Deep learning for transesophageal echocardiography view classification.

Transesophageal echocardiography (TEE) imaging is a vital tool used in the evaluation of complex cardiac pathology and the management of cardiac surgery patients. A key limitation to the application of deep learning strategies to intraoperative and intraprocedural TEE data is the complexity and unstructured nature of these images. In the present study, we developed a deep learning-based, multi-category TEE view classification model that can be used to add structure to intraoperative and intraprocedural TEE imaging data. More specifically, we trained a convolutional neural network (CNN) to predict standardized TEE views using labeled intraoperative and intraprocedural TEE videos from Cedars-Sinai Medical Center (CSMC). We externally validated our model on intraoperative TEE videos from Stanford University Medical Center (SUMC). Accuracy of our model was high across all labeled views. The highest performance was achieved for the Trans-Gastric Left Ventricular Short Axis View (area under the receiver operating curve [AUC] = 0.971 at CSMC, 0.957 at SUMC), the Mid-Esophageal Long Axis View (AUC = 0.954 at CSMC, 0.905 at SUMC), the Mid-Esophageal Aortic Valve Short Axis View (AUC = 0.946 at CSMC, 0.898 at SUMC), and the Mid-Esophageal 4-Chamber View (AUC = 0.939 at CSMC, 0.902 at SUMC). Ultimately, we demonstrate that our deep learning model can accurately classify standardized TEE views, which will facilitate further downstream deep learning analyses for intraoperative and intraprocedural TEE imaging.

Racial Disparities in Failure to Rescue after Pediatric Heart Surgeries in the US.

OBJECTIVE: To identify the trend in failure to rescue (FTR) and risk factors contributing to racial disparities in FTR after pediatric heart surgery using contemporary nationwide data. STUDY DESIGN: We identified 85 267 congenital heart surgeries in patients <18 years of age from 2009 to 2019 using the Kid's Inpatient Database. The primary outcome was FTR. A mixed-effect logistic regression model with hospital random intercept was used to identify independent predictors of FTR. RESULTS: Among 36 753 surgeries with postoperative complications, the FTR was 7.3%. The FTR decreased from 7.4% in 2009 to 6.3% in 2019 (P = .02). FTR was higher among Black than White children for all years. The FTR was higher among girls (7.2%) vs boys (6.6%), children aged <1 (9.6%) vs 12-17 years (2.4%), and those of Black (8.5%) vs White race (5.9%) (all P < .05). Black race was associated with a higher FTR odds (OR, 1.40; 95% CI, 1.20-1.65) after adjusting for demographics, medical complexity, nonelective admission, and hospital surgical volume. Higher hospital volume was associated with a lower odds of FTR for all racial groups, but fewer Black (19.7%) vs White (31%) children underwent surgery at high surgical volume hospitals (P < .001). If Black children were operated on in the same hospitals as White children, the racial differences in FTR would decrease by 47.3%. CONCLUSIONS: Racial disparities exist in FTR after pediatric heart surgery in the US. The racial differences in the location of care may account for almost half the disparities in FTR.

Bicuspid aortic stenosis: National three-year outcomes of transcatheter versus surgical aortic valve replacement among Medicare beneficiaries.

OBJECTIVE: Randomized trials of transcatheter versus surgical aortic valve replacements have excluded bicuspid anatomy. We compared 3-year outcomes of transcatheter aortic valve replacement versus surgical aortic valve replacement in patients aged more than 65 years with bicuspid aortic stenosis. METHODS: The Centers for Medicare and Medicaid data were used to identify 6450 patients undergoing isolated surgical aortic valve replacement (n = 3771) or transcatheter aortic valve replacement (n = 2679) for bicuspid aortic stenosis (2012-2019). Propensity score matching with 21 baseline characteristics including frailty created 797 pairs. RESULTS: Unmatched patients undergoing transcatheter aortic valve replacement were older than patients undergoing surgical aortic valve replacement (78 vs 70 years), with more comorbidities and frailty (all P < .001). After matching, transcatheter aortic valve replacement was associated with a similar mortality risk compared with surgical aortic valve replacement within the first 6 months (hazard ratio [HR], 1.08, 95% CI, 0.67-1.69) but a higher mortality risk between 6 months and 3 years (HR, 2.16, 95% CI, 1.22-3.83). Additionally, transcatheter aortic valve replacement was associated with a lower risk of heart failure readmissions before 6 months (HR, 0.51, 95% CI, 0.31-0.87) but a higher risk between 6 months and 3 years (HR, 4.78, 95% CI, 2.21-10.36). The 3-year risks of aortic valve reintervention (HR, 1.03, 95% CI, 0.30-3.56) and stroke (HR, 1.21, 95% CI, 0.75-1.96) were similar. CONCLUSIONS: Among matched Medicare beneficiaries undergoing transcatheter aortic valve replacement or surgical aortic valve replacement for bicuspid aortic stenosis, 3-year mortality was higher after transcatheter aortic valve replacement. However, transcatheter aortic valve replacement was associated with a similar risk of mortality and a lower risk of heart failure readmissions during the first 6 months after the intervention. Randomized comparative data are needed to best inform treatment choice.

