Deep Parasternal Intercostal Plane Block for Postoperative Analgesia After Sternotomy for Cardiac Surgery-A Retrospective Cohort Study.

OBJECTIVE: To examine the analgesic efficacy of postoperative deep parasternal intercostal plane (DPIP) blocks for patients having cardiac surgery via median sternotomy. DESIGN: This single-center retrospective study compared patients receiving bilateral DPIP blocks with a matched cohort of patients not receiving DPIP blocks. SETTING: Large quaternary referral center. PARTICIPANTS: Adult patients admitted to the authors' institution from January 1, 2016, to August 14, 2020, for elective cardiac surgery via median sternotomy. INTERVENTIONS: Patients received ultrasound-guided bilateral DPIP blocks. MEASUREMENTS AND MAIN RESULTS: A total of 113 patients received a DPIP block; 3,461 patients did not. The estimated multiplicative change in cumulative opioid consumption through 24 hours was 0.42 (95% CI 0.32-0.56; p < 0.001), indicating that patients receiving DPIP blocks required 60% fewer opioids than patients who did not. Proportional odds ratios for the average pain score on postoperative day (POD) 0 was 0.46 (95% CI 0.32-0.65; p < 0.001), and POD 1 was 0.67 (95% CI 0.47-0.94; p = 0.021), indicating lower pain scores for patients receiving blocks. The exploratory analysis identified an inverse correlation between DPIP blocks and atrial fibrillation incidence (2% v 15%; inverse probability of treatment weighting odds ratio 0.088, 95% CI 0.02-0.41; p = 0.002). CONCLUSIONS: The use of DPIP blocks in patients undergoing cardiac surgery via median sternotomy was associated with less opioid use and improved pain scores in the early postoperative period compared with patients not receiving blocks. Prospective randomized controlled studies should further elucidate the efficacy and risks of DPIP blocks in cardiac surgery.

Obesity and vascular complication in percutaneous transfemoral transcatheter aortic valve insertion.

BACKGROUND: Obesity has been associated with an increased risk of vascular complication during percutaneous coronary intervention, but there are no data on the risk of vascular complication during percutaneous transfemoral transcatheter aortic valve insertion (TAVI). OBJECTIVES: We hypothesized there would be a similar increased risk associated with TAVI. METHODS: We reviewed the records of 1176 patients who received percutaneous transfemoral transcatheter aortic valve insertion from September 2015 to September 2020. All patients received 1) preoperative computed tomoraphy angiography assessment of the abdomen and pelvis to delineate iliofemoral artery anatomy, 2) ultrasound-guided percutaneous femoral arterial access, and 3) pre-closure of the delivery sheath femoral access site. Vascular complication was recorded based on definitions set forth by Valve Academic Research Consortium 3. RESULTS: The median age of patients was 81 years, and 60% were men. The median body mass index (BMI) was 29 kg/m2 (range, 11-67), and 91 (8%) patients had a value ≥40 kg/m2 (i.e., morbid obesity). Delivery sheath size was 14-French in 859 (73%) patients, 16-French in 311 (26%), and 18-French in 6 (1%). Vascular complication occurred in 53 (5%) patients, including 39 (7%) among the first half of procedures and 14 (2%) among the second half (p < 0.001). When stratified by obesity status (BMI < or ≥30 kg/m2 , p < 0.001), the complication rate was 4% in nonobese patients and 5% in obese patients. Multivariable analysis showed no overall association between risk of vascular complication and BMI categories (p = 0.583)BMI continuous values (p = 0.529), or sheath size (p = 0.217). CONCLUSIONS: Obesity is not associated with a vascular complication during percutaneous transfemoral transcatheter aortic valve insertion. The operation should not be denied in obese patients.

Pectoral Fascial Plane Versus Paravertebral Blocks for Minimally Invasive Mitral Valve Surgery Analgesia.

