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.).

Rationale and Design of the Randomized Controlled Trial of New Oral Anticoagulants Versus Warfarin for Post Cardiac Surgery Atrial Fibrillation: The NEW-AF Trial.

OBJECTIVE: This manuscript describes the rationale and design of a randomized, controlled trial comparing outcomes with Warfarin vs Novel Oral Anticoagulant (NOAC) therapy in patients with new onset atrial fibrillation after cardiac surgery. BACKGROUND: New onset atrial fibrillation commonly occurs after cardiac surgery and is associated with increased rates of stroke and mortality. in nonsurgical patients with atrial fibrillation, NOACs have been shown to confer equivalent benefits for stroke prevention with less bleeding risk and less tedious monitoring requirements compared with Warfarin. However, NOAC use has yet to be adopted widely in cardiac surgery patients. METHODS: The NEW-AF study has been designed as a pragmatic, prospective, randomized controlled trial that will compare financial, convenience and safety outcomes for patients with new onset atrial fibrillation after cardiac surgery that are treated with NOACs versus Warfarin. RESULTS: Study results may contribute to optimizing the options for stroke prophylaxis in cardiac surgery patients and catalyze more widespread application of NOAC therapy in this patient population. CONCLUSIONS: The study is ongoing and actively enrolling at the time of the publication. The trial is registered with clinicaltrials.gov under registration number NCT03702582.

Progress Toward Cardiac Xenotransplantation.

Consistent survival of life-supporting pig heart xenograft recipients beyond 90 days was recently reported using genetically modified pigs and a clinically applicable drug treatment regimen. If this remarkable achievement proves reproducible, published benchmarks for clinical translation of cardiac xenografts appear to be within reach. Key mechanistic insights are summarized here that informed recent pig design and therapeutic choices, which together appear likely to enable early clinical translation.

Extracorporeal cardiopulmonary resuscitation (ECPR) survival: A quaternary center analysis.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a rescue strategy for nonresponders to conventional CPR (CCPR) in cardiac arrest. Definitive guidelines for ECPR deployment do not exist. Prior studies suggest that arrest rhythm and cardiac origin of arrest may be variables used to assess candidacy for ECPR. AIM: To describe a single-center experience with ECPR and to assess associations between survival and physician-adjudicated origin of arrest and arrest rhythm. METHODS: A retrospective review of all patients who underwent ECPR at a quaternary care center over a 7-year period was performed. Demographic and clinical characteristics were extracted from the medical record and used to adjudicate the origin of cardiac arrest, etiology, rhythm, survival, and outcomes. Univariate analysis was performed to determine the association of patient and arrest characteristics with survival. RESULTS: Between 2010 and 2017, 47 cardiac arrest patients were initiated on extracorporeal membrane oxygenation (ECMO) at the time of active CPR. ECPR patient survival to hospital discharge was 25.5% (n = 12). Twenty-six patients died on ECMO (55.3%) while nine patients (19.1%) survived decannulation but died before discharge. Neither physician-adjudicated arrest rhythm nor underlying origin were significantly associated with survival to discharge, either alone or in combination. Younger age was significantly associated with survival. Nearly all survivors experienced myocardial recovery and left the hospital with a good neurological status. CONCLUSIONS: Arrest rhythm and etiology may be insufficient predictors of survival in ECPR utilization. Further multiinstitutional studies are needed to determine evidenced-based criteria for ECPR deployment.

Pig-to-human heart transplantation: Who goes first?

Cardiac xenotransplantation has recently taken an important step towards clinical reality. In anticipation of the "first-in-human" heart xenotransplantation trial, we propose a set of patient characteristics that define potential candidates. Our premise is that, to be ethically justified, the risks posed by current state-of-the-art options must outweigh the anticipated risks of a pioneering xenotransplant procedure. Suitable candidates include patients who are at high immunologic risk because of sensitization to alloantigens, including those who have exhibited early onset or accelerated cardiac allograft vasculopathy. In addition, patients should be considered (1) for whom mechanical circulatory support would be prohibitively risky due to a hypercoagulable state, a contraindication to anticoagulation, or restrictive physiology; (2) with severe biventricular dysfunction predicting unsuccessful univentricular left heart support; and (3) adults with complex congenital heart disease. In conclusion, because the published preclinical benchmark for clinical translation of heart xenotransplantation appears within reach, carefully and deliberately defining appropriate trial participants is timely as the basis for ethical clinical trial design.

