Uncommon presentations of type A quadricuspid aortic valve in the Septuagenarian.

BACKGROUND: Quadricuspid aortic valve (QAV) is a rare congenital anomaly characterized by the presence of four cusps instead of the usual three. It is estimated to occur in less than 0.05% of the population, with Type A (four equal-sized leaflets) accounting for roughly 30% of QAV subtypes. Based on limited clinical series, the usual presentation is progressive aortic valve regurgitation (AR) with symptoms occurring in the fourth to sixth decade of life. Severe aortic valve stenosis (AS) and acute AR are very uncommon. CASE PRESENTATION: We describe two cases of Type A QAV in patients who remained asymptomatic until their seventies with very uncommon presentations: one with severe AS and one with acute, severe AR and flail leaflet. In Case A, a 72-year-old patient with history of moderate AS presents to clinic with progressive exertional dyspnea. During work-up for transcatheter vs. surgical replacement pre-operative computed tomography angiogram (CTA) reveals a quadricuspid aortic valve with severe AS, and the patient undergoes surgical aortic valve replacement. Pre-discharge transthoracic echocardiography (TTE) shows good prosthetic valve function with no gradient or regurgitation. In Case B, a 76-year-old patient is intubated upon arrival to the hospital for acute desaturation, found to have wide open AR on catheterization, and transferred for emergent intervention. Intraoperative TEE reveals QAV with flail leaflet and severe AR. Repair is considered but deferred ultimately due to emergent nature. Post-operative TTE demonstrates good prosthetic valve function with no regurgitation and normal biventricular function. CONCLUSIONS: QAV can present as progressive severe AS and acute AR, with symptoms first occurring in the seventh decade of life. The optimal treatment for QAV remains uncertain. Although aortic valve repair or transcatheter option may be feasible in some patients, aortic valve replacement remains a tenable option.

A Systematic Review of the Recruitment and Outcome Reporting by Sex and Race/Ethnicity in Stent Device Development Trials for Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: Women and racial/ethnic minority groups have been shown to experience poor outcomes after endovascular aortic aneurysm repair (EVAR). One potential reason is the rare inclusion of these populations in initial phases of device development. The objective of this systematic review is to understand enrollment and outcome reporting by sex and race/ethnicity in industry-funded EVAR device development trials. METHODS: MEDLINE, PubMed, and Embase were searched from inception to January 2022 without language restrictions using the following terminology: "stent", "graft", "endograft", "device", and "abdominal aortic aneurysm" (AAA). CLINICALTRIALS: gov was also searched from inception to January 2022 for "AAA." Two independent reviewers screened and extracted data. All phase I-III and postmarket evaluation trials that included patients ≥18 years of age, who underwent EVAR were assessed. Participation-to-prevalence ratios (PPRs) were calculated to estimate representation of participants by sex and race/ethnicity in trials compared with their share of disease burden. RESULTS: Among the 4,780 retrieved articles, 55 industry-funded trials met inclusion criteria for this review. A total of 51 trials (93%) reported enrollment by sex/gender, and only 7 trials (13%) reported enrollment by race/ethnicity of the participants. A median of 19 (interquartile range [IQR]: 4.5, 51) women participants were recruited compared to 171 (IQR: 57, 311.5) men, and 17 (IQR: 7.5, 21.5) racial/minority patients were recruited compared to 241 (IQR: 123, 463.5) White participants. Women represent 16.6% of the disease population, and the median PPR is 0.62 (IQR: 0.42, 0.88), which has remained constant over time (Figure 1). None of the device trials reported outcomes based on sex/gender or race/ethnicity. CONCLUSIONS: This systematic review highlights the disparities in recruitment and outcome reporting based on sex and race/ethnicity in EVAR device development trials. While most trials may be underpowered to study these differences, recent registry studies show differential outcomes based on sex and race/ethnicity of vascular patients. Therefore, it is imperative to include and report outcomes in these participants, starting from the initial device development phases to improve generalizability of device-use and understand sources of variation in device performance.