OBJECTIVES: This study examined the postoperative analgesic efficacy of single-injection pectoral fascial plane (PECS) II blocks compared to paravertebral blocks for elective robotic mitral valve surgery. DESIGN: A single-center retrospective study that reported patient and procedural characteristics, postoperative pain scores, and postoperative opioid use for patients undergoing robotic mitral valve surgery. SETTING: This investigation was performed at a large quaternary referral center. PARTICIPANTS: Adult patients (age ≥18) admitted to the authors' hospital from January 1, 2016, to August 14, 2020, for elective robotic mitral valve repair who received either a paravertebral or PECS II block for postoperative analgesia. INTERVENTIONS: Patients received an ultrasound-guided, unilateral paravertebral or PECS II nerve block. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three patients received a PECS II block, and 190 patients received a paravertebral block during the study period. The primary outcome measures were average postoperative pain scores and cumulative opioid use. Secondary outcomes included hospital and intensive care unit lengths of stay, need for reoperation, need for antiemetics, surgical wound infection, and atrial fibrillation incidence. Patients receiving the PECS II block required significantly fewer opioids in the immediate postoperative period than the paravertebral block group, and had comparable postoperative pain scores. No increase in adverse outcomes was noted for either group. CONCLUSIONS: The PECS II block is a safe and highly effective option for regional analgesia for robotic mitral valve surgery, with demonstrated efficacy comparable to the paravertebral block.

Evaluation of the Educational Value of Low-Cost Training Model for Emergency Cricothyrotomy.

BACKGROUND: In this study, we aimed to evaluate the educational value and students' satisfaction with the hand-made low-cost cricothyrotomy simulation model. MATERIALS AND METHODS: A low-cost and hand-made model and a high-fidelity model were used to assess the students. The students' knowledge and satisfaction were evaluated using a 10-item checklist and a satisfaction questionnaire, respectively. Medical interns in the present study participated in a two-hour briefing and debriefing session held in the Clinical Skills Training Center by an emergency attending doctor. RESULTS: Based on the results of data analysis, no significant differences were found between the two groups in terms of gender, age, the month of internship, and last semester's grade (P = .628, .356, .847, and .421, respectively). We also found no significant differences between our groups in terms of the median score of each item in the assessment checklist (P = .838, .736, .805, .172, .439, .823, .243, .950, .812, and .756, respectively). The study groups had no significant difference in the median total scores of the checklist as well (P = .504). Regarding the students' satisfaction, our results showed that interns evaluated their experience of the model as positive (median scores of 4 and 5 out of 5). They also gave the hand-made model a median score of 7 in comparison with the high-fidelity model and 8 out of 10 for its usability. CONCLUSION: The study results showed that a low-cost model could be as effective as an expensive high-fidelity model for teaching the necessary knowledge of cricothyrotomy techniques to medical trainees.

Robotic vs. minimally invasive mitral valve repair: A 5-year comparison of surgical outcomes.

BACKGROUND: Minimally invasive mitral valve repair (MVr) is commonly performed. Data on the outcomes of robotic MVr versus nonrobotic minimally invasive MVr are lacking. We sought to compare the short-term and mid-term outcomes of robotic and nonrobotic MVr. METHODS: We reviewed all patients who underwent robotic MVr (n = 424) or nonrobotic MVr via right mini-thoracotomy (n = 86) at Mayo Clinic, Rochester, MN, from January 2015 to February 2020. Data on baseline and operative characteristics, operative and long-term outcomes were analyzed. Patients were matched 1:1 using propensity scores. RESULTS: Sixty-nine matched pairs were included in the study. The median age was 59 years (interquartile range [IQR]: 54-69) and 75% (n = 103) were male. Baseline characteristics were similar after matching. Robotic and nonrobotic MVr had similar operative characteristics, except that robotic had longer cross-clamp times (57 [48-67] vs. 47 [37-58] min, p < .001) and more P2 resections (83% vs. 68%, p = .05) compared to nonrobotic MVr. There was no difference in operative outcomes between groups. Hospital stay was shorter after robotic MVr (4 [3-4] vs. 4 [4-6] days, p = .003). After a median follow-up of 3.3 years (IQR, 2.1-4.5), there was no mortality in either group, and there was no difference in freedom from mitral valve reoperations between robotic and nonrobotic MVr (5 years: 97.1% vs. 95.7%, p = .63). Follow-up echocardiogram analysis predicted excellent freedom from recurrent moderate-or-severe mitral regurgitation at 3 years after robotic and nonrobotic MVr (90% vs. 92%, p = .18, respectively). CONCLUSIONS: Both short-term and mid-term outcomes of robotic and nonrobotic minimally invasive mitral repair surgery are comparable.

