Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study.

BACKGROUND: Frequent anti-vascular endothelial growth factor A (VEGF-A) injections reduce the risk of rapid and severe vision loss in patients with neovascular age-related macular degeneration (nAMD); however, due to undertreatment, many patients lose vision over time. New treatments that provide sustained suppression of VEGF-A are needed. RGX-314 (currently known as ABBV-RGX-314) is an adeno-associated virus serotype 8 vector that expresses an anti-VEGF-A antigen-binding fragment, which provides potential for continuous VEGF-A suppression after a single subretinal injection. We report results on the safety and efficacy of subretinal injection of RGX-314 in patients with nAMD. METHODS: For this open-label, multiple-cohort, multicentre, phase 1/2a, dose-escalation study conducted at eight sites in the USA, we enrolled participants with nAMD aged 50-89 years who had previously been treated with anti-VEGF injections into five cohorts (with five different doses of RGX-314). To be eligible, participants had to have macular neovascularisation secondary to nAMD with subretinal or intraretinal fluid in the centre subfield, be pseudophakic (after cataract removal), and have a best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400 for the first participant in each cohort and between 20/40 and 20/400 for others. Subretinal injection of RGX-314 was done without a pre-bleb by a wet-laboratory-trained vitreoretinal surgeon. Cohort 1 received 3 × 109 genome copies per eye, cohort 2 received 1 × 1010, and cohort 3 received 6 × 1010. Two additional dose cohorts (cohort 4: 1·6 × 1011; cohort 5: 2·5 × 1011) were added. Participants were seen 1 day and 1 week after administration of RGX-314, and then monthly for 2 years (up to week 106). The primary outcome was safety of RGX-314 delivered by subretinal injection up to week 26. This analysis includes all 42 patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT03066258. FINDINGS: Between May 12, 2017, and May 21, 2019, we screened 110 patients for eligibility and enrolled 68. 42 participants demonstrated the required anatomic response to intravitreal ranibizumab and then received a single RGX-314 injection (dose range 3 × 109 to 2·5 × 1011 genome copies per eye) and were followed up for 2 years. There were 20 serious adverse events in 13 participants, of which one was possibly related to RGX-314: pigmentary changes in the macula with severe vision reduction 12 months after injection of RGX-314 at a dose of 2·5 × 1011 genome copies per eye. Asymptomatic pigmentary changes were seen in the inferior retinal periphery several months after subretinal injection of RGX-314 most commonly at doses of 6 × 1010 genome copies per eye or higher. There were no clinically determined immune responses or inflammation beyond that expected following routine vitrectomy. Doses of 6 × 1010 genome copies or higher resulted in sustained concentrations of RGX-314 protein in aqueous humour and stable or improved BCVA and central retinal thickness with few or no supplemental anti-VEGF-A injections in most participants. INTERPRETATION: Subretinal delivery of RGX-314 was generally well tolerated with no clinically recognised immune responses. RGX-314 gene therapy provides a novel approach for sustained VEGF-A suppression in patients with nAMD that has potential to control exudation, maintain vision, and reduce treatment burden after a single administration. Results from this study informed the pivotal programme to evaluate RGX-314 in patients with nAMD. FUNDING: RegenxBio.

The Adherence to an Intraoperative Blood Product Transfusion Algorithm Is Associated With Reduced Blood Product Transfusions in Cardiac Surgical Patients Undergoing Coronary Artery Bypass Grafts and Aortic and/or Valve Replacement Surgery: A Single-Center, Observational Study.