Rationale and design of a mechanistic clinical trial of JAK inhibition to prevent ventilator-induced diaphragm dysfunction.

INTRODUCTION: Ventilator-induced diaphragm dysfunction (VIDD) is an important phenomenon that has been repeatedly demonstrated in experimental and clinical models of mechanical ventilation. Even a few hours of MV initiates signaling cascades that result in, first, reduced specific force, and later, atrophy of diaphragm muscle fibers. This severe, progressive weakness of the critical ventilatory muscle results in increased duration of MV and thus increased MV-associated complications/deaths. A drug that could prevent VIDD would likely have a major positive impact on intensive care unit outcomes. We identified the JAK/STAT pathway as important in VIDD and then demonstrated that JAK inhibition prevents VIDD in rats. We subsequently developed a clinical model of VIDD demonstrating reduced contractile force of isolated diaphragm fibers harvested after ∼7 vs ∼1 h of MV during a thoracic surgical procedure. MATERIALS AND METHODS: The NIH-funded clinical trial that has been initiated is a prospective, placebo controlled trial: subjects undergoing esophagectomy are randomized to receive 6 preoperative doses of the FDA-approved JAK inhibitor Tofacitinib (commonly used for rheumatoid arthritis) vs. placebo. The primary outcome variable will be the difference in the reduction that occurs in force generation of diaphragm single muscle fibers (normalized to their cross-sectional area), in the Tofacitinib vs. placebo subjects, over 6 h of MV. DISCUSSION: This trial represents a first-in-human, mechanistic clinical trial of a drug to prevent VIDD. It will provide proof-of-concept in human subjects whether JAK inhibition prevents clinical VIDD, and if successful, will support an ICU-based clinical trial that would determine whether JAK inhibition impacts clinical outcome variables such as duration of MV and mortality.

Creation and Global Deployment of a Mobile, Application-Based Cognitive Simulator for Cardiac Surgical Procedures.

Several modern learning frameworks (eg, cognitive apprenticeship, anchored instruction, and situated cognition) posit the utility of nontraditional methods for effective experiential learning. Thus, development of novel educational tools emphasizing the cognitive framework of operative sequences may be of benefit to surgical trainees. We propose the development and global deployment of an effective, mobile cognitive cardiac surgical simulator. In methods, 16 preclinical medical students were assessed. Overall, 4 separate surgical modules (sternotomy, cannulation, decannulation, and sternal closure) were created utilizing the Touch Surgery (London, UK) platform. Modules were made available to download free of charge for use on mobile devices. Usage data were collected over a 6-month period. Educational efficacy of the modules was evaluated by randomizing a cohort of medical students to either module usage or traditional, reading-based self-study, followed by a multiple-choice learning assessment tool. In results, downloads of the simulator achieved global penetrance, with highest usage in the USA, Brazil, Italy, UK, and India. Overall, 5368 unique users conducted a total of 1971 hours of simulation. Evaluation of the medical student cohort revealed significantly higher assessment scores in those randomized to module use versus traditional reading (75% ± 9% vs 61% ± 7%, respectively; P < 0.05). In conclusion, this study represents the first effort to create a mobile, interactive cognitive simulator for cardiac surgery. Simulators of this type may be effective for the training and assessment of surgical students. We investigated whether an interactive, mobile-computing-based cognitive task simulator for cardiac surgery could be developed, deployed, and validated. Our findings suggest that such simulators may be a useful learning tool.

Inheriting the Learner's View: A Google Glass-Based Wearable Computing Platform for Improving Surgical Trainee Performance.