Outcomes of Coronary Artery Bypass Grafting in Patients With Poor Myocardial Viability: A Systematic Review and Meta-Analysis of the Last Decade.

OBJECTIVES: Our objective is to assess whether the presence of myocardial viability is a predictor of mortality among patients undergoing coronary artery bypasss grafting (CABG) through a systematic review meta-analysis. METHODS: Comprehensive review of EMBASE and PubMed in accordance with PRISMA guidelines, including studies of patients undergoing CABG with assessment of myocardial viability and recorded long-term mortality, age and sex. Studies were restricted to the last decade, and data were stratified by imaging modality (magnetic resonance imaging [MRI] or nuclear medicine). Random-effects model for assessing pooled effect, heterogeneity assessment using Chi-square and I2 statistics, publication bias assessed by funnel plots and Egger's test. RESULTS: Meta-analysis of contemporary data (January 2010 to October 2020) yielded 3,621 manuscripts of which 92 were relevant, and 6 appropriate for inclusion with 993 patients. Pooled analysis showed that patients with non-viable myocardium undergoing CABG are at 1.34 times the risk of mortality compared to those with viable myocardium (95% CI 1.01-1.79, p=0.05). Subgroup analysis of the MRI or nuclear medicine modalities was not statistically significant and there was no confounding by age or sex in meta-regression. There was significant heterogeneity in imaging modality and diagnostic criteria, but heterogeneity between study findings was low with an I2 statistic of 29%. The risk of publication bias was moderate on the Newcastle-Ottawa Scale), but not statistically significant (Egger's Test coefficient=1.3, 95%CI -0.35-2.61, p=0.10). CONCLUSIONS: There is a multitude of methods for assessing cardiac viability for coronary revascularisation surgery, making meta-analyses fraught with limitations. Our meta-analysis demonstrates that the finding of non-viable myocardium can not be used draw conclusions for risk assessment in coronary surgery.

Open staged repair of splenic and extensive superior mesenteric artery aneurysms.

A 31-year-old man with a history of multiple strokes of unknown etiology presented with multiple asymptomatic visceral artery aneurysms including a 3.3-cm bilobed splenic artery aneurysm and a 3.1-cm fusiform superior mesenteric artery aneurysm. He had no family history of aneurysms, and there was no evidence of collagen disease. He underwent open splenic artery aneurysm resection without splenectomy and had an uneventful recovery. Seven months later, he had open repair of his 14.6-cm-long fusiform superior mesenteric artery aneurysm with a 15-cm-long collagen-coated polyester interposition graft with multiple visceral branch reimplantations into the graft. The postoperative course was uneventful, and computed tomography confirmed patent graft and side branches. Two years later, the patient remained free of abdominal symptoms, although he suffered another episode of a mild stroke.

Robotic single-site adrenalectomy.

INTRODUCTION: Technological advances have brought about robotic single-site (RSS) cholecystectomy and hysterectomy. The application of RSS to additional procedures requires careful assessment of the surgeon learning curve, the technological limitations, patient selection criteria and associated outcomes. METHODS: Patient demographics, BMI, surgical indications, adrenal size, OR times, length of stay, postoperative pain and complications were assessed. RESULTS: Thirty-three patients underwent RSS-A by a single surgeon with 53 % being male, mean age 54 ± 16 years and mean BMI of 32.7. There were 18 left, 10 right, and 5 bilateral procedures for a total of 38 adrenal glands removed (mean tumor size 3.2 cm). There were 5 conversions to a laparoscopic approach, and two to open approach. The necessity for conversion was not associated with age, BMI, tumor size, surgical side or pathology (p > 0.05). The patients who underwent successful unilateral RSS-A had a profile of mean age 55, BMI 31, tumor size 3 cm, and a mean operative time of 118 ± 25.8 min. Pain scores were <4 (10 point scale) in 67 % of patients. 74 % of patients were discharged on POD 1 and 96 % were discharged by POD 2. An assessment of the quartile learning curve for the unilateral RSS-A showed operative times decreased from a mean of 124 to 103 min after 21 cases (p = 0.05). CONCLUSION: Patients with functioning and non-functioning tumors, along with those with obesity can safely be treated with RSS-A. The surgeon learning curve was associated with shortened operative times and not increased complication rates.