Socioeconomic disparities in midterm outcomes after repair for degenerative mitral regurgitation.

OBJECTIVE: The influence of socioeconomic disparities on survival after mitral repair is poorly defined. We examined the association between socioeconomic disadvantage and midterm outcomes of repair in Medicare beneficiaries with degenerative mitral regurgitation. METHODS: US Centers for Medicare and Medicaid Services data were used to identify 10,322 patients undergoing isolated first-time repair for degenerative mitral regurgitation between 2012 and 2019. Zip code-level socioeconomic disadvantage was dichotomized with the Distressed Communities Index, which incorporates education level, poverty, unemployment, housing security, median income, and business growth; those with Distressed Communities Index score ≥80 were classified as distressed. The primary outcome was survival, censored at 3 years. Secondary outcomes included cumulative incidences of heart failure readmission, mitral reintervention, and stroke. RESULTS: Of the 10,322 patients undergoing degenerative mitral repair, 9.7% (n = 1003) came from distressed communities. Patients from distressed communities underwent surgery at lower volume centers (11 vs 16 cases/year) and traveled further for surgical care (40 vs 17 miles) (both P values < .001). At 3 years, unadjusted survival (85.4%; 95% CI, 82.9%-87.5% vs 89.7%; 95% CI, 89.0%-90.4%) and cumulative incidence of heart failure readmission (11.5%; 95% CI, 9.6%-13.7% vs 7.4%; 95% CI, 6.9%-8.0%) were worse in patients from distressed communities (all P values < .001), whereas mitral reintervention rates were similar (2.7%; 95% CI, 1.8%-4.0% vs 2.8%; 95% CI, 2.5%-3.2%; P = .75). After adjustment, community distress was independently associated with 3-year mortality (hazard ratio, 1.21; 95% CI, 1.01-1.46) and heart failure readmissions (hazard ratio, 1.28; 95% CI, 1.04-1.58). CONCLUSIONS: Community-level socioeconomic distress is associated with worse outcomes in degenerative mitral repair among Medicare beneficiaries.

Left atrial appendage closure during mitral repair in patients without atrial fibrillation.

OBJECTIVE: Routine left atrial appendage closure during mitral repair in patients without atrial fibrillation (AF) is controversial. We aimed to compare the incidence of stroke after mitral repair in patients without recent AF according to left atrial appendage closure. METHODS: An institutional registry identified 764 consecutive patients without recent AF, endocarditis, prior appendage closure, or stroke undergoing isolated robotic mitral repair between 2005 and 2020. Left atrial appendages were closed via left atriotomy using a double-layer continuous suture in 5.3% (15 out of 284) patients before 2014, versus 86.7% (416 out of 480) after 2014. The cumulative incidence of stroke (including transient ischemic attack) was determined using statewide hospital data. Median follow-up was 4.5 years (range, 0-16.6 years). RESULTS: Patients undergoing left atrial appendage closure were older (63 vs 57.5 years, P < .001), with higher prevalence of remote AF requiring cryomaze (9%, n = 40 vs 1%, n = 3, P < .001). After appendage closure there were fewer reoperations for bleeding (0.7% [n = 3] vs 3% [n = 10]; P = .02), and more AF (31.8% [n = 137] vs 25.2% [n = 84]; P = .047). Two-year freedom from >2+ mitral regurgitation was 97%. Six strokes and 1 transient ischemic attack occurred after appendage closure compared with 14 and 5 in patients without (P = .002), associated with a significant difference in 8-year cumulative incidence of stroke/transient ischemic attack (hazard ratio, 0.3; 95% CI, 0.14-0.85; P = .02). This difference persisted in the sensitivity analysis, excluding patients undergoing concomitant cryomaze procedures. CONCLUSIONS: Routine left atrial appendage closure during mitral repair in patients without recent AF appears safe and was associated with a lower risk of subsequent stroke/transient ischemic attack.