BACKGROUND: It is speculated that, in operative environments, real-time visualization of the trainee's viewpoint by the instructor may improve performance and teaching efficacy. We hypothesized that introduction of a wearable surgical visualization system allowing the instructor to visualize otherwise "blind" areas in the operative field could improve trainee performance in a simulated operative setting. METHODS: A total of 11 surgery residents (4 in general surgery training and 7 in an integrated 6-year cardiothoracic surgery program) participated in the study. Google (Mountain View, CA) Glass hardware running proprietary software from CrowdOptic (San Francisco, CA) was utilized for creation of the wearable surgical visualization system. Both the learner and trainer wore the system, and video was streamed from the learner's system in real time to the trainer, who directed the learner to place needles in a simulated operative field. Subjects placed a total of 5 needles in each of 4 quadrants. A composite error score was calculated based on the accuracy of needle placement in relation to the intended needle trajectories as described by the trainer. Time to task completion (TTC) was also measured and participants completed an exit questionnaire. RESULTS: All residents completed the protocol tasks and the survey. Introduction of the wearable surgical visualization system did not affect mean time to task completion (278 ± 50 vs. 282 ± 69 seconds, p = NS). However, mean composite error score fell significantly once the wearable system was deployed (18 ± 5 vs. 15 ± 4, p < 0.05), demonstrating improved accuracy of needle placement. Most of the participants deemed the device unobtrusive, easy to operate, and useful for communication and instruction. CONCLUSIONS: This study suggests that wearable surgical visualization systems allowing for adoption of the learner's perspective may be a useful educational adjunct in the training of surgeons. Further evaluations of the efficacy of wearable technology in the operating room environment are warranted.

Health status after transcatheter aortic valve replacement in patients at extreme surgical risk: results from the CoreValve U.S. trial.

OBJECTIVES: The purpose of this study was to characterize health status outcomes after transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis among patients at extreme surgical risk and to identify pre-procedural patient characteristics associated with a poor outcome. BACKGROUND: For many patients considering TAVR, improvement in quality of life may be of even greater importance than prolonged survival. METHODS: Patients with severe, symptomatic aortic stenosis who were considered to be at prohibitive risk for surgical aortic valve replacement were enrolled in the single-arm CoreValve U.S. Extreme Risk Study. Health status was assessed at baseline and at 1, 6, and 12 months after TAVR using the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Short Form-12, and the EuroQol-5D. The overall summary scale of the KCCQ (range 0 to 100; higher scores = better health) was the primary health status outcome. A poor outcome after TAVR was defined as death, a KCCQ overall summary score (OS) <45, or a decline in KCCQ-OS of 10 points at 6-month follow-up. RESULTS: A total of 471 patients underwent TAVR via the transfemoral approach, of whom 436 (93%) completed the baseline health status survey. All health status measures demonstrated considerable impairment at baseline. After TAVR, there was substantial improvement in both disease-specific and generic health status measures, with an increase in the KCCQ-OS of 23.9 points (95% confidence interval [CI]: 20.3 to 27.5 points) at 1 month, 27.4 points (95% CI: 24.2 to 30.6 points) at 6 months, 27.4 points (95% CI: 24.1 to 30.8 points) at 12 months, along with substantial increases in Short Form-12 scores and EuroQol-5D utilities (all p < 0.003 compared with baseline). Nonetheless, 39% of patients had a poor outcome after TAVR. Baseline factors independently associated with poor outcome included wheelchair dependency, lower mean aortic valve gradient, prior coronary artery bypass grafting, oxygen dependency, very high predicted mortality with surgical aortic valve replacement, and low serum albumin. CONCLUSIONS: Among patients with severe aortic stenosis, TAVR with a self-expanding bioprosthesis resulted in substantial improvements in both disease-specific and generic health-related quality of life, but there remained a large minority of patients who died or had very poor quality of life despite TAVR. Predictive models based on a combination of clinical factors as well as disability and frailty may provide insight into the optimal patient population for whom TAVR is beneficial. (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902).

Individual differences in field independence influence the ability to determine accurate needle angles.