OBJECTIVE: To demonstrate the value of a viscoelastic-based intraoperative transfusion algorithm to reduce non-RBC product administration in adult cardiac surgical patients. DESIGN: A prospective observational study. SETTING: At a quaternary academic teaching hospital. PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: Viscoelastic-based intraoperative transfusion algorithm. MEASUREMENTS AND MAIN RESULTS: The study authors compared intraoperative blood product transfusion rates in 184 cardiac surgical patients to 236 historic controls after implementing a viscoelastic-based algorithm. The authors found a non-significant reduction in transfusion of 23.8% for fresh frozen plasma (FFP) units (0.84 ± 1.4 v 0.64 ± 1.38; p = ns), 33.4% for platelet units (0.90 ± 1.39 v 0.60 ± 131; p = ns), and 15.8% for cryoprecipitate units (0.19 ± 0.54 v 0.16 ± 0.50; p = ns). They found a 43.9% reduction in red blood cell (RBC) units transfused (1.98 ± 2.24 v 0.55 ± 1.36; p = 0.008). There were no statistically significant differences in time to extubation (8.0 hours (4.0-21.0) v 8.0 (4.0-22.3), reoperation for bleeding (15 [12.3%] v 10 [10.6%]), intensive care unit length of stay (ICU LOS) (51.0 hours [28.0-100.5] v 53.5 [33.3-99.0]) or hospital LOS (9.0 days [6.0-15.0] v 10.0 [7.0-17.0]). Deviation from algorithm adherence was 32.7% (48/147). Packed RBC, FFP, platelets, cryoprecipitate, and cell saver were significantly reduced in the Algorithm Compliant Cohort compared with historic controls, whereas times to extubation, ICU LOS, and hospital LOS did not reach significance. CONCLUSIONS: After the implementation of a viscoelastic-based algorithm, patients received fewer packed RBC, FFP, platelets, cryoprecipitate, and cell saver. Algorithm-compliant patients received fewer transfusions; however, reductions in times to extubation, ICU LOS, and hospital LOS were not statistically significant compared with historic controls.

Persistent malperfusion after central aortic repair in acute type I aortic dissections.

OBJECTIVE: Acute dissection involving the ascending aorta and extending beyond the innominate artery (DeBakey type I) may be associated with acute ischemic complications owing to branch artery malperfusion. The purpose of this study was to document the prevalence of noncardiac ischemic complications associated with type I aortic dissections that persisted after initial ascending aortic and hemiarch repair, necessitating vascular surgery intervention. METHODS: Consecutive patients presenting with acute type I aortic dissections between 2007 and 2022 were studied. Patients who underwent initial ascending aortic and hemiarch repair were included in the analysis. Study end points included the need for additional interventions after ascending aortic repair and death. RESULTS: There were 120 patients (70% men; mean age, 58 ± 13 years) who underwent emergent repair for acute type I aortic dissections during the study period. Forty-one patients (34%) presented with acute ischemic complications. These included 22 (18%) with leg ischemia, 9 (8%) with acute strokes, 5 (4%) with mesenteric ischemia, and 5 (4%) with arm ischemia. After proximal aortic repair, 12 patients (10%) had persistent ischemia. Nine patients (8%) required additional interventions for persistent leg ischemia (n = 7), intestinal gangrene (n = 1), or cerebral edema (craniotomy, n = 1). Three other patients with acute stroke had permanent neurologic deficits. All other ischemic complications resolved after the proximal aortic repair despite mean operative times exceeding 6 hours. Comparing patients with persistent ischemia with those whose symptoms resolved after central aortic repair, there were no differences in demographics, distal extent of dissection, mean operative time for aortic repair, or need for venous-arterial extracorporeal bypass support. Overall, 6 of the 120 patients (5%) suffered perioperative deaths. Hospital deaths occurred in 3 of the 12 patients (25%) with persistent ischemia vs none of 29 patients who had resolution of the ischemia after aortic repair (P = .02). Over a mean follow-up of 51 ± 39 months, no patient required an additional intervention for persistent branch artery occlusion. CONCLUSIONS: One-third of patients with acute type I aortic dissections had associated noncardiac ischemia, prompting a vascular surgery consultation. Limb and mesenteric ischemia most often resolved after the proximal aortic repair and did not require further intervention. No vascular interventions were performed in patients with stroke. Although the presence of acute ischemia at presentation did not increase hospital or 5-year mortality rates, persistent ischemia after central aortic repair seems to be a marker for increased hospital mortality after type I dissections.

The Use of a Viscoelastic-Based Transfusion Algorithm Significantly Reduces Non-red Blood Cell Transfusion in Patients Undergoing Left Ventricular Assist Device Placement or Heart Transplantation: A Single-Center Observational Study.