Bridging with surgically placed microaxial left ventricular assist devices: a high-volume centre experience.

OBJECTIVES: The Impella 5.0 and 5.5 have largely superseded non-ambulatory temporary mechanical support devices; yet, clinical outcomes are predominantly limited to small series: this study presents the experience of a high-volume centre. METHODS: An institutional clinical registry was used to identify all patients with cardiogenic shock who underwent Impella 5.0 or 5.5 implantation from January 2014 to March 2022. The primary outcome was survival to device explantation. RESULTS: The study cohort comprised 221 patients, including 146 (66.1%) Impella 5.0 and 75 (33.9%) Impella 5.5 patients. The primary aetiology was non-ischaemic cardiomyopathy (50.7%, n = 112), ischaemic cardiomyopathy (23.1%, n = 51) and acute myocardial infarction (26.2%, n = 58). Patients were prospectively classified according to strategy as bridge to transplant (47.5%, n = 105), bridge to durable device (13.6%, n = 30) or bridge to recovery (38.9%, n = 86). Patients were predominantly Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2 (95.0%, n = 210). The median bridging duration was 14 (range 0-137) days. Device exchange, Ischaemic stroke and ipsilateral arm ischaemia occurred in 8.1% (n = 18), 2.7% (n = 6) and 1.8% (n = 4) of patients, respectively. Compared to the 75 most recent Impella 5.0 patients, Impella 5.5 patients (n = 75) had lower rates of device exchange (4.0%, n = 3 vs 13.3%, n = 10, P = 0.04). Overall, 70.1% (n = 155) of patients survived to Impella explantation. CONCLUSIONS: The Impella 5.0 and 5.5 provide safe and effective temporary mechanical support in appropriately selected patients with cardiogenic shock. The newer device generation may have a lower requirement for device exchange as compared to its predecessor.

Heart transplantation for COVID-19 myopathy in the United States.

Evidence on characteristics and outcomes of patients undergoing heart transplantation for coronavirus disease 2019 (COVID-19) associated cardiomyopathy is limited to case reports. Of all 6,332 patients aged ≥18 years undergoing heart transplantation from July 2020 through May 2022 in the United Network for Organ Sharing database, 12 (0.2%) patients had COVID-19 myocarditis and 98 (1.6%) patients with the same level of care had non-COVID-19 myocarditis. Their median age was 49 (range 19-74) years. All patients were hospitalized in the intensive care unit and 92.7% (n = 102) were on life support prior to transplantation. No patients with COVID-19 myocarditis required ventilation while waitlisted. Survival free from graft failure was 100% among COVID-19 patients and 88.5% among non-COVID-19 patients at a median of 257 (range 0-427) days post-transplant. These findings indicate that transplantation is rarely performed for COVID-19 related cardiomyopathy in the United States, yet early outcomes appear favorable in select patients.

Isolated Tricuspid Operations: The Society of Thoracic Surgeons Adult Cardiac Surgery Database Analysis.

BACKGROUND: Population-level data are limited regarding contemporary practice and outcomes of isolated tricuspid operations. We evaluated this using The Society of Thoracic Surgeons Adult Cardiac Surgery Database. METHODS: We identified 14,704 isolated tricuspid operations from The Society of Thoracic Surgeons Adult Cardiac Surgery Database from July 1, 2011 to June 30, 2020. After excluding patients with endocarditis, tricuspid stenosis, emergent/emergent salvage status, previous heart transplants, and missing tricuspid operation type, 6507 patients remained. Endpoints were operative mortality and composite major comorbidities (permanent stroke, renal failure, prolonged ventilation > 24 hours, deep sternal wound infection, cardiac reoperations, and new permanent pacemaker implantation). RESULTS: Isolated tricuspid operations increased from 2012 (983 cases) to 2019 (2155 cases, P < .001). Median annual center volume was 2 cases (range, 1-81). In the final cohort (n = 6507; median age, 65 years; 38.5% men), 40% had New York Heart Association class III/IV heart failure and 24% had nonelective operations. The operative mortality was 7.3% (1.7% in patients without these risk factors), and new permanent pacemaker implant rate was 10.8%. In the multivariable analysis, factors associated with operative mortality included New York Heart Association class III/IV heart failure (odds ratio [OR], 1.57), nonelective operations (OR, 1.91), tricuspid replacement (OR, 1.56), annual center volume ≤ 5 cases (OR, 1.37), and higher model for end-stage liver disease scores (all P < .05). Beating heart operation was associated with a lower adjusted risk of pacemaker implant (OR, 0.69), renal failure (OR, 0.75), and blood transfusions (OR, 0.8) compared with full cardioplegic arrest (all P < .05). CONCLUSIONS: Isolated tricuspid repair was associated with lower adjusted mortality and morbidities than replacement. Beating heart operation was associated with lower adjusted major morbidities. The preoperative model for end-stage liver disease scores may identify high-risk patients, and early referral to higher volume centers may help improve outcomes.