Navigating missing link: innovative cannulation for robotic mitral valve repair in the absence of inferior vena cava.

Cardiac surgeries often require the use of cardiopulmonary bypass to allow visualization and manipulation of tissues. Vascular anomalies may impose challenges with access configuration. A patient was evaluated for robot-assisted mitral valve repair and found to have an atretic inferior vena cava secondary due to chronic occlusion. The patient was cannulated arterially through the left common femoral artery, and two cannulation sites were applied for venous drainage: the right intrajugular vein and a second percutaneous access site directly into the right atrium through the chest wall. The procedure was completed without immediate complications, and the patient's perioperative course was unremarkable.

Long-term Stroke and Mortality Risk in Nonagenarians After Transcatheter Aortic Valve Insertion.

BACKGROUND: Limited data exist on the long-term outcomes of transcatheter aortic valve insertion (TAVI) in nonagenarian patients. This study investigated the relationship between patient baseline comorbidity and frailty on the long-term outcome of the nonagenarian population. METHODS: A retrospective analysis was conducted of 187 consecutive nonagenarian patients who underwent TAVI from 2009 to 2020. Multivariable models were used to analyze the association between baseline patient and frailty variables and mortality, stroke, and repeat hospitalization. Long-term survival was compared with an age- and sex-matched United States population. RESULTS: The median Society of Thoracic Surgeons predicted risk of mortality was 10% (interquartile range, 7%-17%). Frailty was met in 72% of patients based on the 5-meter walk test, 13% based on the Kansas City Cardiomyopathy Questionnaire 12-item instrument score, 12% based on Katz Index of Independence in Activities of Daily Living, and 8% based on serum albumin levels. Procedure-related death occurred in 3 patients (2%) and stroke in 8 (4%). The median duration of follow-up was 3.4 years. Outcomes included death in 150 patients (80%), stroke in 15, and repeat hospitalization in 114. Multivariable analysis identified no association between any of the baseline patient variables with mortality, stroke, repeat hospitalization, or the combined outcomes (all P > .05). The 1- and 5-year survival rates in TAVI-treated nonagenarians were similar to age- and sex-matched controls (P = .27). CONCLUSIONS: Long-term death or stroke is independent of The Society of Thoracic Surgeons predicted risk of mortality and frailty risk variables in this nonagenarian patient population who received TAVI. Furthermore, survival is similar to age- and sex-matched controls.

Single-Center Prospective Study of Cross-Clamp vs Balloon Occlusion in Robotic Mitral Surgery.

BACKGROUND: Transthoracic aortic cross-clamp and endoaortic balloon occlusion have both been shown to have comparable safety profiles for aortic occlusion. Because most surgeons use only one technique, we sought to compare the outcomes when a homogeneous group of surgeons changed their occlusion technique from aortic cross-clamp to balloon occlusion. METHODS: We changed our technique from aortic cross-clamp to balloon occlusion in November 2022. This allowed us to conduct a prospective treatment comparison study in the same group of surgeons. Propensity score matching was used to match cases (balloon occlusion) 1:3 to controls (aortic cross-clamp) based on age, sex, body mass index, concomitant maze procedure, and tricuspid valve repair. RESULTS: Total of 411 patients underwent robotic mitral surgery from 2020 through 2023. Propensity score matching was used to match 56 balloon occlusion patients to 168 aortic cross-clamp patients. The 224 patients were a median age of 65 years (interquartile range, 55.6-70.0 years), and 119 (53%) were men. All valves were successfully repaired. Balloon occlusion had a shorter median cardiopulmonary bypass (CPB) time compared with aortic cross-clamp (84.0 vs 94.5 minutes, P = .006). Median cross-clamp time (64.0 vs 64.0 minutes, P = .483) and total surgery time (5.9 vs 6.1 hours, P = .495) did not differ between groups. There were no in-hospital deaths. There were 5 surgeons who performed various combinations of console and bedside roles. CPB, cross-clamp, and surgery durations were not significantly affected by the different surgeon combinations. CONCLUSIONS: Compared with aortic cross-clamp, balloon occlusion has similar perioperative and early postoperative outcomes. Additionally, it likely introduces a 10-minute reduction in total CPB time.