OBJECTIVES: Does point-of-care viscoelastic testing in patients undergoing left ventricular assist device implantation or orthotopic heart transplantation reduce non-red blood cell transfusion or improve postoperative outcomes? DESIGN: A retrospective observational study. SETTING: At a single-center tertiary university hospital. PARTICIPANTS: Patients undergoing left ventricular assist device placement or heart transplantation INTERVENTIONS: The authors implemented a TEG-based transfusion algorithm to reduce non-red cell transfusion rates compared with historical controls. MEASUREMENTS AND MAIN RESULTS: From May 15, 2019, through March 20, 2020, 68 patients underwent left ventricular assist device placement or heart transplantation. Algorithm adherence was 49.2%. After adjusting for relevant variables, platelet (odds ratio [OR] 0.58 [0.39-0.84]; p = 0.004) and cryoprecipitate (OR 0.37 [0.19-0.72]; p = 0.004) transfusion rates and time to extubation (OR -14.1 [-25.8 to -2.3]; p = 0.020) were significantly reduced compared with historical controls. After adjusting for relevant clinical variables, there was a statistically significant reduction in plasma (median [interquartile range] 0.16 [0.07-0.36], p < 0.001), platelets (0.06 [0.02-0.21], p < 0.001), and cryoprecipitate (0.06 [0.01-0.47], p = 0.007) transfusion rates and time to extubation (-16.95 [-27.20 to -6.71], p = 0.002) compared with historical controls. CONCLUSIONS: The authors report a statistically significant reduction in transfusion of platelets and cryoprecipitate and time to extubation after adjusting for relevant clinical variables compared with historical controls and a significant reduction in the transfusion of plasma, platelets, and cryoprecipitate and time to extubation in those patients for whom the transfusion algorithm was followed. Their results suggest the importance of implementing transfusion algorithms for patients undergoing heart transplantation and left ventricular assist device placement and of accounting for adherence.

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.

Prolonged extracorporeal preservation and evaluation of human lungs with portable normothermic ex vivo perfusion.

Many lung donor offers are refused despite increasing demand. Portable normothermic ex vivo lung perfusion (EVLP) could increase donor yield by monitoring and reconditioning extended criteria donor (ECD) lungs. We report its use in human lungs declined for clinical transplantation. Ten sets of such lungs were procured from brain-dead donors and underwent 24 hours of normothermic EVLP using a perfusate based on donor whole blood. Hemodynamic and ventilatory data and P:F ratios were measured. Advanced donor age and borderline oxygenation (donor mean P:F 228 ± 73) were the most commonly cited reasons for refusal for transplantation. There was no significant worsening of pulmonary hemodynamics or compliance or significant P:F decline during preservation in the overall cohort. Mean P:F ratio in the overall cohort was 315 ± 88 mm Hg after 24 hours EVLP. At EVLP termination 5/10 lung blocks met standard EVLP thresholds for acceptability for transplant. Eventual EVLP performance was poorly predicted by donor P:F ratio but well predicted by data gathered early in EVLP. Portable normothermic EVLP is useful for transportation, monitoring, and reconditioning of ECD lungs. Early EVLP measurements are more effective than preprocurement donor P:F in predicting eventual allograft performance. We advocate an aggressive strategy of evaluation of ECD lungs using blood-based EVLP.

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.

Disparity among Asian Americans in transcatheter and surgical aortic valve replacement.

BACKGROUND: Racial disparities in transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) outcomes have been established, but research has predominantly focused on African Americans and Hispanics, leaving a gap in Asian Americans. This study aimed to investigate disparities in aortic valve replacement outcomes among Asian Americans. METHODS: Patients who underwent SAVR and TAVR were identified in National Inpatient Sample from the last quarter of 2015-2020. A 1:2 propensity score matching was applied to Asian Americans and Caucasians. In-hospital perioperative outcomes, length of stay, days from admission to operation, and total hospital charge, were compared. RESULTS: In TAVR, 51,394 (84.41 %) were Caucasians and 795 (1.31 %) were Asian Americans. In SAVR, there were 50,080 (78.52 %) Caucasians and 1233 (1.93 %) Asian Americans. No significant difference was found in post-TAVR complications. However, Asian Americans experienced longer waiting time until operation (p = 0.03) and higher costs (p < 0.01) in TAVR. In SAVR, Asian Americans had higher risks of in-hospital mortality (3.91 % vs 2.39 %, p = 0.01), cardiogenic shock (8.71 % vs 6.74 %, p = 0.03), respiratory complications (14.08 % vs 11.2 %, p = 0.01), mechanical ventilation (13.83 % vs 9.09 %, p < 0.01), acute kidney injury (25.47 % vs 20.13 %, p < 0.01), and hemorrhage/hematoma (72.01 % vs 62.95 %, p < 0.01). Additionally, Asian Americans underwent SAVR had longer lengths of stay (p < 0.01) and higher costs (p < 0.01). CONCLUSIONS: Asian Americans were underrepresented in aortic valve replacement. Asian Americans, while having similar post-TAVR outcomes to Caucasians, faced greater risks of post-SAVR mortality and surgical complications. These disparities among Asian Americans call for targeted actions to ensure equitable health outcomes.

