Impact of nondiameter aortic indices on surgical eligibility: Results from the Treatment in Thoracic Aortic Aneurysm: Surgery Versus Surveillance (TITAN: SvS) randomized controlled trial.

OBJECTIVES: Traditional criterion for intervention on an asymptomatic ascending aortic aneurysm has been a maximal aortic diameter of 5.5 cm or more. The 2022 American College of Cardiology/American Heart Association aortic guidelines adopted cross-sectional aortic area/height ratio, aortic size index, and aortic height index as alternate parameters for surgical intervention. The objective of this study was to evaluate the impact of using these newer indices on patient eligibility for surgical intervention in a prospective, multicenter cohort with moderate-sized ascending aortic aneurysms between 5.0 and 5.4 cm. METHODS: Patients enrolled from 2018 to 2023 in the randomization or registry arms of the multicenter trial, Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance, were included in the study. Clinical data were captured prospectively in an online database. Imaging data were derived from a core computed laboratory. RESULTS: Among the 329 included patients, 20% were female. Mean age was 65.0 ± 11.6 years, and mean maximal aortic diameter was 50.8 ± 3.9 mm. In the one-third of all patients (n = 109) who met any 1 of the 3 criteria (ie, aortic size index ≥3.08 cm/m2, aortic height index ≥3.21 cm/m, or cross-sectional aortic area/height ≥ 10 cm2/m), their mean maximal aortic diameter was 52.5 ± 0.52 mm. Alternate criteria were most commonly met in women compared with men: 20% versus 2% for aortic size index (P < .001), 39% versus 5% for aortic height index (P < .001), and 39% versus 21% for cross-sectional aortic area/height (P = .002), respectively. CONCLUSIONS: One-third of patients in Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance would meet criteria for surgical intervention based on novel parameters versus the classic definition of diameter 5.5 cm or more. Surgical thresholds for aortic size index, aortic height index, or cross-sectional aortic area/height ratio are more likely to be met in female patients compared with male patients.

Edge-to-edge with partial band mitral valve repair compared to replacement and undersized restrictive annuloplasty for ischemic mitral regurgitation.

Objective: Evidence supports replacement over repair for ischemic mitral regurgitation due to improved durability; however, the latter often involves an undersized ring annuloplasty that does not include edge-to-edge approximation. The objective of this study was to evaluate the outcomes of replacement, edge-to-edge leaflet approximation with mild-undersized annuloplasty and undersized ring annuloplasty for ischemic mitral regurgitation. Methods: This is a single-center retrospective study of patients undergoing mitral surgery for moderate-severe or greater ischemic mitral regurgitation, between 2004 and 2020, with mild-undersized annuloplasty, mitral valve replacement, or undersized restrictive annuloplasty (undersized ring annuloplasty). The primary outcome was all-cause mortality. Secondary outcomes included first recurrence of mitral regurgitation, heart failure hospitalization, and composite of valve-related events (bleeding, thromboembolism, endocarditis, and mitral valve reoperation). Results: There were 121, 93, and 78 patients in the mitral valve replacement, mild-undersized annuloplasty, and undersized restrictive annuloplasty groups, respectively, with a median follow-up of 3.1, 5.9, and 3.8 years, respectively. Both mitral valve replacement (hazard ratio, 1.87; 95% CI, 1.029-3.415) and undersized restrictive annuloplasty (hazard ratio, 2.73; 95% CI, 1.480-5.061) were associated with worse survival compared with mild-undersized annuloplasty. At 2 years, the rate of mild-moderate mitral regurgitation was greater in the mild-undersized annuloplasty group compared with the mitral valve replacement group (P = .001) but less than in the undersized restrictive annuloplasty group (P = .001). The rate of recurrent moderate or greater mitral regurgitation at 2 years was similar between mild-undersized annuloplasty and mitral valve replacement groups but significantly higher after undersized restrictive annuloplasty (P < .0001). Mitral valve replacement and undersized restrictive annuloplasty were associated with a significant increase in the incidence of first heart failure hospitalization compared with mild-undersized annuloplasty (P < .001 and P = .001, respectively). Mitral valve replacement was associated with an increased incidence of valve-related events compared with mild-undersized annuloplasty (P = .002). Conclusions: Surgical edge-to-edge approximation in addition to a mild-undersizing annuloplasty offers similar durability compared with replacement, with a lower rate of hospitalization for heart failure, and may confer a survival advantage.

