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Background: Little is known about the relationship between cytomegalovirus (CMV) infections and donor‐derived cell‐free DNA (dd‐cfDNA) in heart transplant recipients. Methods: In our study, CMV and dd‐cfDNA results were prospectively collected on single‐organ heart transplant recipients. If the CMV study was positive, a CMV study with dd‐cfDNA was repeated 1‐3 months later. The primary aim was to compare dd‐cfDNA between patients with positive and negative CMV results. Results: Of 44 patients enrolled between August 2022 and April 2023, 12 tested positive for CMV infections, 25 were included as controls, and seven patients with a viral infection without CMV were excluded. Baseline characteristics did not differ significantly between CMV‐positive and CMV‐negative patients with the exception of a later median time post‐transplant in the CMV‐positive group (253 days vs. 120 days, p =.03). Dd‐cfDNA levels were significantly higher in patients with CMV infections compared to those without (p <.001) with more patients in the CMV positive group showing dd‐cfDNA results ≥.12% (75% vs. 8%, p <.001) and ≥.20% (58% vs. 8%, p =.002). Each 1 log10 copy/ml reduction in CMV viral load from visit 1 to visit 2 was associated with a.23% reduction in log10 dd‐cfDNA (p =.002). Conclusion: Our findings suggest that active CMV infections may raise dd‐cfDNA levels in patients following heart transplantation. Larger studies are needed to validate these preliminary findings. [ABSTRACT FROM AUTHOR]

Background: Recent innovations in temperature‐controlled cardiac transportation allow for static hypothermic preservation of transplant organs during transportation. We assessed differences in donor‐derived cell‐free DNA (dd‐cfDNA) using the SherpaPak cardiac transport system (SCTS) and traditional ice transportation. Methods: Single‐organ heart transplant recipients between January 2020 and January 2022 were included if they had dd‐cfDNA measures ≤6 weeks post‐transplant along with the baseline biopsy at 6 weeks as part of the surveillance protocol and no biopsy‐confirmed rejection ≤90 days. Elevated dd‐cfDNA ≥.20% were compared between groups using logistic regression including a subject effect. Results: Of 65 hearts transplanted, 30 were transported with SCTS and 35 on ice. Recipient characteristics were similar between groups. Donors in the SCTS group were older (34 vs. 40 years, p =.04) with a longer total ischemic time (171 vs. 212 min, p =.002). Recipients in the SCTS group had a greater risk of elevated dd‐cfDNA unadjusted and adjusted for donor age, and prolonged ischemic times > 3.5 h (Unadjusted odds ratio: 4.9, 95%‐CI: 1.08–22.5, p =.039 and Adjusted odds ratio: 5.5, 95%‐CI: 1.03–29.6, p =.046). Primary graft dysfunction rates and 1‐year mortality were comparable between groups. Conclusion: Elevated dd‐cfDNA in patients procured with SCTS may indicate that graft injury was not negated relative to ice transport. However, there were no clinical differences noted in short or long‐term outcomes including mortality despite a longer ischemic time in the SCTS group. [ABSTRACT FROM AUTHOR]

Background: Right ventricular failure is associated with increased morbidity and mortality. The ProtekDuo (Livanova, Uk) is a dual‐lumen cannula that allows for percutaneous right ventricular support and may be connected to a centrifugal blood pump such as the TandemHeart or LifeSparc (Livanova, UK). This systematic review aims to evaluate the safety and efficacy of ProtekDuo right ventricular support and evaluate potential clinical variables that can influence outcomes. Methods: PubMed, MEDLINE, SCOPUS, EMBASE, and the Cochrane Library were systematically searched. Studies meeting inclusion criteria, where ProtekDuo was used as the right ventricular assist device with reported numerical death counts for mortality as outcome measures. The primary endpoints were in‐hospital 30‐day and 1‐year mortality rates. Secondary endpoints included ICU length of stay, conversion rates to surgical RVADs, ProtekDuo wean rates, duration of use of ProtekDuo, and adverse event rates. Results: Of 49 studies reviewed, 7 met inclusion criteria with study periods between October 2014 and November 2019. ProtekDuo was utilized due to RV failure post‐LVAD insertion in 64.8% (68/105) of patients. In‐hospital mortality, 30‐day mortality, and 1‐year mortality ranged between 9%–46%, 15%–40%, and 19%–40%, respectively. Weaning from ProtekDuo and conversion to surgical RVAD ranged between 24%–91% and 11%–35%, respectively. The ICU stay average ranged from 15.8 to 36 days and ProtekDuo mean support duration ranged from 10.5 to 58 days. Conclusion: The ProtekDuo cannula is increasingly utilized as a right ventricular support device. Despite the sparse retrospective data available with variable patient characteristics and study design, percutaneous RV mechanical support via ProtekDuo cannula is a safe and feasible option. [ABSTRACT FROM AUTHOR]