OBJECTIVE: "Field dependence" is used in cognitive psychology to describe an individual's tendency to be visually distracted by the surrounding environment. Notwithstanding the role of field dependence in contexts in which spatial judgment is important, such as piloting an aircraft, to date, studies linking field dependence to surgical skills have been limited. We evaluated whether field dependence correlates with an ability to anticipate appropriate needle angles in a simulated setting. METHODS: Trainees underwent field dependence testing and then participated in a surgical skills exercise. Correlations between field dependence and surgical skill were computed. Specifically, cardiothoracic surgery residents (n=11) took a battery of cognitive examinations to assess general reasoning and visuospatial judgment. Two written tests, the Rod and Frame test and the Judgment of Line Orientation test, measured the degree of field dependence. The subjects then underwent surgical skills testing. Using a standard needle driver, the participants placed curved needles into a cylindrical silicone mitral valve model with 10 premarked needle entry and exit sites. The components assessed included the ability to load a needle on driver at the appropriate angle. RESULTS: The test results showed a parametric distribution, with internal cognitive testing controls demonstrating valid testing techniques and methods. Performance on the cognitive tests measuring spatial judgment and field dependence correlated significantly with skill at determining the appropriate needle angle load in an inverse fashion (Judgment of Line Orientation test, r=0.61, P<.05; Rod and Frame test, r=-0.52, P=.05), suggesting that residents who were not distracted by surrounding objects performed better. Performance on the cognitive examinations did not correlate with resident training level. CONCLUSIONS: Although our study was of a small cohort, the findings suggest that individuals described as field independent (not easily distracted by external visual cues) might possess improved ability to determine appropriate needle angle loads compared with field-dependent individuals. Additional studies examining the role field dependence might play in the acquisition and execution of surgical tasks are warranted.

Establishment of a transcatheter aortic valve program and heart valve team at a Veterans Affairs facility.

BACKGROUND: The US Food and Drug Administration recently approved a transcatheter aortic valve for patients for whom open heart surgery is prohibitively risky. METHODS: A multidisciplinary heart valve team partnered with administration to launch a transcatheter aortic valve replacement (TAVR) program. Clinical registries were used to show robust valve caseloads and outcomes at our Veterans Affairs (VA) facility and to project future volumes. A TAVR business plan was approved by the VA leadership as part of a multiphase project to upgrade and expand our surgical facilities. RESULTS: The heart valve team completed a training program that included simulations and visits to established TAVR centers. Patients were evaluated and screened through a streamlined process, and the program was initiated successfully. CONCLUSIONS: Establishing a TAVR program at a VA facility requires a multidisciplinary team with experience in heart valve and endovascular therapies and a supportive administration willing to invest in a sophisticated infrastructure.

Simulation and skills training in mitral valve surgery.

OBJECTIVE: Limited exposure and visualization and technical complexity have affected resident training in mitral valve surgery. We propose simulation-based learning to improve skill acquisition in mitral valve surgery. METHODS: After reviewing instructional video recordings of mitral annuloplasty in porcine and plastic models, 11 residents (6 integrated and 5 traditional) performed porcine model mitral annuloplasty. Video-recorded performance was reviewed by attending surgeon providing audio formative feedback superimposed on video recordings; recordings were returned to residents for review. After 3-week practice with plastic model, residents repeated porcine model mitral annuloplasty. Performance assessments initially (prefeedback) and at 3 weeks (postfeedback) were based on review of video recordings on 5-point rating scale (5, good; 3, average; 1, poor) of 11 components. Ratings were averaged for composite score. RESULTS: Time to completion improved from mean 31 ± 9 minutes to 25 ± 6 minutes after 3-week practice (P = .03). At 3 weeks, improvement in technical components was achieved by all residents, with prefeedback scores varying from 2.4 ± 0.6 for needle angles to 3.0 ± 0.5 for depth of bites and postfeedback scores of 3.1 ± 0.8 for tissue handling to 3.6 ± 0.8 for suture management and tension (P ≤ .001). Interrater reliability was greater than 0.8. In this sample, composite scores of first-year integrated and traditional residents were lower than those of senior level residents; comparatively, third-year integrated residents demonstrated good technical proficiency. CONCLUSIONS: Simulation-based learning with formative feedback results in overall improved performance of simulated mitral annuloplasty. In complex surgical procedures, simulation may provide necessary early graduated training and practice. Importantly, a "passing" grade can be established for proficiency-based advancement.