Simultaneous Tricuspid Valve Repair at the Time of Mitral Valve Surgery: Determinants of Postoperative Pacemaker Implantation.

OBJECTIVE: Guidelines recommend tricuspid valve (TV) repair for patients with severe tricuspid valve regurgitation (TR) undergoing surgery for degenerative mitral valve (MV) disease, but management of ≤ moderate TR is controversial. This study examines the incidence and causes of bradyarrhythmias leading to PPM implantation. METHODS: Review of patients undergoing simultaneous TV repair and MV surgery for degenerative MV disease from 2001 to 2022 (N=404). Primary endpoint was the incidence of postoperative PPM implantation. Secondary endpoints included the incidence of high-degree AV block and overall survival. RESULTS: All patients underwent TV repair at the time of MV surgery; 332 (82%) underwent MV repair and 72 (18%) MV replacement. Tricuspid valve repair techniques included flexible band (n=258, 63.8%), DeVega annuloplasty (n=78, 19.3%), complete flexible ring (n=49, 12.1%), and incomplete rigid ring (n=19, 4.7%). The 30-day mortality was 0.5% (n=2). A total of 35 (8.7%) patients had a PPM implanted postoperatively, 26 (6.4%) for high-degree AV block. On multivariable analysis, only older age was associated with PPM implantation. Patients who received a PPM due to high-degree AV block had reduced overall survival (Figure, p=0.01). CONCLUSIONS: Need for permanent pacing following TV repair at the time of MV surgery is not uncommon, but there are few modifiable factors that might reduce this risk. Careful selection of patients with less-than-severe TR and surgical techniques may reduce PPM-related risks and complications.

The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2023 Update on Procedure Data and Research.

The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database is one of the largest and most comprehensive contemporary clinical databases in use. It now contains >9 million procedures from 1010 participants and 3651 active surgeons. Using audited data collection, it has provided the foundation for multiple risk models, performance metrics, health policy decisions, and a trove of research studies to improve the care of patients in need of cardiac surgical procedures. This annual report provides an update on the current status of the database and summarizes the development of new risk models and the STS Online Risk Calculator. Further, it provides insights into current practice patterns, such as the change in the demographics among patients undergoing aortic valve replacement, the use of minimally invasive techniques for valve and bypass surgery, or the adoption of surgical ablation and left atrial appendage ligation among patients with atrial fibrillation. Lastly, an overview of the research conducted using the STS Adult Cardiac Surgery Database and future directions for the database are provided.

Case Report: A myxoma with a far reach.

A 73-year-old woman presented to the emergency department with a syncopal episode and a history of dizzy spells. A transthoracic echocardiogram demonstrated a large left atrial mass extending into the right upper pulmonary veins. Subsequently, cardiac magnetic resonance imaging and coronary computed tomography angiography with three-dimensional reconstruction and printing of the heart and mass were performed, which demonstrated a high index of suspicion for an atypical left atrial myxoma. The mass was excised robotically, and the pathology report confirmed a diagnosis of myxoma.

A Case Series of Minimally Invasive Robotic-Assisted Resection of Cardiac Papillary Fibroelastoma: The Mayo Clinic Experience.

Papillary fibroelastomas (PFEs) are small, slowly growing benign cardiac tumors with clinically significant risk of embolization. Surgical excision is the definitive treatment of symptomatic PFE and is conventionally performed through a median sternotomy. In this study, we report a series of 12 patients, who underwent robotic-assisted PFE removal at the Mayo Clinic. PFE involved the mitral valve, left atrium, and tricuspid valve. No major complications occurred after the procedure, and most patients were discharged 4 days after the surgery. On follow-up, 1 patient demonstrated pericarditis.

Predicting postoperative systolic dysfunction in mitral regurgitation: CT vs. echocardiography.