Heart and lung transplant recipients require care provided by clinicians from multiple different specialties, each contributing unique expertise and perspective. The period the patient spends in the intensive care unit is one of the most critical times in the perioperative trajectory. Various organizational models of intensive care exist, including those led by intensivists, surgeons, transplant cardiologists, and pulmonologists. Coordinating timely efficient intensive care is an essential and logistically difficult goal. The present work product of the American Society of Transplantation's Thoracic and Critical Care Community of Practice, Critical Care Task Force outlines operational guidelines and principles that may be applied in different organizational models to optimize the delivery of intensive care for the cardiothoracic organ recipient. [ABSTRACT FROM AUTHOR]

Critical care, heart disease, lung disease Keywords: critical care; heart disease; lung disease EN critical care heart disease lung disease 1 3 3 04/13/23 20230401 NES 230401 The ability to promptly recognize and manage complications following cardiac surgery is closely associated with operative mortality,[1] and there has been increasing interest in the impact of intensive care unit (ICU) staffing models on post-operative care.[[2], [4]] Thoracic transplant recipients have particularly complex peri-operative care needs necessitating a multidisciplinary approach, yet there is limited information on existing ICU structure and staffing models for these patients in current practice. In total, 17 (60.7%) respondents were critical care board certified, and 6 (50%) anesthesiologists were dual trained in critical care and cardiac anesthesia. [Extracted from the article]

Donor‐derived cell free DNA (dd‐cfDNA) has rapidly become part of rejection surveillance following orthotopic heart transplantation. However, some patients show elevated dd‐cfDNA without clinical evidence of rejection. With the aim to provide a clinical description of this subpopulation, we retrospectively analyzed 35 cardiac transplant recipients at our center who experienced elevated (≥.20%) dd‐cfDNA in the absence of clinical rejection, out of a total 106 recipients who had dd‐cfDNA results available during the first year. The median time to first elevated dd‐cfDNA level was 46 days, and the highest dd‐cfDNA recorded within 1 year was.31% [inter‐quartile range,.23–.45]. Twenty‐two (63%) patients experienced infections (cytomegalovirus (CMV) or other), and 16 (46%) presented with de novo donor‐specific antibodies. Cluster analysis revealed four distinct groups characterized by (a) subclinical rejection with 50% CMV (n = 16), (b) non‐CMV infections and the longest time to first elevated dd‐cfDNA (187 days) (n = 8), (c) right ventricular dysfunction (n = 6), and (d) women who showed the youngest median age (45 years) and highest median dd‐cfDNA (.50%) (n = 5). Continued prospective analysis is needed to determine if these observations warrant changes in patient management to optimize the utilization of this vital non‐invasive graft surveillance tool. [ABSTRACT FROM AUTHOR]

Extended‐release tacrolimus for prophylaxis of allograft rejection in orthotopic heart transplant (OHT) recipients is currently not FDA‐approved. One such extended‐release formulation of tacrolimus known as LCPT allows once‐daily dosing and improves bioavailability compared to immediate‐release tacrolimus (IR‐tacrolimus). We compared the efficacy and safety of LCPT to IR‐tacrolimus applied de novo in adult OHT recipients. Twenty‐five prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR‐tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 1 year was compared using non‐inferiority analysis. LCPT demonstrated non‐inferiority to IR‐tacrolimus, with a primary outcome risk reduction of 20% (90% CI: ‐40%, ‐.5%; non‐inferiority P =.001). Tacrolimus trough levels peaked at 2–3 months and were higher in LCPT (median 14.5 vs. 12.7 ng/ml; P =.03) with similar dose levels (LCPT vs. IR‐tacrolimus:.08 vs..09 mg/kg/day; P =.33). Cardiovascular‐related readmissions were reduced by 62% (P =.046) in LCPT patients. The complication rate per transplant admission and all‐cause readmission rate did not differ significantly. These results suggest that LCPT is non‐inferior in efficacy to IR‐tacrolimus with a similar safety profile and improved bioavailability in OHT. [ABSTRACT FROM AUTHOR]

Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid, is a highly effective immunosuppressive agent in heart transplant therapy. While the FDA approved dose is 1500 mg twice daily, dosing is often reduced due to dose‐dependent adverse effects. However, empiric MMF dose reductions may lead to sub‐therapeutic dosing and impair clinical outcomes. Our single center protocolized a risk‐stratified approach based on age and weight to dose 500 mg twice daily or 1000 mg twice daily to patients after heart transplantation. This retrospective single‐center study analyzed 140 consecutive heart transplant patients who were initiated on our risk‐stratified MMF protocol post‐transplant. The analysis revealed that the composite rate of biopsy‐proven rejection, graft loss, or mortality at 1‐year post‐transplantation was similar between the two groups. Incidence of neutropenia, thrombocytopenia, infection, cardiac allograft vasculopathy, or acute kidney injury by 1‐year also showed similar results between the two groups. Risk‐stratification of MMF dosing appears to be a safe and effective strategy after heart transplantation. [ABSTRACT FROM AUTHOR]

