Extended ischemic time (>15 hours) using controlled hypothermic storage in lung transplantation: A multicenter experience.

Static ice storage has long been the standard-of-care for lung preservation, although freezing injury limits ischemic time (IT). Controlled hypothermic storage (CHS) at elevated temperature could safely extend IT. This retrospective analysis assesses feasibility and safety of CHS with IT > 15 hours. Three lung transplant (LuTx) centers (April-October 2023) included demographics, storage details, IT, and short-term outcome from 13 LuTx recipients (8 male, 59 years old). Donor lungs were preserved in a portable CHS device at 7 (5-9.3)°C. Indication was overnight bridging and/or long-distance transport. IT of second-implanted lung was 17.3 (15.1-22) hours. LuTx were successful, 4/13 exhibited primary graft dysfunction grade 3 within 72 hours and 0/13 at 72 hours. Post-LuTx mechanical ventilation was 29 (7-442) hours. Intensive care unit stay was 9 (5-28) and hospital stay 30 (16-90) days. Four patients needed postoperative extracorporeal membrane oxygenation (ECMO). One patient died (day 7) following malpositioning of an ECMO cannula. This multicenter experience demonstrates the possibility of safely extending IT > 15 hours by CHS.

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.

Is Transplantation With Coronavirus Disease 2019-Positive Donor Lungs Safe? A US Nationwide Analysis.

BACKGROUND: Since the beginning of the pandemic, coronavirus disease 2019 (COVID-19) has caused debilitating lung failure in many patients. Practitioners have understandably been hesitant to use lungs from donors with COVID-19 for transplantation. This study aimed to analyze the characteristics and short-term outcomes of lung transplantation from donors with recent positive COVID-19 testing results. METHODS: Lung transplantations performed between January 2020 and June 2022 were queried from the United Network for Organ Sharing database. Pediatric, multiorgan, and repeat lung transplantations were excluded. Propensity scoring matched recipients of lungs from donors with recent positive COVID-19 testing results to recipients of lungs from donors with negative COVID-19 testing results, and comparisons of 30-day mortality, 3-month mortality, and perioperative outcomes were performed. RESULTS: A total of 5270 patients underwent lung transplantation during the study dates, including 51 patients who received lungs from donors with recent positive COVID-19 testing results. Forty-five recipients of lungs from donors with recent positive COVID-19 testing results were matched with 135 recipients of lungs from donors with negative COVID-19 testing results. After matching, there was no difference in 30-day (log-rank P = .42) and 3-month (log-rank P = .42) mortality. The incidence of other perioperative complications was similar between the groups. CONCLUSIONS: The 30-day and 3-month survival outcomes were similar between recipients of lungs from donors with recent positive COVID-19 testing results and recipients of lungs from donors with negative COVID-19 testing results. This finding suggests that highly selected COVID-19-positive donors without evidence of active infection may be safely considered for lung transplantation. Further studies should explore long-term outcomes to provide reassurance about the safety of this practice.

Building a successful minimally invasive mitral valve repair program before introducing the robotic approach: The Massachusetts General Hospital experience.

Background: Patients with mitral valve prolapse (MVP) requiring surgical repair (MVr) are increasingly operated using minimally invasive strategies. Skill acquisition may be facilitated by a dedicated MVr program. We present here our institutional experience in establishing minimally invasive MVr (starting in 2014), laying the foundation to introduce robotic MVr. Methods: We reviewed all patients that had undergone MVr for MVP via sternotomy or mini-thoracotomy between January 2013 and December 2020 at our institution. In addition, all cases of robotic MVr between January 2021 and August 2022 were analyzed. Case complexity, repair techniques, and outcomes are presented for the conventional sternotomy, right mini-thoracotomy and robotic approaches. A subgroup analysis comparing only isolated MVr cases via sternotomy vs. right mini-thoracotomy was conducted using propensity score matching. Results: Between 2013 and 2020, 799 patients were operated for native MVP at our institution, of which 761 (95.2%) received planned MVr (263 [34.6%] via mini-thoracotomy) and 38 (4.8%) received planned MV replacement. With increasing proportions of minimally invasive procedures (2014: 14.8%, 2020: 46.5%), we observed a continuous growth in overall institutional volume of MVP (n = 69 in 2013; n = 127 in 2020) and markedly improved institutional rates of successful MVr, with 95.4% in 2013 vs. 99.2% in 2020. Over this period, a higher complexity of cases were treated minimally-invasively and increased use of neochord implantation ± limited leaflet resection was observed. Patients operated minimally invasively had longer aortic cross-clamp times (94 vs. 88 min, p = 0.001) but shorter ventilation times (4.4 vs. 4.8 h, p = 0.002) and hospital stays (5 vs. 6 days, p < 0.001) than those operated via sternotomy, with no significant differences in other outcome variables. A total of 16 patients underwent robotically assisted MVr with successful repair in all cases. Conclusion: A focused approach towards minimally invasive MVr has transformed the overall MVr strategy (incision; repair techniques) at our institution, leading to a growth in MVr volume and improved repair rates without significant complications. On this foundation, robotic MVr was first introduced at our institution in 2021 with excellent outcomes. This emphasizes the importance of building a competent team to perform these challenging operations, especially during the initial learning curve.