Introduction: Volume overload from mitral regurgitation can result in left ventricular systolic dysfunction. To prevent this, it is essential to operate before irreversible dysfunction occurs, but the optimal timing of intervention remains unclear. Current echocardiographic guidelines are based on 2D linear measurement thresholds only. We compared volumetric CT-based and 2D echocardiographic indices of LV size and function as predictors of post-operative systolic dysfunction following mitral repair. Methods: We retrospectively identified patients with primary mitral valve regurgitation who underwent repair between 2005 and 2021. Several indices of LV size and function measured on preoperative cardiac CT were compared with 2D echocardiography in predicting post-operative LV systolic dysfunction (LVEFecho <50%). Area under the curve (AUC) was the primary metric of predictive performance. Results: A total of 243 patients were included (mean age 57 ± 12 years; 65 females). The most effective CT-based predictors of post-operative LV systolic dysfunction were ejection fraction [LVEFCT; AUC 0.84 (95% CI: 0.77-0.92)] and LV end systolic volume indexed to body surface area [LVESViCT; AUC 0.88 (0.82-0.95)]. The best echocardiographic predictors were LVEFecho [AUC 0.70 (0.58-0.82)] and LVESDecho [AUC 0.79 (0.70-0.89)]. LVEFCT was a significantly better predictor of post-operative LV systolic dysfunction than LVEFecho (p = 0.02) and LVESViCT was a significantly better predictor than LVESDecho (p = 0.03). Ejection fraction measured by CT demonstrated significantly greater reproducibility than echocardiography. Discussion: CT-based volumetric measurements may be superior to established 2D echocardiographic parameters for predicting LV systolic dysfunction following mitral valve repair. Validation with prospective study is warranted.

Restricted cusp motion in newly implanted tricuspid bioprostheses: Incidence, predictors, and impact on survival.

OBJECTIVE: To investigate the occurrence of restricted cusp motion (RCM) at the time of bioprosthetic tricuspid valve replacement (TVR) and analyze associated risk factors and outcomes. METHODS: This study involved adult patients who underwent TVR with a bioprosthesis at our institution between 2012 and 2022. Bioprosthetic cusp motion was analyzed de novo through a detailed review of intraoperative transesophageal echocardiograms (TEE). Two models of porcine valves were implanted: the Medtronic Hancock II bioprosthesis and the St Jude Medical Epic bioprosthesis. RESULTS: Among the 476 patients who met the inclusion criteria, RCM was identified on immediate post-bypass TEE in 150 (31.5%); there was complete immobility of the cusp in 63 patients (13.2%) and limited movement of a cusp in 87 patients (18.3%). In a multivariable logistic regression analysis, the Hancock II model (odds ratio [OR], 6.15; P < .001), a larger orifice area (per IQR increase: OR, 1.58; P = .017), a smaller body surface area (per IQR increase: OR, .68; P = .040), and a lower ejection fraction (per IQR increase: OR, .60; P = .033) were independently associated with having RCM. Cox regression adjusting for 15 covariates revealed that RCM at the time of TVR was independently associated with an increased risk of mortality (hazard ratio, 1.35; P = .049). CONCLUSIONS: This study revealed a high incidence of RCM in bioprosthetic valves in the tricuspid position detected shortly postimplantation, which was associated with increased late mortality. To reduce the probability of RCM, it is important to select the appropriate prosthesis model and size, particularly in small patients.

Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial.