Improvement in coronary anastomosis with cardiac surgery simulation.

OBJECTIVE: Cardiac surgery trainees might benefit from simulation training in coronary anastomosis and more advanced procedures. We evaluated distributed practice using a portable task station and experience on a beating-heart model in training coronary anastomosis. METHODS: Eight cardiothoracic surgery residents performed 2 end-to-side anastomoses with the task station, followed by 2 end-to-side anastomoses to the left anterior descending artery by using the beating-heart model at 70 beats/min. Residents took home the task station, recording practice times. At 1 week, residents performed 2 anastomoses on the task station and 2 anastomoses on the beating-heart model. Performances of the anastomosis were timed and reviewed. RESULTS: Times to completion for anastomosis on the task station decreased 20% after 1 week of practice (351 +/- 111 to 281 +/- 53 seconds, P = .07), with 2 residents showing no improvement. Times to completion for beating-heart anastomosis decreased 15% at 1 week (426 +/- 115 to 362 +/- 94 seconds, P = .03), with 2 residents demonstrating no improvement. Home practice time (90-540 minutes) did not correlate with the degree of improvement. Performance rating scores showed an improvement in all components. Eighty-eight percent of residents agreed that the task station is a good method of training, and 100% agreed that the beating-heart model is a good method of training. CONCLUSIONS: In general, distributed practice with the task station resulted in improvement in the ability to perform an anastomosis, as assessed by times to completion and performance ratings, not only with the task station but also with the beating-heart model. Not all residents improved, which is consistent with a "ceiling effect" with the simulator and a "plateau effect" with the trainee. Simulation can be useful in preparing residents for coronary anastomosis and can provide an opportunity to identify the need and methods for remediation.

Congenital coronary artery anomalies presenting in late adulthood with concurrent acquired heart disease: report of two cases.

Congenital coronary anomalies can be found in up to 1% of patients undergoing angiography. The most severe of these lesions become symptomatic in early childhood, while others can remain without consequence. However, while being silent in the early decades of life, these asymptomatic anomalies can contribute to the presentation of acquired heart disease and can themselves become clinically significant. We describe the clinical course of two patients with congenital coronary artery anomalies presenting beyond the fifth decade of life with concurrent acquired heart disease.

The use of endobronchial valve device to eliminate air leak.

UNLABELLED: We evaluated an endobronchial valve device in the treatment of surgically created air leak or pneumothorax by eliminating antegrade flow. METHODS: Six sheep underwent general anesthesia with positive pressure ventilation and left thoracotomy. After division of the mediastinal pleura, the contralateral cranial lobe was identified and a 2.5 cmx1.5 cm laceration created with resultant air leak. Using bronchoscopy, we deployed a valve device in the bronchus of the injured segment. Chest drainage tube was placed and the thoracotomy closed. At 1 week (n=3) and 4 weeks (n=3), the animals underwent general anesthesia, bronchoscopy and right thoracotomy. RESULTS: All animals survived the procedure. Bronchoscopic valve device placement in the segmental bronchus resolved the air leak immediately. After closure of thoracotomy, the chest tube demonstrated minimal drainage with no air leak. At 1 and 4 weeks, bronchoscopy showed no change in device location, and the treated segments were atelectatic with fibrous scar at the injured site. CONCLUSIONS: Collapse of a selected lung segment with resolution of air leak can be achieved using bronchoscopically implanted valve device. The valve device may facilitate treatment of patients with post-surgical or post-traumatic persistent air leak.

Chronic mitral valve rejection requiring replacement in a nine-year-old allograft.

A 43-year-old woman underwent mitral valve replacement for severe mitral regurgitation nine years after orthotopic heart transplant. Histopathology showed chronic rejection of the mitral valve with lymphocytic infiltrates. The patient is well at one year follow-up. This report describes an identified case of chronic mitral valve rejection requiring valve replacement.

Cardiac allograft aortic dissection: successful repair using a composite valve graft and modified-Cabrol coronary reconstruction.