Heart transplantation using donation after circulatory death in the United States.

OBJECTIVES: Heart donation after circulatory death was recently reintroduced in the United States with hopes of increasing donor heart availability. We examined its national use and outcomes. METHODS: The United Network for Organ Sharing database was used to identify validated adult patients undergoing heart transplantation using donation after circulatory death donors (n = 266) and donation after brain death donors (n = 5998) between December 1, 2019, and December 31, 2021, after excluding heart-lung transplants. Propensity score matching was used to create more balanced groups for comparison. RESULTS: The monthly percentage of donation after circulatory death heart transplant increased from 2.5% in December 2019 to 6.8% in December 2021 (P < .001). Twenty-two centers performed donation after circulatory death heart transplants, ranging from 1 to 75 transplants per center. Four centers performed 70% of the national volume. Recipients of donation after circulatory death hearts were more likely to be clinically stable (80.4% vs 41.1% in status 3-6, P < .001), to have type O blood (58.3% vs 39.9%, P < .001), and to wait longer after listing (55, interquartile range, 15-180 days vs 32, interquartile range, 9-160 days, P = .003). Six-month survival was 92.1% (95% confidence interval, 91.3-92.8) after donation after brain death heart transplants and 92.6% (95% confidence interval, 88.1-95.4) after donation after circulatory death heart transplants (hazard ratio, 0.94, 95% confidence interval, 0.57-1.54, P = .79). Outcomes in propensity-matched patients were similar except for higher rates of treated acute rejection in donation after circulatory death transplants before discharge (14.4% vs 8.8%, P = .01). In donation after circulatory death heart recipients, outcomes did not differ based on the procurement technique (normothermic regional perfusion vs direct procurement and perfusion). CONCLUSIONS: Heart transplantation with donation after circulatory death donors has short-term survival comparable to donation after brain death transplants. Broader implementation could substantially increase donor organ availability.

Ross Procedure in Children: The Society of Thoracic Surgeons Congenital Heart Surgery Database Analysis.

BACKGROUND: Single-center studies have demonstrated excellent results for the Ross procedure in children. We aimed to evaluate national variation in clinical outcomes using The Society of Thoracic Surgeons Congenital Heart Surgery Database. METHODS: The database was used to identify 2805 children undergoing the Ross procedure from 2000 through 2018, comprising 163 neonates (<30 days, 5.8%), 448 infants (30-365 days, 16.0%), 1444 children (1-12 years, 51.5%), and 750 teenagers (13-17 years, 26.7%). Centers were divided into terciles by procedural volume. Multivariable logistic regression was used to identify predictors of a composite outcome of operative mortality, neurologic deficit, or renal failure requiring dialysis. RESULTS: Neonates and infants were more likely to present with aortic stenosis than children and teenagers (61.7% [n = 377] vs 34.6% [n = 760]; P < .01) and have risk factors including preoperative shock (9.2% [n = 56] vs 0.4% [n = 8]; P < .01). Operative mortality was 24.1% (n = 39) in neonates, 11.2% (n = 50) in infants, 1.5% (n = 21) in children , and 0.8% (n = 6) in teenagers (P < .01). Independent predictors of the composite outcome in children aged <1 year included neonatal age (odds ratio [OR], 3.0; 95% CI, 1.9-4.8), low-volume center (OR, 2.1; 95% CI, 1.1-3.9), and procedure year (OR, 0.7; 95% CI, 0.5-0.9 per 5 years). In children aged ≥1 year, no association was found between center volume, procedure year, and outcome. CONCLUSIONS: The Ross procedure is being performed with low mortality in children aged ≥1 year throughout North America. High-volume centers have improved outcomes in children aged <1 year, who have different anatomic characteristics and risk profiles.