Veno-venous Extracorporeal Membrane Oxygenation for Respiratory Failure in COVID-19 Patients: Early Experience From a Major Academic Medical Center in North America.

AND BACKGROUND DATA: VV ECMO can be utilized as an advanced therapy in select patients with COVID-19 respiratory failure refractory to traditional critical care management and optimal mechanical ventilation. Anticipating a need for such therapies during the pandemic, our center created a targeted protocol for ECMO therapy in COVID-19 patients that allows us to provide this life-saving therapy to our sickest patients without overburdening already stretched resources or excessively exposing healthcare staff to infection risk. METHODS: As a major regional referral program, we used the framework of our well-established ECMO service-line to outline specific team structures, modified patient eligibility criteria, cannulation strategies, and management protocols for the COVID-19 ECMO program. RESULTS: During the first month of the COVID-19 outbreak in Massachusetts, 6 patients were placed on VV ECMO for refractory hypoxemic respiratory failure. The median (interquartile range) age was 47 years (43-53) with most patients being male (83%) and obese (67%). All cannulations were performed at the bedside in the intensive care unit in patients who had undergone a trial of rescue therapies for acute respiratory distress syndrome including lung protective ventilation, paralysis, prone positioning, and inhaled nitric oxide. At the time of this report, 83% (5/6) of the patients are still alive with 1 death on ECMO, attributed to hemorrhagic stroke. 67% of patients (4/6) have been successfully decannulated, including 2 that have been successfully extubated and one who was discharged from the hospital. The median duration of VV ECMO therapy for patients who have been decannulated is 12 days (4-18 days). CONCLUSIONS: This is 1 the first case series describing VV ECMO outcomes in COVID-19 patients. Our initial data suggest that VV ECMO can be successfully utilized in appropriately selected COVID-19 patients with advanced respiratory failure.

Electroencephalogram Burst-suppression during Cardiopulmonary Bypass in Elderly Patients Mediates Postoperative Delirium.

BACKGROUND: Intraoperative burst-suppression is associated with postoperative delirium. Whether this association is causal remains unclear. Therefore, the authors investigated whether burst-suppression during cardiopulmonary bypass (CPB) mediates the effects of known delirium risk factors on postoperative delirium. METHODS: This was a retrospective cohort observational substudy of the Minimizing ICU [intensive care unit] Neurological Dysfunction with Dexmedetomidine-induced Sleep (MINDDS) trial. The authors analyzed data from patients more than 60 yr old undergoing cardiac surgery (n = 159). Univariate and multivariable regression analyses were performed to assess for associations and enable causal inference. Delirium risk factors were evaluated using the abbreviated Montreal Cognitive Assessment and Patient-Reported Outcomes Measurement Information System questionnaires for applied cognition, physical function, global health, sleep, and pain. The authors also analyzed electroencephalogram data (n = 141). RESULTS: The incidence of delirium in patients with CPB burst-suppression was 25% (15 of 60) compared with 6% (5 of 81) in patients without CPB burst-suppression. In univariate analyses, age (odds ratio, 1.08 [95% CI, 1.03 to 1.14]; P = 0.002), lowest CPB temperature (odds ratio, 0.79 [0.66 to 0.94]; P = 0.010), alpha power (odds ratio, 0.65 [0.54 to 0.80]; P < 0.001), and physical function (odds ratio, 0.95 [0.91 to 0.98]; P = 0.007) were associated with CPB burst-suppression. In separate univariate analyses, age (odds ratio, 1.09 [1.02 to 1.16]; P = 0.009), abbreviated Montreal Cognitive Assessment (odds ratio, 0.80 [0.66 to 0.97]; P = 0.024), alpha power (odds ratio, 0.75 [0.59 to 0.96]; P = 0.025), and CPB burst-suppression (odds ratio, 3.79 [1.5 to 9.6]; P = 0.005) were associated with delirium. However, only physical function (odds ratio, 0.96 [0.91 to 0.99]; P = 0.044), lowest CPB temperature (odds ratio, 0.73 [0.58 to 0.88]; P = 0.003), and electroencephalogram alpha power (odds ratio, 0.61 [0.47 to 0.76]; P < 0.001) were retained as predictors in the burst-suppression multivariable model. Burst-suppression (odds ratio, 4.1 [1.5 to 13.7]; P = 0.012) and age (odds ratio, 1.07 [0.99 to 1.15]; P = 0.090) were retained as predictors in the delirium multivariable model. Delirium was associated with decreased electroencephalogram power from 6.8 to 24.4 Hertz. CONCLUSIONS: The inference from the present study is that CPB burst-suppression mediates the effects of physical function, lowest CPB temperature, and electroencephalogram alpha power on delirium.

