Four decades of progress in heart-lung transplantation: Two hundred seventy-one cases at a single institution.

OBJECTIVE: The objective of this study is to evaluate survival for combined heart-lung transplant (HLTx) recipients across 4 decades at a single institution. We aim to summarize our contemporary practice based on more than 271 HLTx procedures over 40 years. METHODS: Data were collected from a departmental database and the United Network for Organ Sharing. Recipients younger than age 18 years, those undergoing redo HLTx, or triple-organ system transplantation were excluded, leaving 271 patients for analysis. The pioneering era was defined by date of transplant between 1981 and 2000 (n = 155), and the modern era between 2001 and 2022 (n = 116). Survival analysis was performed using cardinality matching of populations based on donor and recipient age, donor and recipient sex, ischemic time, and sex matching. RESULTS: Between 1981 and 2022, 271 HLTx were performed at a single institution. Recipients in the modern era were older (age 42 vs 34 y; P < .001) and had shorter waitlist times (78 vs 234 days; P < .001). Allografts from female donors were more common in the modern era (59% vs 39%; P = .002). In the matched survival analysis, 30-day survival (97% vs 84%; P = .005), 1-year survival (89% vs 77%; P = .041), and 10-year survival (53% vs 26%; P = .012) significantly improved in the modern era relative to the pioneering era, respectively. CONCLUSIONS: Long-term survival in HLTx is achievable with institutional experience and may continue to improve in the coming decades. Advances in mechanical circulatory support, improved maintenance immunosuppression, and early recognition and management of acute complications such as primary graft dysfunction and acute rejection have dramatically improved the prognosis for recipients of HLTx in our contemporary institutional experience.

Surgical Management of Esophageal Perforation: Examining Trends in a Multi-Institutional Cohort.

BACKGROUND: Esophageal perforations historically are associated with significant morbidity and mortality and generally require emergent intervention. The influence of improved diagnostic and therapeutic modalities available in recent years on management has not been examined. This study examined the surgical treatments and outcomes of a modern cohort. METHODS: Patients with esophageal perforation management in the 2005-2020 American College of Surgeons National Surgical Quality Improvement Program database were stratified into three eras (2005-2009, 2010-2014, and 2015-2020). Surgical management was classified as primary repair, resection, diversion, or drainage alone based on procedure codes. The distribution of procedure use, morbidity, and mortality across eras was examined. RESULTS: Surgical management of 378 identified patients was primary repair (n=193,51%), drainage (n=89,24%), resection (n=70,18%), and diversion (n=26,7%). Thirty-day mortality in the cohort was 9.5% (n=36/378) and 268 patients (71%) had at least one complication. The median length of stay was 15 days. Both morbidity (Era 1 65% [n=42/60] versus Era 2 69% [n=92/131] versus Era 3 72% [n=135/187], p=0.3) and mortality (Era 1 11% [n=7/65] versus Era 2 9% [n=12/131] versus Era 3 10% [n=19/187], p=0.9) did not change significantly over the three defined eras. Treatment over time evolved such that primary repair was more frequently utilized (43% in Era 1 to 51% in Era 3) while diversion was less often performed (13% in Era 1 to 7% in Era 3) (p=0.009). CONCLUSIONS: Esophageal perforation management in recent years uses diversion less often but remains associated with significant morbidity and mortality.

Lineage-Specific Induced Pluripotent Stem Cell-Derived Smooth Muscle Cell Modeling Predicts Integrin Alpha-V Antagonism Reduces Aortic Root Aneurysm Formation in Marfan Syndrome Mice.

BACKGROUND: The role of increased smooth muscle cell (SMC) integrin αv signaling in Marfan syndrome (MFS) aortic aneurysm remains unclear. Herein, we examine the mechanism and potential efficacy of integrin αv blockade as a therapeutic strategy to reduce aneurysm progression in MFS. METHODS: Induced pluripotent stem cells (iPSCs) were differentiated into aortic SMCs of the second heart field (SHF) and neural crest (NC) lineages, enabling in vitro modeling of MFS thoracic aortic aneurysms. The pathological role of integrin αv during aneurysm formation was confirmed by blockade of integrin αv with GLPG0187 in Fbn1C1039G/+ MFS mice. RESULTS: iPSC-derived MFS SHF SMCs overexpress integrin αv relative to MFS NC and healthy control SHF cells. Furthermore, integrin αv downstream targets (FAK [focal adhesion kinase]/AktThr308/mTORC1 [mechanistic target of rapamycin complex 1]) were activated, especially in MFS SHF. Treatment of MFS SHF SMCs with GLPG0187 reduced p-FAK/p-AktThr308/mTORC1 activity back to control SHF levels. Functionally, MFS SHF SMCs had increased proliferation and migration compared to MFS NC SMCs and control SMCs, which normalized with GLPG0187 treatment. In the Fbn1C1039G/+ MFS mouse model, integrin αv, p-AktThr308, and downstream targets of mTORC1 proteins were elevated in the aortic root/ascending segment compared to littermate wild-type control. Mice treated with GLPG0187 (age 6-14 weeks) had reduced aneurysm growth, elastin fragmentation, and reduction of the FAK/AktThr308/mTORC1 pathway. GLPG0187 treatment reduced the amount and severity of SMC modulation assessed by single-cell RNA sequencing. CONCLUSIONS: The integrin αv-FAK-AktThr308 signaling pathway is activated in iPSC SMCs from MFS patients, specifically from the SHF lineage. Mechanistically, this signaling pathway promotes SMC proliferation and migration in vitro. As biological proof of concept, GLPG0187 treatment slowed aneurysm growth and p-AktThr308 signaling in Fbn1C1039G/+ mice. Integrin αv blockade via GLPG0187 may be a promising therapeutic approach to inhibit MFS aneurysmal growth.