Aim: The MOMENTUM 3 pivotal trial established superiority of the HeartMate 3 (HM3) left ventricular assist device (LVAD), a fully magnetically levitated centrifugal-flow pump, over the HeartMate II axial-flow pump. We now evaluate HM3 LVAD outcomes in a single-arm prospective continuous access protocol (CAP) post-pivotal trial study.Methods and Results: We enrolled 2200 HM3 implanted patients (515 pivotal trial and 1685 CAP patients) and compared outcomes including survival free of disabling stroke or reoperation to replace or remove a malfunctioning device (primary composite endpoint), overall survival and major adverse events at 2 years. The 2-year primary endpoint [76.7% vs. 74.8%; adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.71-1.08, P = 0.21] and overall survival (81.2% vs. 79.0%) were similar among CAP and pivotal cohorts despite sicker patients (more intra-aortic balloon pump use and INTERMACS profile 1) in CAP who were more often intended for destination therapy. Survival was similar between the CAP and pivotal trial in transplant ineligible patients (79.1% vs. 76.7%; adjusted HR 0.89, 95% CI 0.68-1.16, P = 0.38). In a pooled analysis, the 2-year primary endpoint was similar between INTERMACS profiles 1-2 ('unstable' advanced heart failure), profile 3 ('stable' on inotropic therapy), and profiles 4-7 ('stable' ambulatory advanced heart failure) (75.7% vs. 77.6% vs. 72.9%, respectively). The net burden of adverse events was lower in CAP (adjusted rate ratio 0.93, 95% CI 0.88-0.98, P = 0.006), with consequent decrease in hospitalization.Conclusions: The primary results of accumulating HM3 LVAD experience suggest a lower adverse event burden and similar survival compared to the pivotal MOMENTUM 3 trial. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) have improved clinical outcomes and quality of life for those with end‐stage heart failure. However, the costs and risks associated with these devices necessitate appropriate patient selection. LVAD candidates are becoming increasingly more obese and there are conflicting reports regarding obesity's effect on outcomes. Hence, we sought to evaluate the impact of extreme obesity on clinical outcomes after LVAD placement. Consecutive LVAD implantation patients at our center from June 2008 to May 2016 were studied retrospectively. We compared patients with a body mass index (BMI) ≥40 kg/m2 (extremely obese) to those with BMI < 40 kg/m2 with respect to patient characteristics and surgical outcomes, including survival. 252 patients were included in this analysis, 30 (11.9%) of whom met the definition of extreme obesity. We found that patients with extreme obesity were significantly younger (47[33, 57] vs. 60[52, 67] years, P < 0.001) with fewer prior sternotomies (16.7% vs. 36.0%, P = 0.04). They had higher rates of pump thrombosis (30% vs. 9.0%, P = 0.003) and stage 2/3 acute kidney injury (46.7% vs. 27.0%, P = 0.003), but there were no differences in 30‐day or 1‐year survival, even after adjusting for age and clinical factors. Extreme obesity does not appear to place LVAD implantation patients at a higher risk for mortality compared to those who are not extremely obese; however, extreme obesity was associated with an increased risk of pump thrombosis, suggesting that these patients may require additional care to reduce the need for urgent device exchange. [ABSTRACT FROM AUTHOR]

Abstract: Donor sequence number (DSN) represents the number of candidates to whom a graft was offered and declined prior to acceptance for transplantation. We sought to investigate the outcomes of patients receiving high DSN grafts. Consecutive isolated adult cardiac transplantations performed at a single‐center were reviewed. Recipients were grouped into standard (≤75th percentile) DSN and high (>75th percentile) DSN. A previously validated donor risk index was used to quantify the risk associated with donor grafts, and recipient outcomes were assessed. Overall, 254 patients were included: 194 standard DSN (range 1‐79) and 60 high DSN (range 82‐1723). High DSN grafts were harvested at greater distance (P < .001) with increased ischemia time (P < .001), resulting in a modest increase in donor risk index (1 point median difference, P = .014). High DSN recipients were less frequently listed as UNOS status 1A (P < .001). Despite a nonsignificant trend toward increased in‐hospital/30‐day mortality in high DSN recipients, there were no differences in primary graft dysfunction or 1‐year survival (high DSN 89% vs standard DSN 88%, P = .82). After adjustment for risk factors, high DSN was not associated with increased 1‐year mortality (hazard ratio 1.18, 95%‐CI 0.54‐2.58, P = .68). [ABSTRACT FROM AUTHOR]

Abstract: Ventricular tachycardia (VT) commonly occurs in patients with ischemic or nonischemic cardiomyopathy and requires antiarrhythmic drugs, ablation, or advanced circulatory support. However, life‐threatening VT may be refractory to these therapies, and may cause frequent implantable cardioverter defibrillator (ICD) discharges. Left cardiac sympathetic denervation reduces the occurrence of these fatal arrhythmias by inhibiting the sympathetic outflow to the cardiac tissue. We present a 69‐year‐old man with nonischemic cardiomyopathy, life‐threatening VT, and hemodynamic instability with numerous ICD discharges, who remained refractory to antiarrhythmic drug therapy and ablation attempts. He was effectively treated with bilateral cardiac sympathectomy. Six months later, he remained free of VT with no ICD discharges. [ABSTRACT FROM AUTHOR]