Predictors of Neurologic Recovery in Patients Who Undergo Extracorporeal Membrane Oxygenation for Refractory Cardiac Arrest.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) as a rescue strategy during cardiopulmonary resuscitation (ECPR) is increasingly being used for nonresponders to conventional cardiopulmonary resuscitation. To identify patients most likely to benefit from ECPR, the authors investigated predictors of hospital discharge with good neurologic function. DESIGN: Retrospective cohort analysis. SETTING: Single institution academic medical center. PARTICIPANTS: Patients who underwent ECPR. INTERVENTIONS: Venoarterial ECMO initiation for witnessed refractory cardiac arrest from 2009-2019. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics and post-ECMO outcomes were compared between patients who had good versus poor neurologic function at discharge. Good neurologic function was defined as a cerebral performance category 1 to 2, whereas poor neurologic function was defined as a cerebral performance category 3 to 5. Of 54 patients, 13 (24%) were discharged with good neurologic function and 41 (76%) had poor neurologic function (n = 38 in-hospital deaths; n = 3 discharged with severe disability.) Survivors with good neurologic function were younger (41 v 61 y; p = 0.03), more likely to arrest because of pulmonary embolism (46% v 10%; p = 0.01), and more likely to receive concurrent Impella (Abiomed, Danvers, MA) placement while on ECMO (38% v 12%; p = 0.03.) Young age was the most important predictor of good neurologic function (odds ratio 0.92 [0.87-0.97]; p = 0.004), with a threshold for improved survival around 60 years. For all patients, survival to discharge was 30%; however, among survivors with good neurologic function, 5-year survival was 100%. CONCLUSIONS: ECPR is associated with high rates of neurologic morbidity and mortality. However, in select patients, it may be an acceptable option with favorable long-term survival. Additional studies are indicated to further define the appropriate selection criteria for ECPR implementation.

Increasing donor sequence number is not associated with inferior outcomes in lung transplantation.

BACKGROUND: Donor sequence number (DSN) represents the number of recipients to whom an organ has been offered. The impact of seeing numerous prior refusals may potentially influence the decision to accept an organ. We sought to determine if DSN was associated with inferior posttransplant outcomes. METHODS: Using the United Network for Organ Sharing database, a retrospective analysis was performed on 22 361 patients who received a lung transplant between 2005 and 2017. Patients were grouped into low DSN (1-24, n = 16 860) and high DSN (>24, n = 5501) categories. Baseline characteristics and posttransplant outcomes were analyzed. An institutional subgroup was also analyzed to compare rates of primary graft dysfunction (PGD) posttransplant. RESULTS: The DSN ranged from 1 to 1735 (median, 7; interquartile range, 2-24). A total of 18 507 recipients received an organ with at least one prior refusal. Recipients of donors with a higher DSN were older (58 vs 55 years; P < .01) but had lower lung allocation scores (43.5 vs 47.5; P < .01). On adjusted analysis, high DSN was not associated with increased mortality (hazard ratio, 0.99; 95% confidence interval, 0.94-1.04; P = .77). There was no difference in the incidence of graft failure (P = .37) or retransplantation (P = .24). Recipient subgroups who received donors with an increasing DSN >50 and >75 also demonstrated no difference in mortality when compared with a low DSN (P = .86 and P = .97). There was no difference in PGD for patients with a low vs a high DSN at any time posttransplant. CONCLUSIONS: DSN is not associated with increased mortality in patients undergoing lung transplantation and should not negatively influence the decision to accept a lung for transplant.

The effect of donor age on posttransplant mortality in a cohort of adult cardiac transplant recipients aged 18-45.