Background: RBT-1 is a combination drug of stannic protoporfin (SnPP) and iron sucrose (FeS) that elicits a preconditioning response through activation of antioxidant, anti-inflammatory, and iron-scavenging pathways, as measured by heme oxygenase-1 (HO-1), interleukin-10 (IL-10), and ferritin, respectively. Our primary aim was to determine whether RBT-1 administered before surgery would safely and effectively elicit a preconditioning response in patients undergoing cardiac surgery. Methods: This phase 2, double-blind, randomised, placebo-controlled, parallel-group, adaptive trial, conducted in 19 centres across the USA, Canada, and Australia, enrolled patients scheduled to undergo non-emergent coronary artery bypass graft (CABG) and/or heart valve surgery with cardiopulmonary bypass. Patients were randomised (1:1:1) to receive either a single intravenous infusion of high-dose RBT-1 (90 mg SnPP/240 mg FeS), low-dose RBT-1 (45 mg SnPP/240 mg FeS), or placebo within 24-48 h before surgery. The primary outcome was a preoperative preconditioning response, measured by a composite of plasma HO-1, IL-10, and ferritin. Safety was assessed by adverse events and laboratory parameters. Prespecified adaptive criteria permitted early stopping and enrichment. This trial is registered with ClinicalTrials.gov, NCT04564833. Findings: Between Aug 4, 2021, and Nov 9, 2022, of 135 patients who were enrolled and randomly allocated to a study group (46 high-dose, 45 low-dose, 44 placebo), 132 (98%) were included in the primary analysis (46 high-dose, 42 low-dose, 44 placebo). At interim, the trial proceeded to full enrollment without enrichment. RBT-1 led to a greater preconditioning response than did placebo at high-dose (geometric least squares mean [GLSM] ratio, 3.58; 95% CI, 2.91-4.41; p < 0.0001) and low-dose (GLSM ratio, 2.62; 95% CI, 2.11-3.24; p < 0.0001). RBT-1 was generally well tolerated by patients. The primary drug-related adverse event was dose-dependent photosensitivity, observed in 12 (26%) of 46 patients treated with high-dose RBT-1 and in six (13%) of 45 patients treated with low-dose RBT-1 (safety population). Interpretation: RBT-1 demonstrated a statistically significant cytoprotective preconditioning response and a manageable safety profile. Further research is needed. A phase 3 trial is planned. Funding: Renibus Therapeutics, Inc.

Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice.

The purpose of this study was to characterize changes in antioxidant and age-related gene expression in aorta and aortic valve with aging, and test the hypothesis that increased mitochondrial oxidative stress accelerates age-related endothelial and aortic valve dysfunction. Wild-type (MnSOD(+/+)) and manganese SOD heterozygous haploinsufficient (MnSOD(+/-)) mice were studied at 3 and 18 mo of age. In aorta from wild-type mice, antioxidant expression was preserved, although there were age-associated increases in Nox2 expression. Haploinsufficiency of MnSOD did not alter antioxidant expression in aorta, but increased expression of Nox2. When compared with that of aorta, age-associated reductions in antioxidant expression were larger in aortic valves from wild-type and MnSOD haploinsufficient mice, although Nox2 expression was unchanged. Similarly, sirtuin expression was relatively well-preserved in aorta from both genotypes, whereas expression of SIRT1, SIRT2, SIRT3, SIRT4, and SIRT6 were significantly reduced in the aortic valve. Expression of p16(ink4a), a marker of cellular senescence, was profoundly increased in both aorta and aortic valve from MnSOD(+/+) and MnSOD(+/-) mice. Functionally, we observed comparable age-associated reductions in endothelial function in aorta from both MnSOD(+/+) and MnSOD(+/-) mice. Interestingly, inhibition of NAD(P)H oxidase with apocynin or gp91ds-tat improved endothelial function in MnSOD(+/+) mice but significantly impaired endothelial function in MnSOD(+/-) mice at both ages. Aortic valve function was not impaired by aging or MnSOD haploinsufficiency. Changes in antioxidant and sirtuin gene expression with aging differ dramatically between aorta and aortic valve. Furthermore, although MnSOD does not result in overt cardiovascular dysfunction with aging, compensatory transcriptional responses to MnSOD deficiency appear to be tissue specific.

Operative management after transcatheter aortic valve replacement.

With broadening applications of transcatheter aortic valve replacement (TAVR) and increasing use in intermediate- and low-risk patients, the incidence of surgical re-interventions after TAVR is growing. Transcatheter heart valves suffer from similar long-term complications as surgical heart valve prostheses that require surgical re-intervention, including endocarditis and structural valve deterioration. Catastrophic periprocedural complications - such as annular or aortic rupture requiring urgent surgical intervention - may also occur during TAVR procedures. This review summarizes the current knowledge on indications, methods, and outcomes of cardiac operations after TAVR, with a focus on how to improve results in a rapidly growing patient population.