Comparison of the efficacy of steroid-free versus classic steroid-containing regimens in primary membranous nephropathy.

Objective: To compare the efficacy of a steroid-free regimen with steroid-based treatment in managing primary membranous nephropathy (PMN) and investigate the potential benefits of steroid-free regimens in PMN therapy. Methods: This was a single-centre prospective cohort study. A total of 81 patients were divided into two groups according to their medication regimen: a rituximab (RTX)/tacrolimus (TAC) group (low-dose RTX combined with low-dose TAC group, without steroids, n = 31) and a prednisone (P)/TAC group (P combined with TAC group, n = 61). The changes in 24-h urine protein quantification, levels of blood albumin, blood creatinine, total cholesterol, triglyceride and fasting blood glucose as well as anti-phospholipase A2 receptor antibody titres were observed in both groups before treatment and after 1, 3, 6 and 12 months of treatment. Clinical remission (complete and partial remission), serological remission and recurrence were assessed in both groups after treatment, and the occurrence of adverse reactions was observed. Results: 1) Before treatment, there was no significant difference in baseline values between the two groups (p > 0.05). 2) After 12 months of treatment, the 24-h proteinuria and total cholesterol levels in the RTX/TAC group were significantly lower than those in the P/TAC group (p < 0.05). 3) After 6 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). After 12 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). (4) After 3, 6 and 12 months of treatment, serological remission rates in the RTX/TAC group were significantly higher than those in the P/TAC group (p < 0.05). During treatment, the anti-PLA2R antibody titres in the RTX/TAC group remained lower than those in the P/TAC group (p < 0.05). Conclusion: The low-dose RTX combined with low-dose TAC steroid-free regimen induces serological remission in patients with PMN earlier than the classic regimen of P combined with TAC, and there was no significant difference in adverse effects between the two groups. Besides, the long-term clinical remission effect of low-dose RTX combined with low-dose TAC is better than that of P combined with TAC.

Long-term survival, cardiovascular, and functional outcomes after minimally invasive coronary artery bypass grafting in 566 patients.

OBJECTIVE: Sternotomy has been the gold standard incision for surgical revascularization but may be associated with chronic pain and sternal malunion. Minimally invasive coronary artery bypass grafting allows for complete surgical revascularization through a small thoracotomy in selected patients. There is a paucity of long-term data, particularly functional outcomes, for patients who underwent minimally invasive coronary artery bypass grafting. METHODS: Patients (N = 566) who underwent minimally invasive coronary artery bypass grafting at a single institution over a 17-year period were prospectively followed. The primary outcome was survival. At late follow-up, patients were contacted for a questionnaire on functional outcomes. Multivariable Cox proportional hazard model identified correlates of the primary outcome. RESULTS: Clinical follow-up was complete for 100% of patients (mean 7.0 ± 4.4 years); a follow-up questionnaire was also completed for 83.9% (N = 427) of live patients. Fifty percent of patients (N = 283) had undergone multivessel grafting. At 12 years, survival for the entire cohort was 82.2% ± 2.6%. On late follow-up questionnaire, 12 patients (2.8%) had greater than Canadian Cardiovascular Score Class II angina and 19 patients (4.5%) had greater than New York Heart Association Class II symptoms. More than 98% of patients did not have pain related to the incision site. Cox proportional hazards analysis identified older age, peripheral vascular disease, prior myocardial infarction, left ventricular dysfunction, cancer in the past 5 years, intraoperative transfusion, and hybrid revascularization as correlates of mortality during follow-up. CONCLUSIONS: Minimally invasive coronary artery bypass grafting is a safe and durable alternative to sternotomy coronary artery bypass grafting in selected patients, with excellent short- and long-term outcomes, including for multivessel coronary disease. At long-term follow-up, the proportion of patients with significant symptoms and incisional pain was low.