Hearts from older donors are increasingly utilized for transplantation due to unmet demand. Conflicting evidence exists regarding the prognosis of recipients of advanced age donor hearts, especially in young recipients. A retrospective analysis was performed on 11 433 patients aged 18 to 45 who received a cardiac transplant from 2000 to 2017. Overall, 10 279 patients received hearts from donors less than 45 and 1145 from donors greater than 45. Recipients of older donors were older (37 vs. 34 years, P < .01) and had higher rates of inotropic dependence (48% vs. 42%, P < .01). However, groups were similar in terms of comorbidities and dependence on mechanical circulatory support. Median survival for recipients of older donors was reduced by 2.6 years (12.6 vs. 15.2, P < .01). Multivariable analysis demonstrated donor age greater than 45 to be a predictor of mortality (HR 1.18 [1.05-1.33], P = .01). However, when restricting the analysis to patients who received a donor with a negative preprocurement angiogram, donor age only had a borderline association with mortality (HR 1.20 [0.98-1.46], P = .06). Older donor hearts in young recipients are associated with decreased long-term survival, however this risk is reduced in donors without atherosclerosis. The long-term hazard of this practice should be carefully weighed against the risk of waitlist mortality.

Pseudoaneurysm of the left main coronary artery: A complication of orbital atherectomy.

Plaque modification devices are used to treat heavily calcified coronary artery lesions during percutaneous coronary artery interventions. As these devices have unique risk profiles, clinicians need to be aware of potential complications associated with their use. A case of a contained rupture (i.e., pseudoaneurysm) of the proximal left main coronary artery following orbital atherectomy is presented. This lesion was managed with coronary artery bypass grafting and oversewing of the left main coronary artery ostium. This case illustrates that lesion location and configuration may influence tracking of these devices, as well as the actual site of tissue ablation. This case underscores the importance of concurrent imaging during treatment and concern for potential unintended consequences of atherectomy.

Pain management and safety profiles after preoperative vs postoperative thoracic epidural insertion for bilateral lung transplantation.

OBJECTIVE: Thoracic epidural analgesia provides effective pain control after lung transplantation; however, the optimal timing of placement is controversial. We sought to compare pain control and pulmonary and epidural morbidity between patients receiving preoperative vs postoperative epidurals. METHODS: Institutional records were reviewed for patients undergoing a bilateral lung transplant via a bilateral anterior thoracotomy with transverse sternotomy incision between January 2014 and January 2017. Pain control was measured using visual analog scale pain scores (0-10). Pulmonary complications included a composite of pneumonia, prolonged intubation, and reintubation/tracheostomy. RESULTS: Among 103 patients, 72 (70%) had an epidural placed preoperatively and 31 (30%) had an epidural placed within 72 hours posttransplant. There were no differences in the rates of cardiopulmonary bypass (3% vs 0%, P = 0.59); however, patients with a preoperative epidural were less likely to be placed on extracorporeal membrane oxygenation intraoperatively (25% vs 52%, P = 0.01). Pain control was similar at 24 hours (1.2 vs 1.7, P = 0.05); however, patients with a preoperative epidural reported lower pain scores at 48 (1.2 vs 2.1, P = 0.02) and 72 hours posttransplant (0.8 vs 1.7, P = 0.02). There were no differences in primary graft dysfunction (42% vs 56%, P = 0.28), length of mechanical ventilation (19.5 vs 24 hours, P = 0.18), or adverse pulmonary events (33% vs 52%, P = 0.12). No adverse events including epidural hematoma, paralysis, or infection resulted from epidural placement. CONCLUSION: Preoperative thoracic epidural placement provides improved analgesia without increased morbidity following lung transplantation.

Impella Placement Guided by Echocardiography Can Be Used as a Strategy to Unload the Left Ventricle During Peripheral Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVE: At the authors' institution, before 2015, patients cannulated for peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) did not undergo left ventricular (LV) decompression with the use of an LV vent. After 2015, the authors' institution began using the Impella device to vent the left ventricle in patients on VA-ECMO. The authors hypothesized that survival outcomes would improve in patients on VA-ECMO with the use of an Impella for LV venting. DESIGN: Retrospective, chart based review study. SETTING: Single center, university-based hospital. PARTICIPANTS: All adult patients at the authors' institution who required VA-ECMO between January 2015 and May 2017. INTERVENTION: An Impella (Abiomed, Danvers, MA) device was placed percutaneously in patients cannulated for VA-ECMO as a mechanism to provide LV venting and decompression, therefore unloading the heart. MEASUREMENTS AND MAIN RESULTS: Manual chart review was conducted, and a survival analysis was performed. It was observed that patients on VA-ECMO in whom an Impella was implanted had improved survival and an improvement in LV function as demonstrated by echocardiography compared with patients maintained on VA-ECMO alone. CONCLUSIONS: Patients on VA-ECMO plus Impella implantation demonstrated improved survival compared with patients treated with VA-ECMO alone. Key echocardiographic characteristics such as improved LV function after Impella placement and LV cavity size reduction during therapy may help predict those patients who may benefit most from this cannulation strategy.