Midterm Outcomes in Type A Aortic Dissection Repair With and Without Malperfusion in a Hybrid Operating Room.

Treatment approach to type A aortic dissection with malperfusion, immediate open aortic repair vs upfront endovascular treatment, remains controversial. From January 2017 to July 2021, 301 consecutive type A repairs were evaluated at our institution. Starting in 2019, all type A aortic dissections were performed in a fixed-fluoroscopy, hybrid operating room. Propensity score matching was used to control baseline patient characteristics between traditional and hybrid operating room approaches. There were 144 patients in the traditional group and 157 in the hybrid group. In the hybrid group, 41% (64/157) underwent intraoperative angiograms, and of those, 58% (37/64) received at least 1 endovascular intervention. Following propensity matching, 125 patients remained in each the traditional and hybrid groups. Thirty-day survival was significantly improved in the hybrid cohort at 96.7% (122/125) as compared to the traditional cohort at 87.2% (109/125) (P = 0.002). There were no significant differences in perioperative paralysis (1.6% vs 1.6%, P > 0.9), new hemodialysis (12% vs 9.6%, P = 0.5), fasciotomy (2.4% vs 5.6%, P = 0.20, and exploratory laparotomy (1.6% vs 4.8%, P = 0.3). The hybrid operating room approach to type A aortic dissection, provides the ability to immediately assess distal malperfusion and perform endovascular interventions at the time of open aortic repair, and is associated with significantly higher 30-day and 2-year survival when compared to a stepwise repair approach in a traditional operating room.

Biomechanical engineering analysis of an acute papillary muscle rupture disease model using an innovative 3D-printed left heart simulator.

OBJECTIVES: The severity of acute papillary muscle (PM) rupture varies according to the extent and site of the rupture. However, the haemodynamic effects of different rupture variations are still poorly understood. Using a novel ex vivo model, we sought to study acute PM rupture to improve clinical management. METHODS: Using porcine mitral valves (n = 32) mounted within an ex vivo left heart simulator, PM rupture was simulated. The mitral valve was divided into quadrants for analysis according to the PM heads. Acute PM rupture was simulated by incrementally cutting from 1/3 to the total number of chordae arising from 1 PM head of interest. Haemodynamic parameters were measured. RESULTS: Rupture >2/3 of the chordae from 1 given PM head or regurgitation fraction >60% led to markedly deteriorated haemodynamics. Rupture at the anterolateral PM had a stronger negative effect on haemodynamics than rupture at the posteromedial PM. Rupture occurring at the anterior head of the anterolateral PM led to more marked haemodynamic instability than rupture occurring at the other PM heads. CONCLUSIONS: The haemodynamic effects of acute PM rupture vary considerably according to the site and extent of the rupture. Rupture of ≤2/3 of chordae from 1 PM head or rupture at the posteromedial PM lead to less marked haemodynamics effects, suggesting a higher likelihood of tolerating surgery. Rupture at the anterolateral PM, specifically the anterior head, rupture of >2/3 of chordae from 1 PM head or regurgitation fraction >60% led to marked haemodynamic instability, suggesting the potential benefit from bridging strategies prior to surgery.

Early Discharge After Lobectomy for Lung Cancer Does Not Equate to Early Readmission.

BACKGROUND: Enhanced recovery after surgery pathways in several specialties reduce length of stay, but accelerated discharge after thoracic surgery is not well characterized. This study tested the hypothesis that patients discharged on postoperative day 1 (POD1) after lobectomy for lung cancer have an increased risk of readmission. METHODS: Patients who underwent a lobectomy for lung cancer between 2011 and 2019 in the American College of Surgeons National Surgical Quality Improvement Program database were identified. Readmission rates were compared between patients discharged on postoperative day 1 (POD 1) and patients discharged on POD 2 to 6. Early discharge and readmission predictors were evaluated using multivariable logistic regression analysis. RESULTS: Only 854 (3.8%) of 22,585 patients who met inclusion criteria were discharged on POD 1, although POD 1 discharge rates increased from 2.3% to 8.1% (P < .001) from 2011 to 2019, respectively. Median hospitalization for patients discharged on POD 2 to 6 was 4 days (interquartile range, 3 to 5 days). Patients' characteristics associated with a lower likelihood of POD 1 discharge were increasing age, smoking, or a history of dyspnea, whereas a minimally invasive approach was the strongest predictor of early discharge (adjusted odds ratio, 5.42; P < .001). Readmission rates were not significantly different for the POD 1 and POD 2 to 6 groups in univariate analysis (6.0% vs 7.0%; P = .269). Further, POD 1 discharge was not a risk factor for readmission in multivariable analysis (adjusted odds ratio, 1.10; P = .537). CONCLUSIONS: Select patients can be discharged on POD 1 after lobectomy for lung cancer without an increased readmission risk, a finding supporting this accelerated discharge target inclusion in lobectomy enhanced recovery after surgery protocols.