Influence of preoperative frailty on quality of life after cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Frailty has emerged as an important prognostic marker of increased mortality after cardiac surgery, but its association with quality of life (QoL) and patient-centered outcomes is not fully understood. We sought to evaluate the association between frailty and such outcomes in older patients undergoing cardiac surgery. METHODS: This systematic review included studies evaluating the effect of preoperative frailty on QoL outcomes after cardiac surgery amongst patients 65 years and older. The primary outcome was patient's perceived change in QoL following cardiac surgery. Secondary outcomes included residing in a long-term care facility for 1 year, readmission in the year following the intervention, and discharge destination. Screening, inclusion, data extraction, and quality assessment were performed independently by two reviewers. Meta-analyses based on the random-effects model were conducted. The evidential quality of findings was assessed with the GRADE profiler. RESULTS: After the identification of 3105 studies, 10 observational studies were included (1580 patients) in the analysis. Two studies reported on the change in QoL following cardiac surgery, which was higher for patients with frailty than for patients without. Preoperative frailty was associated with both hospital readmission (pooled odds ratio [OR] 1.48 [0.80-2.74], low GRADE level) as well as non-home discharge (pooled OR 3.02 [1.57-5.82], moderate GRADE level). CONCLUSION: While evidence in this field is limited by heterogeneity of frailty assessment and non-randomized data, we demonstrated that baseline frailty may possibly be associated with improved QoL, but with increased readmission as well as discharge to a non-home destination following cardiac surgery. These patient-centered outcomes are important factors when considering interventional options for older patients. STUDY REGISTRATION: OSF registries (https://osf.io/vm2p8).

Design, synthesis and anti-inflammatory activity of diterpenoid alkaloids and non-steroidal anti-inflammatory drug hybrids based on molecular hybridization strategy.

Molecular hybridization is a widely employed approach in pharmaceutical chemistry for modifying drugs with the aim of improving pharmacological efficacy and reducing adverse effects. A prime example of this is the case of benorylate, which was created by combining aspirin and acetaminophen, two non-steroidal anti-inflammatory drugs (NSAIDs). Diterpenoid alkaloids, which exhibit potent anti-inflammatory activity, have limitations in their application due to their toxicity and side effects. Thus, we aimed to design new anti-inflammatory lead compounds through the molecular hybridization of the anti-inflammatory active skeletons (lappaconitine, aconorine, and bulleyaconitine A) of diterpenoid alkaloids with classical NSAIDs. In this study, we synthesized 25 diterpenoid alkaloid derivatives with NSAIDs, organized into four series. Among these derivatives, lappaconitine derivative 1e demonstrated the strongest inhibition of lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells with minimal cytotoxicity. Additionally, 1e effectively suppressed the inflammatory response induced by carrageenan in vivo, with a swelling rate of only 1%. This anti-inflammatory potency was found to be significantly superior to that of naproxen. The molecular docking analysis revealed that the binding affinity of 1e was scored as -10.3 kcal/mol, suggesting that it forms a stable complex with cyclooxygenase-2 (COX-2). Therefore, compound 1e holds potential as a lead anti-inflammatory compound that could be further developed.

Knowledge, attitudes, and practice preferences in the surgical threshold for ascending aortic aneurysm among Canadian cardiac surgeons.

OBJECTIVE: The survey aimed to assess the practice patterns of Canadian cardiac surgeons on the size threshold at which patients with ascending aortic aneurysm would be offered surgery. METHODS: A 18-question electronic survey was electronically distributed to 148 practicing cardiac surgeons in Canada via email from January to August 2020. Questions presented clinical scenarios focusing on modifying a single variable, and respondents were asked to identify their surgical size threshold for each of the clinical scenarios. RESULTS: The individual response rate was 62.0% (91/148) and institutional response rate was 89.3% (25/29). For an incidental asymptomatic ascending aortic aneurysm in a 60-year-old otherwise-healthy male patient with a tricuspid aortic valve and bicuspid aortic valve of 1.9 m2, 20.2% of the respondents would recommend surgery when the aneurysm was <5.5 cm. A significant number of surgeons modified their surgical threshold in response to changes to BSA, bicuspid aortic valve, growth rate, age, occupation, symptom, and family history (P < .01). Notably, if the patient had a bicuspid aortic valve, 41.0% of respondents lowered their threshold for surgery, with only 43.0% recommending surgery at ≥5.5 cm (P < .01). CONCLUSIONS: Practice variations exist in the current size threshold for surgery of ascending aortic aneurysms in Canada. These differences between surgeons are further accentuated in the context of bicuspid aortic valve, smaller body stature, younger age, low growth rate, family history, and for the performance of isometric exercise. These represent important areas where future prospective studies are required to inform best practice.