Early structural valve deterioration and reoperation associated with the mitroflow aortic valve.

BACKGROUND: Structural valve deterioration (SVD) is a known limitation of bioprosthetic valves. Recent reports have suggested a concerning rate of early SVD in patients receiving a Mitroflow aortic bioprosthesis. We therefore compared the incidence of SVD and SVD requiring reoperation among patients receiving a Mitroflow versus a common contemporary bioprosthesis. METHODS: A retrospective cohort analysis was performed on 592 patients receiving a Mitroflow aortic bioprosthesis at our institution between 2010 and 2014. Patients were matched 1:1 using a coarsened exact matching algorithm with patients receiving a Carpentier-Edwards Magna Ease aortic bioprosthesis (Edwards Lifesciences, Irvine, CA) during the same period. The incidence of SVD (defined as a mean transprosthetic gradient ≥30 mmHg or moderate to severe intraprosthetic regurgitation), reoperation for SVD, and cumulative survival were compared between prosthesis types. RESULTS: The cumulative incidence of SVD at 5 years for all patients receiving a Mitroflow aortic bioprosthesis was 16% (13-21%) and 5% underwent reoperation for SVD. Implantation of a Mitroflow valve was associated with an increased risk of SVD compared to the comparator valve (hazard ratio [HR] 2.59 [1.69-3.98], P < 0.01). Older age had a protective effect against SVD (HR 0.95 [0.93-0.96], P < 0.01). Patients who received a Mitroflow valve had reduced long-term survival compared to those who received a comparator valve (P = 0.03). CONCLUSION: The Mitroflow aortic bioprosthesis is associated with increased rates of early SVD and reoperation for valvular dysfunction as well as reduced survival compared to a contemporary valve. Enhanced clinical and echocardiographic follow-up is advisable after Mitroflow implantation.

Mitral-valve repair versus replacement for severe ischemic mitral regurgitation.

BACKGROUND: Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited. METHODS: We randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank. RESULTS: At 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, -6.6 and -6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P=0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months. CONCLUSIONS: We observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.).

Myocyte repolarization modulates myocardial function in aging dogs.

Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions.

Cardiac transplantation from infected donors: is it safe?

BACKGROUND: Transplantation of a cardiac allograft from an infected donor risks transmission of disease to the immunocompromised recipient. Such organs are often not utilized despite little supporting evidence. We sought to evaluate outcomes following cardiac transplant with the use of an infected allograft. METHODS: The UNOS/OPTN database was used to identify first time, adult heart transplant recipients from 1995 to 2009. Patients receiving allografts from blood culture positive donor (CPD) were compared to those who did not (NCPD). RESULTS: A total of 26,813 recipients were included. Nine hundred ninety-five (3.7%) received a heart from a CPD. Recipients of hearts from CPDs were more likely to be diabetic (24% vs. 20%, p = 0.01), hypertensive (42% vs. 38%, p = 0.02), status 1 (80% vs. 76%, p = 0.0021), have a BMI > 30 (19% vs. 16%, p = 0.001), on intra-aortic balloon pump (IABP) support (7% vs. 5%, p = 0.017), and worse functional status. Recipients with a CPD were more likely to be treated for a post-transplant infection (28% vs. 23%, p = 0.003) but not for an episode of rejection in the first year after transplantation (39% vs. 40%, p = 0.73). Receipt of a CPD allograft was not a multivariate predictor for mortality. CPD and NCPD survival was similar at one year (86% vs. 87%, p = 0.2585) and 15 years (34% vs. 36%, p = 0.0929). CONCLUSION: Use of allografts from CPD has no influence on survival despite the fact that these recipients tend to have a higher acuity and more comorbidities at the time of transplantation. Utilization of a heart from a donor with a confirmed blood stream infection should be carefully considered.

Inositol 1, 4, 5-trisphosphate receptors and human left ventricular myocytes.