Weekend Admission is Associated with Higher Kidney Failures after Thoracic Endovascular Aneurysm Repair for Stanford Type B Aortic Dissection.

BACKGROUND: Weekend effect characterized by worse perioperative outcomes has been demonstrated in some surgery patients admitted on weekends, as opposed to weekdays. This study aimed to examine weekend effect on open surgical repair or thoracic endovascular aneurysm repair (TEVAR) for Stanford Type B Aortic Dissection (TBAD). METHODS: Patients who underwent TBAD repair were identified in National/Nationwisde Inpatient Sample from Q4 2015-2020. Open surgery and TEVAR were examined separately. Multivariable analyses were performed comparing in-hospital perioperative outcomes of patients under weekday and weekend admission. Adjusted preoperative variables included sex, age, race, socioeconomic status, hospital characteristics, clinical symptoms, comorbidities, and elective/non-elective admission. Also, length of stay, days from admission to operation, and total hospital charge were compared. RESULTS: Among patients who underwent open TBAD repair, 1321 were admitted on weekdays and 340 on weekends. Among patients who underwent TEVAR for TBAD, 2018 were admitted on weekdays and 440 wereadmitted on weekends. There was no difference in open repair outcomes between those admitted on weekdays vs weekends. In TEVAR, weekend admission was associated with higher post-procedural kidney failure (1.14% vs .20%, aOR = 4.11, P = .04) and superficial wound complications (2.73% vs 1.49%, aOR = 2.2, P = .03) but lower respiratory complications (5.80% vs 3.64%, aOR = .47, P = .01). Also, in TEVAR, weekend admission was associated with longer time from admission to operation (3.92 ± .27 vs 2.35 ± .09 days, P < .01). CONCLUSIONS: Renal malperfusion was a common indication for TBAD repair. TBAD patients admitted over the weekend and underwent TEVAR had higher post-procedural kidney failure, which may be due to delayed diagnosis and treatment.

Smaller Hospital Size is Associated With Higher Mortality in Stanford Type A Aortic Dissection.

BACKGROUND: Stanford Type A Aortic Dissection (TAAD) is associated with high in-hospital mortality and the need for immediate surgical intervention. Larger hospital size may be associated with better patient care and surgical outcomes. This study aimed to examine the effect of hospital size on TAAD outcomes. METHOD: Patients who underwent TAAD repair were identified in National Inpatient Sample (NIS) from Q4 2015-2020. NIS stratifies hospital size into small, medium, and large based on the number of hospital beds, geographical location, and the teaching status of the hospitals. Patients admitted to small/medium and large hospitals were stratified into two cohorts. Multivariable logistic regressions were performed to compare in-hospital outcomes, adjusted for demographics, comorbidity, primary payer status, and hospital characteristics including procedural volume. RESULTS: There were 1106 and 3752 TAAD admitted to small/medium and large hospitals, respectively. Among patients admitted to small/medium hospitals, there was higher mortality (17.27% vs 14.37%, aOR = 1.32, P < 0.01), but shorter length of stay (P < 0.01) and lower cost (P = 0.03) compared to larger hospitals. There was no difference in morbidities. CONCLUSIONS: Marked higher mortality is associated with admission to smaller hospitals among patients with TAAD, which may in turn decrease the average hospital stay and cost. Given that a significant percentage of patients are already being transferred out of the initial hospital and small/medium hospital is associated with higher mortality, centralization of care in centers of excellence may decrease the high mortality associated with TAAD.

Does previous valve replacement affect short-term coronary artery bypass grafting outcomes? A population-based National Inpatient Sample study from 2015 to 2020.

