients requiring prolonged ventilation. We explored the effects of post-transplant tracheostomy on survival and bronchiolitis obliterans syndrome after lung transplant. METHODS: A retrospective, single center analysis was performed on all lung transplant recipients during the Lung Allocation Score (LAS) era. Risk factors for post-transplant tracheostomy or death within 30 days were assessed. Kaplan-Meier estimates and Cox proportional hazards models were used to examine the association between tracheostomy within 30 days after transplant and survival at 1 and 3 years. A total of 403 patients underwent single or bilateral lung transplant between May 2005 and February 2016 with complete data for 352 cases, and 35 patients (9.9%) underwent tracheostomy or died (N = 10, 2.8%) within 30 days. RESULTS: In adjusted analyses, primary graft dysfunction grade 3 (PGD3) was associated with a composite end point of tracheostomy or death within 30 days (HR 3.11 (1.69, 5.71), P-value < .001). Tracheostomy within 30 days was associated with decreased survival at 1(HR 4.25 [1.75, 10.35] P-value = .001) and 3 years (HR 2.74 [1.30, 5.76], P-value = .008), as well as decreased bronchiolitis obliterans (BOS)-free survival at 1 (HR 1.87 [1.02, 3.41] P-value = .042) and 3 years (HR 2.15 [1.33, 3.5], P-value = .002). CONCLUSION: Post-transplant tracheostomy is a marker for advanced lung allograft dysfunction with significant reduction in long-term overall and BOS-free survival.

Cerebral Oxygenation of Premature Lambs Supported by an Artificial Placenta.

An artificial placenta (AP) using venovenous extracorporeal life support (VV-ECLS) could represent a paradigm shift in the treatment of extremely premature infants. However, AP support could potentially alter cerebral oxygen delivery. We assessed cerebral perfusion in fetal lambs on AP support using near-infrared spectroscopy (NIRS) and carotid arterial flow (CAF). Fourteen premature lambs at estimated gestational age (EGA) 130 days (term = 145) underwent cannulation of the right jugular vein and umbilical vein with initiation of VV-ECLS. An ultrasonic flow probe was placed around the right carotid artery (CA), and a NIRS sensor was placed on the scalp. Lambs were not ventilated. CAF, percentage of regional oxygen saturation (rSO2) as measured by NIRS, hemodynamic data, and blood gases were collected at baseline (native placental support) and regularly during AP support. Fetal lambs were maintained on AP support for a mean of 55 ± 27 hours. Baseline rSO2 on native placental support was 40% ± 3%, compared with a mean rSO2 during AP support of 50% ± 11% (p = 0.027). Baseline CAF was 27.4 ± 5.4 ml/kg/min compared with an average CAF of 23.7 ± 7.7 ml/kg/min during AP support. Cerebral fractional tissue oxygen extraction (FTOE) correlated negatively with CAF (r = -0.382; p < 0.001) and mean arterial pressure (r = -0.425; p < 0.001). FTOE weakly correlated with systemic O2 saturation (r = 0.091; p = 0.017). Cerebral oxygenation and blood flow in premature lambs are maintained during support with an AP. Cerebral O2 extraction is inversely related to carotid flow and is weakly correlated with systemic O2 saturation.

Use of a low-resistance compliant thoracic artificial lung in the pulmonary artery to pulmonary artery configuration.

BACKGROUND: Thoracic artificial lungs have been proposed as a bridge to transplant in patients with end-stage lung disease. Systemic embolic complications can occur after thoracic artificial lung attachment in the pulmonary artery to left atrium configuration. Therefore, we evaluated the function of a compliant thoracic artificial lung attached via the proximal pulmonary artery to distal main pulmonary artery configuration. METHODS: The compliant thoracic artificial lung was attached to 5 sheep (63 ± 0.9 kg) in the proximal pulmonary artery to distal main pulmonary artery configuration. Device function and animal hemodynamics were assessed at baseline and with approximately 60%, 75%, and 90% of cardiac output diverted to the compliant thoracic artificial lung. At each condition, dobutamine (0 and 5 µg·kg(-1)·min(-1)) was used to simulate rest and exercise conditions. RESULTS: At rest, cardiac output decreased from 6.20 ± 0.53 L/min at baseline to 5.40 ± 0.43, 4.66 ± 0.31, and 4.05 ± 0.27 L/min with 60%, 75%, and 90% of cardiac output to the compliant thoracic artificial lung, respectively (P < .01 for each flow diversion vs baseline). During exercise, cardiac output decreased from 7.85 ± 0.70 L/min at baseline to 7.46 ± 0.55, 6.93 ± 0.51, and 5.96 ± 0.44 L/min (P = .82, P = .19, and P < .01 with respect to baseline) with 60%, 75%, and 90% of cardiac output to the compliant thoracic artificial lung, respectively. The artificial lung resistance averaged 0.46 ± 0.02 and did not vary significantly with blood flow rate. CONCLUSIONS: Use of a compliant thoracic artificial lung may be feasible in the proximal pulmonary artery to distal main pulmonary artery setting if its blood flow is held at less than 75% of cardiac output. To ensure a decrease in cardiac output of less than 10%, a blood flow rate less than 60% of cardiac output is advised.

Advances in neonatal extracorporeal support: the role of extracorporeal membrane oxygenation and the artificial placenta.

This review addresses the history and evolution of neonatal extracorporeal membrane oxygenation (ECMO), with a discussion of the indications, contraindications, modalities, outcomes, and impact of ECMO. Controversies surrounding novel uses of ECMO in neonates, namely ECMO for premature infants and ex utero intrapartum therapy with transition to ECMO, are discussed. The development of an extracorporeal artificial placenta for support of premature infants is presented, including the rationale, research, and challenges. ECMO has had a dramatic effect on the care of critically ill neonates over the past 4 decades, and there is great potential to expand these benefits in the future.

Comparison study of the solution phase versus solid phase place exchange reactions in the controlled functionalization of gold nanoparticles.

Gold nanoparticles offer tremendous potential in the areas of nanoelectronics, bio- and chemosensors, and catalysis. However, before these applications are realized, the surface functionality of nanoparticles must be better controlled. Our lab has recently reported a novel synthetic approach for making monofunctionalized nanoparticles through a solid phase place exchange reaction. Monofunctionalized gold nanoparticles may also be prepared through a solution phase place exchange reaction. In this study, we compared the efficiency of these two separate approaches toward controlled functionalization of gold nanoparticles by (1)H NMR, Fourier transform infrared (FT-IR), and transmission electron microscopy (TEM) analysis. We found that the solid phase place exchange approach is much more efficient at producing monofunctionalized gold nanoparticles. (1)H NMR data were used to give a semiquantitative count of substituted bifunctional ligands, and FT-IR spectra supported these findings. Furthermore, we used a diamine coupling reaction of nanoparticles to show the presence of single or multiple functional groups on the nanoparticle surface by TEM analysis.

Controlled functionalization of gold nanoparticles through a solid phase synthesis approach.

A novel solid phase synthetic strategy was developed in this work for controlled functionalization of gold nanoparticles.