Sex Disparities in Failure to Rescue After Cardiac Surgery in California and New York.

BACKGROUND: Women have a higher risk of mortality than men after cardiac surgery independent of other risk factors. The reason for this may not be limited to patient-specific variables. Failure to rescue (FTR) patients from death after a postoperative complication is a nationally endorsed quality care metric. We aimed to identify whether sex disparities exist in the quality of care after cardiac surgery using FTR rates. METHODS: A retrospective analysis of 30 973 men (70.4%) and 13 033 women (29.6%) aged over 18 years undergoing coronary artery bypass graft or valve surgery in New York (2016-2019) and California (2016-2018) who experienced at least one serious postoperative complication. The primary outcome was the FTR. Multivariable logistic regression was used to identify predictors of death after complication. Propensity matching was used to adjust for baseline differences between sexes and yielded 12 657 pairs. RESULTS: Female patients that experienced complications were older (mean age 67.8 versus 66.7, P<0.001), more frail (median frailty score 0.1 versus 0.07, P<0.001), and had more comorbidities (median Charlson score 2.5 versus 2.3, P<0.001) than male patients. The overall FTR rate was 5.7% (2524), men were less likely to die after a complication than women (4.8% versus 8%, P<0.001). Independent predictors of FTR included female sex (relative risk [RR]: 1.46 [CI, 1.30-1.62]), area-level poverty rate >20% (RR, 1.21 [CI, 1.01-1.59]), higher frailty (RR, 2.83 [CI, 1.35-5.93]), undergoing concomitant coronary artery bypass graft and valve surgeries (RR, 1.69 [CI, 1.49-1.9]), and higher number of postoperative complications (RR, 16.28 [CI, 14-18.89]). In the propensity-matched cohorts, the FTR rate remained significantly lower among men than women (6.0% versus 8.0%, P<0.001). CONCLUSIONS: Women are less likely to be rescued from death following postoperative complications, independent of socioeconomic and clinical characteristics. Further research is warranted to investigate the clinical practices contributing to this disparity in quality of care following cardiac surgery.

Robotic degenerative mitral repair: Factors associated with intraoperative revision and impact of mild residual regurgitation.

OBJECTIVES: National registry data show wide variability in degenerative mitral repair rates and infrequent use of intraoperative repair revision to eliminate residual mitral regurgitation (MR). The consequence of uncorrected mild residual MR is also not clear. We identified factors associated with intraoperative revision of degenerative mitral repair and evaluated long-term effects of intraoperative mild residual MR. METHODS: A prospective institutional registry of 858 patients with degenerative MR undergoing robotic mitral surgery was linked to statewide databases. Univariate logistic regression identified factors associated with intraoperative repair revision. Survival was estimated using the Kaplan-Meier method and adjusted with Cox regression. Late freedom from more-than-moderate MR or reintervention was estimated with death as a competing risk. RESULTS: Repair rate was 99.3%. Repair was revised intraoperatively in 19 patients and was associated with anterior or bileaflet prolapse, adjunctive repair techniques, and annuloplasty band size (all P < .05). Intraoperative repair revision did not result in increased postoperative complications. Intraoperative mild residual MR (n = 111) was independently associated with inferior 8-year survival (hazard ratio, 2.97; 95% CI, 1.33-6.23), worse freedom from more than moderate MR (hazard ratio, 3.35; 95% CI, 1.60-7.00), and worse freedom from mitral reintervention (hazard ratio, 6.40; 95% CI, 2.19-18.72) (all P < .01). CONCLUSIONS: A near 100% repair rate with acceptable durability may be achieved safely with intraoperative revision of postrepair residual MR. Mild residual MR was independently associated with reduced survival, worse freedom from more-than-moderate MR, and worse freedom from mitral reintervention at 8-year follow-up.

Radio-Frequency Manipulation of State Populations in an Entangled Fluorine-Muon-Fluorine System.

Entangled spin states are created by implanting muons into single-crystal LiY_{0.95}Ho_{0.05}F_{4} to form a cluster of correlated, dipole-coupled local magnetic moments. The resulting states have well-defined energy levels allowing experimental manipulation of the state populations by electromagnetic excitation. Experimental control of the evolution of the muon spin polarization is demonstrated through application of continuous, radio-frequency electromagnetic excitation fields. A semiclassical model of quantum, dipole-coupled spins interacting with a classical, oscillating magnetic field accounts for the muon spin evolution. On application of the excitation field, this model shows how changes in the state populations lead to the experimentally observed effects, thus enabling a spectroscopic probe of entangled spin states with muons.