BACKGROUND: Coronary artery disease (CAD) and valvular disease frequently coexist due to similar pathophysiology. Effort has been dedicated to comprehending the outcomes of concomitant coronary revascularization and valve replacement procedures. However, the understanding of how prior valve replacement affects the outcomes of coronary artery bypass grafting (CABG) remains limited. Thus, this study aimed to conduct a population-based examination of the in-hospital outcomes in patients with previous valve replacement in CABG. METHODS: Patients who underwent CABG were identified in the National Inpatient Sample in the USA from Q4 2015-2020. Patients with age < 18 years and concomitant procedures were excluded. A 1:3 propensity-score matching was used to address differences in demographics, socioeconomic status, primary payer status, hospital characteristics, comorbidities, and transfer/admission status between patients with and without previous valve replacement. In-hospital postoperative outcomes were assessed. RESULTS: There were 514 patients with previous valve replacement who underwent CABG, who were matched to 1588 out of 167,668 controls. After matching, patients with valve replacement had mostly comparable in-hospital outcomes except for a higher risk of vascular complications (1.75 % vs 0.57 %, p = 0.02), a longer length of stay (10.90 ±â€¯7.04 days vs 9.95 ±â€¯6.53 days, p = 0.01), and higher hospital charges (275,465 ±â€¯229,088 US dollars vs 231,648 ±â€¯189,938 US dollars, p < 0.01). CONCLUSION: For short-term outcomes, CABG is generally safe for patients who have undergone previous valve replacement, although there is an increased risk of vascular complications that may warrant additional attention. The findings of this study can be valuable for preoperative risk assessment of patients who have had valve replacement and are considering CABG.

African Americans have worse outcomes after transcatheter and surgical aortic valve replacement: A national inpatient sample analysis from 2015 to 2020.

BACKGROUND: Racial disparities in transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) are controversial among African Americans (AA). This study investigated racial disparities comparing AA and Caucasians undergoing aortic valve replacement. METHODS: Patients who underwent SAVR and TAVR for aortic stenosis were identified in National Inpatient Sample from Q4 2015-2020. In-hospital perioperative outcomes, length of stay, days from admission to operation, and total hospital charge, were compared between AA and Caucasians using multivariable analysis, adjusting for sex, age, socioeconomic status, comorbidity, and hospital characteristics. RESULTS: In TAVR, 51,394 (84.41 %) were Caucasians and 2433 (4.00 %) were AA. In SAVR, there were 50,080 (78.52 %) Caucasians and 3565 (5.59 %) AA. Compared to Caucasians, AA underwent TAVR had a higher risk of complications such as major adverse cardiovascular events (MACE) [adjusted odds ratio (aOR) = 1.335, p = 0.02)], respiratory complications (aOR = 1.363, p = 0.01), acute kidney injury (AKI) (aOR = 1.468, p < 0.01), pulmonary embolism (aOR = 4.65, p = 0.05), hemorrhage/hematoma (aOR = 1.202, p < 0.01), or superficial wound complication (aOR = 1.414, p = 0.04). AA who underwent SAVR had higher risks of morality (aOR = 1.184, p < 0.05) and surgical complications including MACE (aOR = 1.263, p < 0.01), pericardial complications (aOR = 1.563, p < 0.01), cardiogenic shock (aOR = 1.578, p < 0.01), respiratory complications (aOR = 1.261, p < 0.01), AKI (aOR = 1.642, p < 0.01), venous thromboembolism (aOR = 1.613, p < 0.01), hemorrhage/hematoma (aOR = 1.129, p < 0.01), infection (aOR = 1.234, p < 0.01), superficial wound complications (aOR = 1.756, p < 0.01), vascular complications (aOR = 1.592, p < 0.01), and diaphragmatic paralysis (aOR = 2.181, p = 0.02). In both TAVR and SAVR, AA had longer waiting times from admission to operation (p < 0.01), longer hospital stays (p < 0.01), and higher hospital charges (p < 0.01). CONCLUSION: AA were underrepresented, especially in TAVR. AA experienced higher in-hospital mortality post-SAVR, but not after TAVR. Furthermore, AA had more complications for both TAVR and SAVR. These findings underscore the pronounced disparities among AA in aortic valve replacement.

Patients with metastatic cancer have worse short-term coronary artery bypass grafting outcomes: A population-based study of National Inpatient Sample from 2015 to 2020.