Impact of Moderate Aortic Stenosis in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Afterload from moderate aortic stenosis (AS) may contribute to adverse outcomes in patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: The authors evaluated clinical outcomes in patients with HFrEF and moderate AS relative to those without AS and with severe AS. METHODS: Patients with HFrEF, defined by left ventricular ejection fraction (LVEF) <50% and no, moderate, or severe AS were retrospectively identified. The primary endpoint, defined as a composite of all-cause mortality and heart failure (HF) hospitalization, was compared across groups and within a propensity score-matched cohort. RESULTS: We included 9,133 patients with HFrEF, of whom 374 and 362 had moderate and severe AS, respectively. Over a median follow-up time of 3.1 years, the primary outcome occurred in 62.7% of patients with moderate AS vs 45.9% with no AS (P < 0.0001); rates were similar with severe and moderate AS (62.0% vs 62.7%; P = 0.68). Patients with severe AS had a lower incidence of HF hospitalization (36.2% vs 43.6%; P < 0.05) and were more likely to undergo AVR within the follow-up period. Within a propensity score-matched cohort, moderate AS was associated with an increased risk of HF hospitalization and mortality (HR: 1.24; 95% CI: 1.04-1.49; P = 0.01) and fewer days alive outside of the hospital (P < 0.0001). Aortic valve replacement (AVR) was associated with improved survival (HR: 0.60; CI: 0.36-0.99; P < 0.05). CONCLUSIONS: In patients with HFrEF, moderate AS is associated with increased rates of HF hospitalization and mortality. Further investigation is warranted to determine whether AVR in this population improves clinical outcomes.

Induction therapy in lung transplantation: A contemporary analysis of trends and outcomes.

OBJECTIVES: We provide a contemporary consideration of long-term outcomes and trends of induction therapy use following lung transplantation in the United States. METHODS: We reviewed the United Network for Organ Sharing registry from 2006 to 2018 for first-time, adult, lung-only transplant recipients. Long-term survival was compared between induction classes (Interleukin-2 inhibitors, monoclonal or polyclonal cell-depleting agents, and no induction therapy). A 1:1 propensity score match was performed, pairing patients who received basiliximab with similar risk recipients who did not receive induction therapy. Outcomes in matched populations were compared using Cox, Kaplan-Meier and Logistic regression modeling. MEASUREMENTS AND MAIN RESULTS: 22 025 recipients were identified; 8003 (36.34%) were treated with no induction therapy, 11 045 (50.15%) with basiliximab, 1556 (7.06%) with alemtuzumab and 1421 (6.45%) with anti-thymocyte globulin. Compared with those who received no induction, patients receiving basiliximab, alemtuzumab or anti-thymocyte globulin were found on multivariable Cox-regression analyses to have lower long-term mortality (all p < .05). Following propensity score matching of basiliximab and no induction populations, analyses demonstrated a statistically significant association between basiliximab use and long- term survival (p < .001). Basiliximab was also associated with a lower risk of acute rejection (p < .001) and renal failure (p = .002). CONCLUSION: Induction therapy for lung transplant recipients-specifically basiliximab-is associated with improved long-term survival and a lower risk of renal failure or acute rejection.

Patient- and Process-Related Contributors to the Underuse of Aortic Valve Replacement and Subsequent Mortality in Ambulatory Patients With Severe Aortic Stenosis.