Risk score for arch reconstruction under circulatory arrest with hypothermia: The ARCH score.

OBJECTIVE: Currently, there is no risk scores built to predict risk in thoracic aortic surgery. This study aims to develop and internally validate a risk prediction score for patients who require arch reconstruction with hypothermic circulatory arrest. METHODS: From 2002 to 2018, data for 2270 patients who underwent aortic arch surgery in 12 institutions in Canada were retrospectively collected. The outcomes modeled included in-hospital mortality and a modified Society of Thoracic Surgeons-defined composite for mortality or major morbidity. Multivariable logistic regression using least absolute shrinkage and selection operator selection method and mixed-effect regression model was used to select the predictors. Internal calibration of the final models is presented with an observed-versus-predicted plot. RESULTS: There were 182 in-hospital deaths (8.0%), and the incidence of Society of Thoracic Surgeons-defined composite for mortality or major morbidity was 27.9%. Variables that increased risk of mortality are age, chronic obstructive pulmonary disease, atrial fibrillation, peripheral vascular disease, New York Heart Association class ≥III symptoms, acute aortic dissection or rupture, use of elephant trunk, concomitant surgery, and increased cardiopulmonary bypass time, with median c-statistics of 0.85 on internal validation. The c-statistics was 0.77 for the model predicting Society of Thoracic Surgeons-defined composite. Internal assessment shows good overall calibration for both models. CONCLUSIONS: We developed and internally validated a risk score for patients undergoing arch surgery requiring hypothermic circulatory arrest using a multicenter database. Once externally validated, the ARCH (Arch Reconstruction under Circulatory arrest with Hypothermia) score would allow for better patient risk-stratification and aid in the decision-making process for surgeons and patient prior to surgery.

Influence of preoperative frailty on quality of life after cardiac surgery: Protocol for a systematic review and meta-analysis.

BACKGROUND: Frailty has emerged as an important prognostic marker of adverse outcomes after cardiac surgery, but evidence regarding its ability to predict quality of life after cardiac surgery is currently lacking. Whether frail patients derive the same quality of life benefit after cardiac surgery as patients without frailty remains unclear. METHODS: This systematic review will include interventional studies (RCT and others) and observational studies evaluating the effect of preoperative frailty on quality-of-life outcomes after cardiac surgery amongst patients 65 years and older. Studies will be retrieved from major databases including the Cochrane Central Register of Controlled Trials, Embase, and Medline. The primary exposure will be frailty status, independent of the tool used. The primary outcome will be change in quality of life, independent of the tool used. Secondary outcomes will include readmission during the year following the index intervention, discharge to a long-term care facility and living in a long-term care facility at one year. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Meta-analysis based on the random-effects model will be conducted to compare the outcomes between frail and non-frail patients. The evidential quality of the findings will be assessed with the GRADE profiler. CONCLUSION: The findings of this systematic review will be important to clinicians, patients and health policy-makers regarding the use of preoperative frailty as a screening and assessment tool before cardiac surgery. STUDY REGISTRATION: OSF registries (https://osf.io/vm2p8).

Preoperative left ventricular end-systolic dimension predicts occurrence of aortic insufficiency following aortic valve preservation and repair surgery.