BACKGROUND: Metastasis is a hallmark for cancer progression. While patients with metastatic cancer (MC) have higher risk profiles, outcomes of coronary artery bypass grafting (CABG) in these patients have not been established, likely due to their smaller representation in the CABG patient population. This study aimed to examine the short-term outcomes of patients with MC who underwent CABG. METHODS: Patients who underwent CABG were identified in National Inpatient Sample from Q4 2015-2020. Exclusion criteria included age <18 years, concomitant procedures, and non-metastatic malignancies. A 1:3 propensity-score matching was used to address differences in demographics, socioeconomic status, primary payer status, hospital characteristics, comorbidities, and transfer/admission status between MC and non-MCC patients. In-hospital post-CABG outcomes were evaluated. RESULTS: There were 379 (0.23 %) patients with MC who underwent CABG. All MC patients were matched to 1161 out of 164,351 non-MC patients who underwent CABG during the same period. Patients with MC had higher risks of mortality (4.76 % vs 2.58 %, p = 0.04), pacemaker implantation (2.91 % vs 1.12 %, p = 0.03), venous thromboembolism (1.85 % vs 0.43 %, p = 0.01), and hemorrhage/hematoma (61.11 % vs 55.04 %, p = 0.04). In addition, MC patients had a longer time from admission to operation (3.35 ± 4.19 vs 2.82 ± 3.54 days, p = 0.03) and longer hospital length of stay (11.86 ± 8.17 vs 10.65 ± 8.08 days, p = 0.01). CONCLUSION: Patients with MC had higher short-term mortality and morbidities after CABG. These findings can help provide insights for clinicians in the management of patients with concurrent coronary artery disease and MC, particularly in terms of preoperative risk stratification and therapeutic decision-making.

In-hospital outcome of type A aortic dissection repair in patients with chronic obstructive pulmonary disease: A population study of National Inpatient Sample from 2015 to 2020.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common comorbidity that has been linked to higher mortality and respiratory complications in cardiac surgery. However, the postoperative outcomes for COPD patients undergoing Type A Aortic Dissection (TAAD) repair remain unexplored. Thus, this study aimed to assess the impact of COPD on in-hospital outcomes of TAAD repair in a national registry. METHODS: Patients undergoing TAAD repair were identified in National Inpatient Sample from the last quarter of 2015-2020. Multivariable logistic regressions were used to compare in-hospital outcomes between patients with and without COPD, where demographics, comorbidities, hospital characteristics, primary payer status, and transfer status were adjusted. RESULTS: There were 701 (16.37 %) COPD patients and 3581 (83.63 %) non-COPD patients who went under TAAD repair, where the prevalence of COPD was higher than in the general population (6 %). COPD and non-COPD patients have comparable rates of in-hospital mortality (14.69 % vs 15.19 %, aOR 1.016, 95 CI 0.797-1.295, p = 0.9) and there was no indication of delayed surgery. However, COPD patients had a higher risk of mechanical ventilation (37.80 % vs 31.42 %, aOR 1.521, 95 CI 1.267-1.825, p < 0.01) and a higher rate of transferring out to other facilities (38.37 % vs 32.23 %, aOR 1.271, 95 CI 1.054-1.533, p = 0.01). In addition, COPD patients had a longer hospital length of stay (14.28 ± 11.32 vs 13.85 ± 12.78 days, F = 5.61, p = 0.01). CONCLUSION: The presence of COPD could be a risk factor for the development of aortic dissection. However, outcomes for COPD patients were largely similar to those without COPD. These findings can be valuable for preoperative assessments and tailoring perioperative care for COPD patients undergoing TAAD repair.