Robotic repair for Barlow mitral regurgitation: Repairability, safety, and durability.

OBJECTIVE: In Barlow disease, increased repair complexity drives decreased repair rates. We evaluated outcomes of a simplified approach to robotic mitral repair in Barlow disease. METHODS: A prospective institutional registry with vital-statistics, statewide admissions and echocardiographic follow-up was used to identify 924 consecutive patients undergoing robotic surgery for degenerative mitral regurgitation (MR) between 2005 and 2020, including 12% (n = 111) with Barlow disease. Freedom from >moderate (>2+) MR was analyzed with death as a competing risk and predictors of failure were analyzed using multivariable Cox regression. Median follow-up was 5.5 years (range, 0-15 years). RESULTS: Patients with Barlow disease were younger (median, age 59 years; interquartile range [IQR], 51-67 vs 62; IQR, 54-70 years, P = .05) than patients without Barlow disease. Replacements were performed in 0.9% (n = 1) of patients with Barlow disease and 0.8% (n = 6) of patients without Barlow disease (P = 1). Repairs comprised simple leaflet resection and annuloplasty band in 73.9% (n = 546) of non-Barlow valves versus 12.7% (n = 14) of patients with Barlow disease who required neochordae (53.6%, n = 59), chordal transfer (20%, n = 22), and commissural sutures (37.3%, n = 41), with longer cardiopulmonary bypass time (median 133; IQR, 117-149 minutes vs 119; IQR, 106-142 minutes, P < .01). Survival free from greater than moderate MR at 5 years was 92.0% (95% confidence interval [CI], 80.2%-98.1%) in patients with Barlow disease versus 96.0% (95% CI, 93.3%-98.0%) in patients without Barlow disease (P = .40). Predictors of late failure included Barlow disease (hazard ratio, 3.9; 95% CI, 1.7-9.0) and non-Barlow isolated anterior leaflet prolapse (hazard ratio, 5.6; 95% CI, 2.3-13.4). CONCLUSIONS: Barlow disease may be reliably and safely repaired with acceptable long-term durability by experienced robotic mitral surgery programs.

Durable Robotic Mitral Repair of Degenerative Primary Regurgitation With Long-Term Follow-Up.

BACKGROUND: Variation in degenerative mitral morphology may contribute to suboptimal repair rates. This study evaluates outcomes of a standardized mitral repair technique. METHODS: An institutional clinical registry was used to identify 1036 consecutive patients undergoing robotic mitral surgery between 2005 and 2020: 87% (n = 902) had degenerative disease. Calcification, failed transcatheter repair, and endocarditis were excluded, leaving 582 (68%) patients with isolated posterior leaflet and 268 (32%) with anterior or bileaflet prolapse. Standardized repair comprised triangular resection and true-sized flexible band in posterior leaflet prolapse. Freedom from greater than 2+ moderate mitral regurgitation stratified by prolapse location was assessed using competing risk analysis with death as a competing event. Median follow-up was 5.5 (range 0-15) years. RESULTS: Of patients with isolated posterior leaflet prolapse, 87% (n = 506) had standardized repairs and 13% (n = 76) had additional or nonresectional techniques vs 24% (n = 65) and 76% (n = 203), respectively, for anterior or bileaflet prolapse (P < .001). Adjunctive techniques in the isolated posterior leaflet group included chordal reconstruction (8.6%, n = 50) and commissural sutures (3.4%, n = 20). Overall, median clamp time was 80 (interquartile range, 68-98) minutes, 17 patients required intraoperative re-repair, and 6 required mitral replacement. Freedom from greater than 2+ regurgitation or reintervention at 10 years was 92% for posterior prolapse (vs 83% for anterior or bileaflet prolapse). Anterior or bileaflet prolapse was associated with late greater than 2+ regurgitation (hazard ratio, 3.0; 95% confidence interval, 1.3-7.0). CONCLUSIONS: Posterior leaflet prolapse may be repaired in greater than 99% of patients using triangular resection and band annuloplasty, with satisfactory long-term durability. Increased risk of complex repairs and inferior durability highlights the value of identifying anterior and bileaflet prolapse preoperatively.

Robotic Mitral Valve Repair After Failed Transcatheter Edge-to-Edge Repair.