We report a 55-year-old man, the recipient of a cardiac allograft for ischemic cardiomyopathy 9 years earlier, who presented with progressive aortic root dilation, worsening aortic insufficiency, and an incidentally discovered chronic type A aortic dissection limited to the donor aorta. The patient was taken to the operating room, and the aortic dissection successfully repaired using standard reoperative techniques. This is the sixth case reported in the literature, and only the fourth survivor. To our knowledge, this case represents the first successful repair, of a limited aortic dissection of the donor aorta postcardiac transplantation, using a composite valve graft and modified-Cabrol coronary reconstruction.

Stat3-induced apoptosis requires a molecular switch in PI(3)K subunit composition.

Physiological apoptosis is induced by a switch from survival to death signalling. Dysregulation of this process is frequently associated with cancer. A powerful model for this apoptotic switch is mammary gland involution, during which redundant milk-producing epithelial cells undergo apoptosis. Signal transducer and activator of transcription 3 (Stat3) is an essential mediator of this switch but the mechanism has not yet been defined. Stat3-dependent cell death during involution can be blocked by activation of Akt/protein kinase B (PKB), a downstream effector of the phosphoinositide-3-OH kinase (PI(3)K) pathway. Here we show that expression of the PI(3)K regulatory subunits p55alpha and p50alpha is induced by Stat3 during involution. In the absence of Stat3 in vivo, upregulation of p55alpha and p50alpha is abrogated, levels of activated Akt are sustained and apoptosis is prevented. Chromatin immunoprecipitation assays show that Stat3 binds directly to the p55alpha and p50alpha promoters in vivo. Overexpression of either p55alpha or p50alpha reduces levels of activated Akt. We propose a novel mechanism in which Stat3 regulates apoptosis by inducing expression of distinct PI(3)K regulatory subunits to downregulate PI(3)K-Akt-mediated survival signalling.

Beating heart catheter-based edge-to-edge mitral valve procedure in a porcine model: efficacy and healing response.

BACKGROUND: Surgical edge-to-edge repair has been used in the treatment of mitral regurgitation. We evaluated the ability of a catheter-delivered clip (Evalve, Inc) to achieve edge-to-edge mitral valve approximation without cardiopulmonary bypass and the healing response of this technique. METHODS AND RESULTS: Twenty-one pigs underwent general anesthesia and left thoracotomy. A 10F flexible delivery catheter with a clip was placed into the left atrium. With echocardiographic and fluoroscopic guidance, the clip grasped and approximated the mid portion of the anterior and posterior leaflets. After a double orifice had been confirmed, the clip was detached and the catheter withdrawn. All animals survived and had successful clip placement. Three animals were euthanized at 4 weeks, 9 at 12 weeks, 1 at 17 weeks, 7 at 24 weeks, and 1 at 52 weeks. The clip was well positioned, with leaflet approximation in all animals except 1, in which the clip separated from the posterior leaflet at 4 weeks without affecting valve function. The clip was modified and implanted in 4 pigs; all were intact at 12 to 24 weeks. Scanning electron microscopy showed clip encapsulation with complete endothelialization. Mitral stenosis and thromboembolism did not develop. Two animals developed endocarditis (1 at 12 weeks and 1 at 17 weeks). Progressive healing occurred in all other animals. CONCLUSIONS: Edge-to-edge mitral valve approximation can be successfully and reliably achieved with a catheter-delivered clip without cardiopulmonary bypass, resulting in durable healing. The success of this device supports the development of a percutaneous catheter-based system for mitral valve repair.

Repair of Superior Vena Caval Perforation during Pacemaker Placement with Video-Assisted Limited Thoracotomy.

Abstract We report a case of a patient who sustained superior vena cava perforation just proximal to the innominate-caval confluence during pacemaker implantation. Because this complication was recognized early and the dilator was left in place, the patient remained hemodynamically stable and successfully underwent a videoscopically assisted repair of the superior vena caval perforation through a limited thoracotomy incision.