BACKGROUND: Little is known about the function of inositol 1,4,5-trisphosphate receptors (IP3Rs) in the adult heart experimentally. Moreover, whether these Ca(2+) release channels are present and play a critical role in human cardiomyocytes remains to be defined. IP3Rs may be activated after Gαq-protein-coupled receptor stimulation, affecting Ca(2+) cycling, enhancing myocyte performance, and potentially favoring an increase in the incidence of arrhythmias. METHODS AND RESULTS: IP3R function was determined in human left ventricular myocytes, and this analysis was integrated with assays in mouse myocytes to identify the mechanisms by which IP3Rs influence the electric and mechanical properties of the myocardium. We report that IP3Rs are expressed and operative in human left ventricular myocytes. After Gαq-protein-coupled receptor activation, Ca(2+) mobilized from the sarcoplasmic reticulum via IP3Rs contributes to the decrease in resting membrane potential, prolongation of the action potential, and occurrence of early afterdepolarizations. Ca(2+) transient amplitude and cell shortening are enhanced, and extrasystolic and dysregulated Ca(2+) elevations and contractions become apparent. These alterations in the electromechanical behavior of human cardiomyocytes are coupled with increased isometric twitch of the myocardium and arrhythmic events, suggesting that Gαq-protein-coupled receptor activation provides inotropic reserve, which is hampered by electric instability and contractile abnormalities. Additionally, our findings support the notion that increases in Ca(2+) load by IP3Rs promote Ca(2+) extrusion by forward-mode Na(+)/Ca(2+) exchange, an important mechanism of arrhythmic events. CONCLUSIONS: The Gαq-protein/coupled receptor/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias.

TandemHeart device as rescue therapy in the management of acute heart failure.

BACKGROUND: The TandemHeart device (THD) is a pump system that can be deployed percutaneously (PC) or via conventional surgical (CS) cannulation; it is capable of supporting one or both ventricles. It is a versatile system designed for use as a rescue device in acute heart failure and as a bridge to decision in moribund patients. METHODS: Retrospective analysis was conducted on all patients who underwent a THD implant; either PC or CS; at our institution. Univariate analysis was done using Fisher's exact and Chi-square tests for categorical variables and Wilcoxon Rank Sum test for continuous ones. RESULTS: 51 adult patients were identified: 10 PC and 41 CS. Mean age was 58.9 ± 12.8 years, and 31% were female. In hospital mortality was 61%. Univariate predictors of death were prolonged support (74% versus 46%, P = .04) and higher lactic acid levels (5.3 ± 4.9 versus 2.3 ± 1.9 mmol/L, P = .012). The length of stay (LOS) for survivors was 59.8 ± 30.0 days. CONCLUSION: Uni- or bi-ventricular unloading can be successfully achieved using the THD, either trans-thoracically or percutaneously, with an acceptable complication profile.

Acute rejection in donation after circulatory death (DCD) heart transplants.

BACKGROUND: Donation after circulatory death (DCD) heart transplantation has promising early survival, but the effects on rejection remain unclear. METHODS: The United Network for Organ Sharing database was queried for adult heart transplants from December 1, 2019, to December 31, 2021. Multiorgan transplants and loss to follow-up were excluded. The primary outcome was acute rejection, comparing DCD and donation after brain death (DBD) transplants. RESULTS: A total of 292 DCD and 5,582 DBD transplants met study criteria. Most DCD transplants were transplanted at status 3-4 (61.0%) compared to 58.6% of DBD recipients at status 1-2. DCD recipients were less likely to be hospitalized at transplant (26.7% vs 58.3%, p < 0.001) and to require intra-aortic balloon pumping (IABP; 9.6% vs 28.9%, p < 0.001), extracorporeal membrane oxygenation (ECMO; 0.3% vs 5.9%, p < 0.001) or temporary left ventricular assist device (LVAD; 1.0% vs 2.7%, p < 0.001). DCD recipients were more likely to have acute rejection prior to discharge (23.3% vs 18.4%, p = 0.044) and to be hospitalized for rejection (23.4% vs 11.4%, p = 0.003) at a median follow-up of 15 months; the latter remained significant after propensity matching. On multivariable logistic regression, DCD donation was an independent predictor of acute rejection (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.00-2.15, p = 0.048) and hospitalization for rejection (OR 2.03, 95% CI 1.06-3.70, p = 0.026). On center-specific subgroup analysis, DCD recipients continued to have higher rates of hospitalization for rejection (23.4% vs 13.8%, p = 0.043). CONCLUSIONS: DCD recipients are more likely to experience acute rejection. Early survival is similar between DCD and DBD recipients, but long-term implications of increased early rejection in DCD recipients require further investigation.