Mitral valve repair is infrequently performed in patients undergoing corrective surgery for failed mitral transcatheter edge-to-edge repair in current United States practice. This article describes surgical techniques for reconstructive surgery after failed transcatheter edge-to-edge repair. Nine patients underwent robotic-assisted mitral surgery after failed transcatheter edge-to-edge repair between 2008 and 2020 at a single center. Repair was completed in 88.9% (n = 8) patients, and freedom from >2+ mitral regurgitation was 87.5% (n = 7) at a median follow-up of 1.9 years.

Mitral Surgery After Transcatheter Edge-to-Edge Repair: Society of Thoracic Surgeons Database Analysis.

BACKGROUND: Transcatheter edge-to-edge (TEER) mitral repair may be complicated by residual or recurrent mitral regurgitation. An increasing need for surgical reintervention has been reported, but operative outcomes are ill defined. OBJECTIVES: This study evaluated national outcomes of mitral surgery after TEER. METHODS: The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database was used to identify 524 adults who underwent mitral surgery after TEER between July 2014 and June 2020. Emergencies (5.0%; n = 26), previous mitral surgery (5.3%; n = 28), or open implantation of transcatheter prostheses (1.5%; n = 8) were excluded. The primary outcome was 30-day or in-hospital mortality. RESULTS: In the study cohort of 463 patients, the median age was 76 years (interquartile range [IQR]: 67 to 81 years), median left ventricular ejection fraction was 57% (IQR: 48% to 62%), and 177 (38.2%) patients had degenerative disease. Major concomitant cardiac surgery was performed in 137 (29.4%) patients: in patients undergoing isolated mitral surgery, the median STS-predicted mortality was 6.5% (IQR: 3.9% to 10.5%), the observed mortality was 10.2% (n = 23 of 225), and the ratio of observed to expected mortality was 1.2 (95% confidence interval [CI]: 0.8 to 1.9). Predictors of mortality included urgent surgery (odds ratio [OR]: 2.4; 95% CI: 1.3 to 4.6), nondegenerative/unknown etiology (OR: 2.2; 95% CI: 1.1 to 4.5), creatinine of >2.0 mg/dl (OR: 3.8; 95% CI: 1.9 to 7.9) and age of >80 years (OR: 2.1; 95% CI: 1.1 to 4.4). In a volume outcomes analysis in an expanded cohort of 591 patients at 227 hospitals, operative mortality was 2.6% (n = 2 of 76) in 4 centers that performed >10 cases versus 12.4% (n = 64 of 515) in centers performing fewer (p = 0.01). The surgical repair rate after failed TEER was 4.8% (n = 22) and was 6.8% (n = 12) in degenerative disease. CONCLUSIONS: This study indicates that mitral repair is infrequently achieved after failed TEER, which may have implications for treatment choice in lower-risk and younger patients with degenerative disease. These findings should inform patient consent for TEER, clinical trial design, and clinical performance measures.

Oncolytic reovirus in combination with chemotherapy in metastatic or recurrent non-small cell lung cancer patients with KRAS-activated tumors.

BACKGROUND: The type 3 Dearing reovirus (Reolysin) is a naturally occurring virus that preferentially infects and causes oncolysis in tumor cells with a Ras-activated pathway. It induces host immunity and cell cycle arrest and acts synergistically with cytotoxic agents. METHODS: This study evaluated Reolysin combined with paclitaxel and carboplatin in patients with metastatic/recurrent KRAS-mutated or epidermal growth factor receptor (EGFR)-mutated/amplified non-small cell lung cancer. RESULTS: Thirty-seven patients were treated. Molecular alterations included 20 KRAS mutations, 10 EGFR amplifications, 3 EGFR mutations, and 4 BRAF-V600E mutations. In total, 242 cycles (median, 4; range, 1-47) were completed. The initial doses were area under the curve (AUC) 6 mg/mL/min for carboplatin, 200 mg/m(2) for paclitaxel on day 1, and 3 × 10(10) 50% tissue culture infective dose for Reolysin on days 1 to 5 of each 21-day cycle. Because of diarrhea and febrile neutropenia (in the first 2 patients), subsequent doses were reduced to 175 mg/m(2) for paclitaxel and AUC 5 mg/mL/min for carboplatin. Toxicities included fatigue, diarrhea, nausea/vomiting, neutropenia, arthralgia/myalgia, anorexia, and electrolyte abnormalities. Response Evaluation Criteria in Solid Tumors 1.0 responses included the following: partial response for 11 patients, stable disease (SD) for 20 patients, progressive disease for 4 patients, and not evaluable for 2 patients (objective response rate, 31%; 90% 1-sided lower confidence interval, 21%). Four SD patients had >40% positron emission tomography standardized uptake value reductions. The median progression-free survival, median overall survival, and 12-month overall survival rate were 4 months, 13.1 months, and 57%, respectively. Seven patients were alive after a median follow-up of 34.2 months; they included 2 patients without disease progression at 37 and 50 months. CONCLUSIONS: Reolysin in combination with paclitaxel and carboplatin was well tolerated. The observed response rate suggests a benefit of the reovirus for chemotherapy. A follow-up randomized study is recommended. The proportion of patients surviving longer than 2 years (30%) suggests a second/third-line treatment effect or possibly the triggering of an immune response after tumor reovirus infiltration.