Impact of lung transplantation on diastolic dysfunction in recipients with pretransplant pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension can cause left ventricular diastolic dysfunction through ventricular interdependence. Moreover, diastolic dysfunction has been linked to adverse outcomes after lung transplant. The impact of lung transplant on diastolic dysfunction in recipients with pretransplant pulmonary hypertension is not defined. In this cohort, we aimed to assess the prevalence of diastolic dysfunction, the change in diastolic dysfunction after lung transplant, and the impact of diastolic dysfunction on lung transplant outcomes. METHODS: In a large, single-center database from January 2011 to September 2021, single or bilateral lung transplant recipients with pulmonary hypertension (mean pulmonary artery pressure > 20 mm Hg) were retrospectively identified. Those without a pre- or post-transplant echocardiogram within 1 year were excluded. Diastolic dysfunction was diagnosed and graded according to the American Society of Echocardiography 2016 guideline on assessment of diastolic dysfunction (present, absent, indeterminate). McNemar's test was used to examine association between diastolic dysfunction pre- and post-transplant. Kaplan-Meier and Cox regression analysis were used to assess associations between pre-lung transplant diastolic dysfunction and post-lung transplant 1-year outcomes, including mortality, major adverse cardiac events, and bronchiolitis obliterans syndrome grade 1 or higher-free survival. RESULTS: Of 476 primary lung transplant recipients, 205 with pulmonary hypertension formed the study cohort (mean age, 56.6 ± 11.9 years, men 61.5%, mean pulmonary artery pressure 30.5 ± 9.8 mm Hg, left ventricular ejection fraction < 55% 9 [4.3%]). Pretransplant, diastolic dysfunction was present in 93 patients (45.4%) (grade I = 8, II = 84, III = 1), absent in 16 patients (7.8%), and indeterminate in 89 patients (43.4%), and 7 patients (3.4%) had missing data. Post-transplant, diastolic dysfunction was present in 7 patients (3.4%) (grade I = 2, II = 5, III = 0), absent in 164 patients (80.0%), and indeterminate in 15 patients (7.3%), and 19 patients (9.3%) had missing data. For those with diastolic dysfunction grades in both time periods (n = 180), there was a significant decrease in diastolic dysfunction post-transplant (148/169 patients with resolved diastolic dysfunction; McNemar's test P < .001). Pretransplant diastolic dysfunction was not associated with major adverse cardiac events (hazard ratio [HR], 1.08, 95% CI, 0.72-1.62; P = .71), bronchiolitis obliterans syndrome-free survival (HR, 0.67, 95% CI, 0.39-1.56; P = .15), or mortality (HR, 0.70, 95% CI, 0.33-1.46; P = .34) at 1 year. CONCLUSIONS: Diastolic dysfunction is highly prevalent in lung transplant candidates with normal left ventricular systolic function and pulmonary hypertension, and resolves in most patients after lung transplant regardless of patient characteristics. Pre-lung transplant diastolic dysfunction was not associated with adverse lung or cardiac outcomes after lung transplant. Collectively, these findings suggest that the presence of diastolic dysfunction in lung transplant recipients with pulmonary hypertension has no prognostic significance, and as such diastolic dysfunction and the associated clinical syndrome of heart failure with preserved ejection fraction should not be considered a relative contraindication to lung transplant in such patients.

Development of Comorbidity Index for in-hospital mortality for patients who underwent coronary artery revascularization.

BACKGROUND: For myocardial revascularization, coronary artery bypass grafting (CAGB) and percutaneous coronary intervention (PCI) are two common modalities but with high in-hospital mortality. A Comorbidity Index is useful to predict mortality or can be used with other covariates to develop point-scoring systems. This study aimed to develop specific comorbidity indices for patients who underwent coronary artery revascularization. METHODS: Patients who underwent CABG or PCI were identified in the National Inpatient Sample database between Q4 2015-2020. Patients of age <40 were excluded for congenital heart defects. Patients were randomly sampled into experimental (70%) and validation (30%) groups. Thirty-eight Elixhauser comorbidities were identified and included in multivariable regression to discriminate in-hospital mortality. Weight for each comorbidity was assigned and single indices, Li CABG Mortality Index (LCMI) and Li PCI Mortality Index (LPMI), were developed. RESULTS: Mortality discrimination by LCMI approached adequacy (c-statistic=0.691, 95% CI=0.682-0.701) and was comparable to multivariable regression with comorbidities (c-statistic=0.685, 95% CI=0.675-0.694). LCMI discrimination performed significantly better than Elixhauser Comorbidity Index (ECI) (c-statistic=0.621, 95% CI=0.611-0.631) and can be further improved by adjusting age (c-statistic=0.721, 95% CI=0.712-0.730). All models were well-calibrated (Brier score=0.021-0.022). LPMI moderately discriminated in-hospital mortality (c-statistic=0.666, 95% CI=0.660-0.672) and performed significantly better than ECI (c-statistic=0.610, 95% CI=0.604-0.616). LPMI performed better than the all-comorbidity multivariable regression (c-statistic=0.658, 95% CI=0.652-0.663). After age adjustment, LPMI discrimination was significantly increased and was approaching adequacy (c-statistic=0.695, 95% CI=0.690-0.701). All models were well-calibrated (Brier score=0.025-0.026). CONCLUSIONS: LCMI and LPMI effectively discriminated and predicted in-hospital mortality. These indices were validated and performed superior to ECI. These indices can standardize comorbidity measurement as alternatives to ECI to help replicate and compare results across studies.

Posterolateral thoracotomy: unique approach to tricuspid valve replacement after right pneumonectomy.

A 72-year-old patient presented with severe tricuspid regurgitation and patent foramen ovale (PFO) in the setting of severe mediastinal shifting after remote right pneumonectomy. Surgical approach was challenging given the significant herniation of the heart and left lung into the right hemithorax. This report describes tricuspid valve replacement with PFO closure via a right posterolateral thoracotomy and alternative cardiopulmonary bypass cannulation strategy.