Background Many patients with severe aortic stenosis (AS) and an indication for aortic valve replacement (AVR) do not undergo treatment. The reasons for this have not been well studied in the transcatheter AVR era. We sought to determine how patient- and process-specific factors affected AVR use in patients with severe AS. Methods and Results We identified ambulatory patients from 2016 to 2018 demonstrating severe AS, defined by aortic valve area [Formula: see text]1.0 cm2. Propensity scoring analysis with inverse probability of treatment weighting was used to evaluate associations between predictors and the odds of undergoing AVR at 365 days and subsequent mortality at 730 days. Of 324 patients with an indication for AVR (79.3±9.7 years, 57.4% men), 140 patients (43.2%) did not undergo AVR. The odds of AVR were reduced in patients aged >90 years (odds ratio [OR], 0.24 [95% CI, 0.08-0.69]; P=0.01), greater comorbid conditions (OR, 0.88 per 1-point increase in Combined Comorbidity Index [95% CI, 0.79-0.97]; P=0.01), low-flow, low-gradient AS with preserved left ventricular ejection fraction (OR, 0.11 [95% CI, 0.06-0.21]), and low-gradient AS with reduced left ventricular ejection fraction (OR, 0.18 [95% CI, 0.08-0.40]) and were increased if the transthoracic echocardiogram ordering provider was a cardiologist (OR, 2.46 [95% CI, 1.38-4.38]). Patients who underwent AVR gained an average of 85.8 days of life (95% CI, 40.9-130.6) at 730 days. Conclusions The proportion of ambulatory patients with severe AS and an indication for AVR who do not receive AVR remains significant. Efforts are needed to maximize the recognition of severe AS, especially low-gradient subtypes, and to encourage patient referral to multidisciplinary heart valve teams.

Trends in Utilization of Aortic Valve Replacement for Severe Aortic Stenosis.

BACKGROUND: Despite the rapid growth of aortic valve replacement (AVR) for aortic stenosis (AS), limited data suggest symptomatic severe AS remains undertreated. OBJECTIVES: This study sought to investigate temporal trends in AVR utilization among patients with a clinical indication for AVR. METHODS: Patients with severe AS (aortic valve area <1 cm2) on transthoracic echocardiograms from 2000 to 2017 at 2 large academic medical centers were classified based on clinical guideline indications for AVR and divided into 4 AS subgroups: high gradient with normal left ventricular ejection fraction (LVEF) (HG-NEF), high gradient with low LVEF (HG-LEF), low gradient with normal LVEF (LG-NEF), and low gradient with low LVEF (LG-LEF). Utilization of AVR was examined and predictors identified. RESULTS: Of 10,795 patients, 6,150 (57%) had an indication or potential indication for AVR, of whom 2,977 (48%) received AVR. The frequency of AVR varied by AS subtype with LG groups less likely to receive an AVR (HG-NEF: 70%, HG-LEF: 53%, LG-NEF: 32%, LG-LEF: 38%, P < 0.001). AVR volumes grew over the 18-year study period but were paralleled by comparable growth in the number of patients with an indication for AVR. In patients with a Class I indication, younger age, coronary artery disease, smoking history, higher hematocrit, outpatient index transthoracic echocardiogram, and LVEF ≥0.5 were independently associated with an increased likelihood of receiving an AVR. AVR was associated with improved survival in each AS-subgroup. CONCLUSIONS: Over an 18-year period, the proportion of patients with an indication for AVR who did not receive AVR has remained substantial despite the rapid growth of AVR volumes.

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.

Influence of left ventricular ejection fraction on morbidity and mortality after aortic root replacement.