BACKGROUND: Preoperative left ventricular (LV) end-systolic dimension (LVESD) ≥5.0 cm is a class IIa indication for surgical intervention for aortic insufficiency (AI); however, the effect of LV dilatation on the longevity of the aortic valve (AV) has not yet been investigated. This study aimed to assess the impact of preoperative LV dimension on the long-term outcome of AV preservation surgery. METHODS: Between 2009 and 2019, 256 patients underwent AV preservation surgery at a single center. The median duration of follow-up was 5 years. The primary outcome was the development of >1+ AI at 6 years; secondary outcomes include long-term mortality, freedom from >2+ AI, and freedom from AV reoperation. Cox proportional hazard analysis was performed to identify predictors of AV deterioration. RESULTS: In-hospital mortality was 0.8%, and mean survival at 8 years was 85.5 ± 3.4%. Mean freedom from >1+ AI at 6 years was 71.1 ± 3.4%. Patients with preoperative indexed LVESD (LVESDi) ≥2.0 cm/m2 were at greater risk of developing >1+ AI at 6 years compared with patients with preoperative LVESDi of 1.5 to 1.9 cm/m2 and ≤1.4 cm/m2 (50.3 ± 0.1% vs 80.9 ± 0.1% vs 92.2 ± 0.1%, respectively; P < .01). On risk-adjusted multivariable analysis, preoperative LVESDi was an independent predictor for recurrence of >1+ AI (hazard ratio, 2.2; 95% confidence interval, 1.5-3.4). CONCLUSIONS: Preoperative LVESDi ≥2 cm/m2 is associated with increased risk of recurrent >1+ AI following AV preservation surgery. Further investigation of the appropriate operative threshold for AI may be warranted.

Protocol for a randomised controlled trial for Treatment in Thoracic Aortic Aneurysm: Surgery versus Surveillance (TITAN: SvS).

INTRODUCTION: Ascending thoracic aortic aneurysm (ATAA) is an asymptomatic condition that can lead to catastrophic events of rupture or dissection. Current guidelines are based on limited retrospective data and recommend surgical intervention for ATAA with a diameter of greater or equal to 5.5 cm. Treatment in Thoracic Aortic Aneurysm: Surgery versus Surveillance is the first prospective, multicentre, randomised controlled trial that compares outcomes of patients undergoing early elective ascending aortic surgery to patients undergoing medical surveillance. METHODS AND ANALYSIS: Patients between the ages of 18 and 80 with an asymptomatic ATAA between 5.0 cm and 5.4 cm in diameter are eligible for randomisation to early surgery or surveillance. Patients in the surgery group will be followed at 1 month after discharge, then annually for a minimum of 2 years and up to 5 years. Patients in the surveillance group will be followed annually from their index clinic visit for a minimum of 2 years and up to 5 years. The primary outcome is all-cause mortality at follow-up. A sample size of 618 subjects (309 in each group) will achieve an 80% power at a 0.047 significance level. ETHICS AND DISSEMINATION: This study has received Ottawa Health Science Network Research Ethics Board approval (Protocol 20180007-01H), which was most recently updated on 25 November 2020. The Research Ethics Board have granted approval to the study at 14 participating institutions, including the Ottawa Health Science Network Research Ethics Board. On completion of data analysis, the result of the trial will be presented at national and international conferences, and published in relevant journals, regardless of the finding of the trial. TRIAL REGISTRATION NUMBER: NCT03536312.

Changes and significance of Treg and Th17 in adult patients with primary membranous nephropathy.

OBJECTIVE: To investigate the changes in Treg and Th17 cells and explore the significance of Treg/Th17 balance in adult primary membranous nephropathy (PMN) patients. MATERIALS AND METHODS: A total of 60 PMN patients and 50 healthy adults from June 2013 to October 2016 were enrolled in this study. The levels of Treg, Th17, and related cytokines were assessed. Pearson correlation was used for conducting correlation analysis. RESULTS: There was a significant increase in Th17 frequencies and IL-17 (Th17-related cytokines) in the peripheral blood mononuclear cells (PBMCs), as well as a significant decrease in Treg frequencies and IL-10 (Treg-related cytokines). The IL-17 concentrations in the peripheral blood of PMN patients were positively correlated with urinary protein, while IL-10 levels were negatively correlated with urinary protein. Protein expression of Treg transcription factor (Foxp3) was significantly low in the renal tissues of PMN patients, while the expression of IL-17 was much higher. Th17/Treg imbalance was reversed to normal after effective treatment with tacrolimus in 15 PMN patients. CONCLUSION: These results suggested the existence of Treg/Th17 imbalance in PMN patients, showing the importance of Treg/Th17 imbalance in PMN pathogenesis.