Smoker's paradox in transcatheter aortic valve replacement: A National Inpatient Sample analysis from 2015 to 2020.

BACKGROUND: While smoking is recognized as a risk factor for multiple cardiovascular conditions, prior research has identified a smoker paradox, wherein smokers had better post-procedural outcomes following transcatheter aortic valve replacement (TAVR) in the initial years of its introduction among high-risk patients only. In recent years, TAVR has expanded to significant larger groups of low-risk patients and became the dominate approach for aortic valve replacement. Consequently, the study cohort from the previous research can no longer represent the current patient populations undergoing TAVR. This study aimed to examine the impact of smoking on TAVR outcomes in the later post-TAVR era. METHODS: Patients who underwent TAVR were identified in the National Inpatient Sample (NIS) database from the last quarter of 2015-2020 by ICD-10-PCS. Patients were stratified into two cohorts based on smoker status. Multivariable analysis was performed comparing in-hospital post-TAVR outcomes. Adjusted pre-procedural variables included sex, age, race, socioeconomic status, comorbidities, and hospital characteristics. RESULTS: A total number of 58,934 patients who underwent TAVR were identified including 23,683 smokers and 35,251 non-smokers. Compared to non-smokers, smokers had lower in-hospital mortality (aOR 0.589, p < 0.01), MACE (aOR 0.678, p < 0.01), MI (aOR 0.719, p < 0.01), stroke (aOR 0.599, p < 0.01), neurological complications (aOR 0.653, p < 0.01), pacemaker implantation (aOR 0.911, p < 0.01), cardiogenic shock (aOR 0.762, p < 0.01), respiratory complications (aOR 0.822, p < 0.01), mechanical ventilation (aOR 0.669, p < 0.01), AKI (aOR 0.745, p < 0.01), VTE (aOR 0.578, p < 0.01), hemorrhage/hematoma (aOR 0.921, p < 0.01), infection (aOR 0.625, p < 0.01), vascular complications (aOR 0.802, p < 0.01), reopen surgery (aOR 0.453), and transfer out to another facility (aOR 0.79, p < 0.01). In addition, cigarette smokers had shorter LOS (p < 0.01), and less hospital charge (p < 0.01). CONCLUSION: This study identified the smoker paradox in the later post-TAVR era with remarkably broad protection from many complications and lower mortality. The reasons underlying this apparent smoker paradox merit deeper investigation.

New-onset postoperative atrial fibrillation after mitral valve surgery: Determinants and the effect on survival.

Objective: Mitral valve surgery (MVS) carries substantial risk of postoperative atrial fibrillation (PAF). Identifying patients who benefit from prophylactic left atrial appendage amputation (LAAA) or maze is ill-defined. To guide such interventions, we determined preoperative predictors of PAF and investigated 3-year survival of patients with PAF. Methods: We performed a retrospective analysis of patients undergoing isolated MVS (N = 670) between 2011 and 2021. Patients with preoperative atrial fibrillation, LAAA or pulmonary vein isolation were excluded. Patient characteristics were compared between those without PAF and those who developed transient or prolonged PAF. Predictors of any PAF and prolonged PAF were identified using multivariable regression analysis. Results: In total, 504 patients without preoperative atrial fibrillation underwent isolated MVS. Of them, 303 patients (60.2%) developed PAF; 138 (27.3%) developed transient and 165 (32.7%) developed prolonged (beyond 30 days) PAF. Patients with PAF were older (65.7 vs 54.3 years, P < .001), with larger left atria (4.8 vs 4.3 cm, P < .001), greater prevalence of hypertension (60% vs 47.8%, P < .05), and were New York Heart Association class III/IV (36% vs 8.5%, P < .001). Independent predictors of PAF included left atria volume index (odds ratio [OR], 1.02; P < .003), older age (OR, 1.04; P < .001), heart failure (OR, 6.73; P < .001), and sternotomy (OR, 2.19; P < .002). Age, heart failure, and sternotomy were independent predictors of prolonged PAF. Patients with PAF had greater mortality at 3 years compared with those without PAF (5.3% vs 0.5%, P < .005). On multivariable analysis, PAF was associated with increased mortality (hazard ratio, 7.81; P < .046). Conclusions: PAF is common after MVS and associated with late mortality. Older age, advanced heart failure, and sternotomy are associated with prolonged PAF. These factors may identify patients who would benefit from prophylactic LAAA or ablation during MVS.