OBJECTIVE: To better understand morbidity and mortality in patients with a low left ventricular ejection fraction (LVEF) undergoing aortic root replacement. METHODS: All patients who underwent aortic root replacement at our institution between 2005 and 2013 (n = 595) were retrospectively reviewed and included in the study. The primary outcome was mortality. Secondary outcomes were in-hospital mortality and perioperative morbidity. Restricted cubic spline analysis showed a relatively linear inverse relationship between LVEF and the hazard ratio for mortality in patients with an LVEF <50% with no unique cutoff. Therefore, LVEF was treated as a continuous variable. Patients were divided into 3 groups (LVEF <40%, LVEF 40%-49%, and LVEF ≥50%) in order to illustrate the impact of LVEF on mortality. RESULTS: LVEF <40% patients had greater in-hospital mortality (14.0% vs 5.0% vs 1.0%, P < .001) and longer median hospital and intensive care unit stays (10.5 vs 8 vs 6 days, P < .001 and 4 vs 2 vs 2 days, P < .001) than patients with LVEF 40% to 49% or greater than 50%, respectively. Patients with LVEF <40% had more reoperations for bleeding (18% vs 5.0% vs 5.8%, P = .004), postoperative respiratory failure (16% vs 6.7% vs 4.9%, P = .008), and need for mechanical circulatory support (8.0% vs 5.0% vs 1.4%, P = .005). Using multivariable Cox proportional hazards analysis, we found that reduced LVEF, age, previous, cardiac surgery, and type A dissection were independent predictors of mortality. CONCLUSIONS: Reduced LVEF negatively impacts mortality as well as in-hospital death and perioperative morbidity after aortic root replacement. Careful patient selection and risk discussion are vital in this high-risk population.

Ascending aorta, aortic arch and supra-aortic vessels rupture in blunt thoracic trauma.

Surgical strategy and long-term outcomes of patients with rupture of the ascending aorta, aortic arch and supra-aortic vessels following blunt thoracic trauma have been rarely reported. We reviewed our institutional experience between 1995 and 2016. We identified 2 patients with an innominate artery ruptures, 2 with an aortic arch ruptures and 1 with an ascending aorta rupture; all were induced by the posterior displacement of the anterior chest wall. All patients underwent open surgical repair. Cardiopulmonary bypass with antegrade cerebral perfusion was required in 2 cases. All patients were alive at the end of the follow-up (median 18 months; from 3 to 180 months) including 1 patient with cortical blindness.

Injuries to the Aorta, Aortic Annulus, and Left Ventricle During Transcatheter Aortic Valve Replacement: Management and Outcomes.

The experience with transcatheter aortic valve replacement is increasing worldwide; however, the incidence of potentially catastrophic cardiac or aortic complications has not decreased. In most cases, significant injuries to the aorta, aortic valve annulus, and left ventricle require open surgical repair. However, the transcatheter aortic valve replacement patient presents a unique challenge as many patients are at high or prohibitive surgical risk and, therefore, an open surgical procedure may not be feasible or appropriate. Consequently, prevention of these potentially catastrophic injuries is vital, and practitioners need to understand when open surgical repair is required and when alternative management strategies can be used. The goal of this article is to provide an overview of current management and prevention strategies for major complications involving the aorta, aortic valve annulus, and left ventricle.

Abnormal pulmonary endothelial cells may underlie the enigmatic pathogenesis of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension results from chronic mechanical obstruction of the pulmonary arteries after acute venous thromboembolism. However, the mechanisms that result in the progression from unresolved thrombus to fibrotic vascular remodeling are unknown. We hypothesized that pulmonary artery endothelial cells contribute to this phenomenon via paracrine growth factor and cytokine signaling. METHODS: Using enzyme-linked immunosorbent assay and cell migration assays, we investigated the circulating growth factors and cytokines of chronic thromboembolic pulmonary hypertension patients as well as the cross talk between pulmonary endothelial cells and pulmonary artery smooth muscle cells and monocytes from patients with chronic thromboembolic pulmonary hypertension in vitro. RESULTS: Culture medium from the pulmonary endothelial cells of chronic thromboembolic pulmonary hypertension patients contained higher levels of growth factors (fibroblast growth factor 2), inflammatory cytokines (interleukin 1ß, interleukin 6, monocyte chemoattractant protein 1), and cell adhesion molecules (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1). Furthermore, exposure to the culture medium of pulmonary endothelial cells from patients with chronic thromboembolic pulmonary hypertension elicited marked pulmonary artery smooth muscle cell growth and monocyte migration. CONCLUSIONS: These findings implicate pulmonary endothelial cells as key regulators of pulmonary artery smooth muscle cell and monocyte behavior in chronic thromboembolic pulmonary hypertension and suggest a potential mechanism for the progression from unresolved thrombus to fibrotic vascular remodeling.