The combination of intravenous Reolysin and gemcitabine induces reovirus replication and endoplasmic reticular stress in a patient with KRAS-activated pancreatic cancer.

BACKGROUND: Activating mutations in RAS are present in the majority of pancreatic cancer cases and represent an ideal therapeutic target. Reolysin is a proprietary formulation of oncolytic reovirus that is currently being evaluated in multiple clinical trials due to its ability to selectively replicate in cells harboring an activated RAS pathway. Here we report for the first time the presence of reovirus replication and induction of endoplasmic reticular (ER) stress in a primary tumor specimen collected from a pancreatic cancer patient receiving intravenous Reolysin and gemcitabine. CASE PRESENTATION: We describe the case of a 54-year old patient diagnosed with pancreatic adenocarcinoma in February 2012. Analysis of a tumor biopsy revealed an activating KRAS mutation (G12D) and the patient was started on first-line treatment with Reolysin in combination with gemcitabine in March 2012. Stable disease was achieved with significant improvement in cancer-related pain. Following 25 cycles of treatment over 23 months, a second biopsy was collected and immunohistochemical analyses revealed the presence of reovirus replication and induction of the ER stress-related gene GRP78/BIP and the pro-apoptotic protein NOXA. Importantly, co-localization of reoviral protein and active caspase-3 was also observed in the biopsy specimen. CONCLUSION: This is the first report of reoviral protein detection in primary tumor biopsies taken from a pancreatic cancer patient receiving intravenous Reolysin therapy. The accumulation of reoviral protein was associated with ER stress induction and caspase-3 processing suggesting that Reolysin and gemcitabine treatment exhibited direct pro-apoptotic activity against the tumor.

Phase I trial of cyclophosphamide as an immune modulator for optimizing oncolytic reovirus delivery to solid tumors.

PURPOSE: Reovirus is a wild-type oncolytic virus that is ubiquitous in the environment; most patients are therefore preimmune. Therapeutic administration leads to an increase in neutralizing antireovirus antibody (NARA) titer. We hypothesized that if NARA limited reovirus antitumor activity, the effect might be attenuated by coadministration of cyclophosphamide. EXPERIMENTAL DESIGN: In a phase I study, patients with advanced cancer received cyclophosphamide 3 days before intravenous reovirus serotype 3 Dearing (RT3D). The primary objective was to reduce the resulting rise in NARA titer. Cyclophosphamide dose was escalated from 25-1,000 mg/m(2) through nine cohorts; we aimed to define a well-tolerated immunomodulatory dose. RESULTS: The combination was well tolerated in 36 patients, with grade 3/4 toxicities only seen at or above the maximum tolerated dose of cyclophosphamide, which was 800 mg/m(2) combined with reovirus. Immunosuppressive effect, defined as maintaining NARA titer rise below a predefined threshold, was observed in only one patient. Furthermore, despite expected myelosuppression seen at higher cyclophosphamide doses, no changes in T-cell subsets, including Tregs, occurred with dose escalation. Viable virus was detected in association with peripheral blood mononuclear cells (PBMC) from 14% of patients 10 days after the last RT3D injection, despite high plasma NARA titer, demonstrating a potential mechanism for prolonged evasion of neutralization by reovirus. CONCLUSIONS: Coadministration of cyclophosphamide with reovirus is safe, but does not attenuate host antiviral responses. Alternative immunomodulation approaches should be explored, but association with PBMCs may allow reovirus to persist and evade even high levels of neutralizing antibodies.