Evolution of Minimally Invasive Mitral Valve Repair: 30-Year Experience From a High-Volume Center

Background: Minimally invasive mitral valve repair (MVr) is a reproducible, widely adopted, and routinely performed surgical procedure. It is often performed in combination with tricuspid valve (TV) surgery. However, evidence on long-term results and their evolution over time is limited. This study evaluated whether outcomes of isolated minimally invasive MVr or minimally invasive MVr with concomitant TV surgery have improved over the last decades.

Methods: All patients undergoing minimally invasive MVr between 1996 and 2023 were included and split into 5 periods depending on the year of surgery (period 1, 1996-2001; period 2, 2002-2007; period 3, 2008-2013; period 4, 2014-2019; period 5, 2020-2023). The primary study outcome was 10-year survival during different periods. A subanalysis was performed for patients undergoing concomitant TV surgery.

Results: A total of 5559 patients with a median age of 59 years (interquartile range, 50-68 years) were included. Among them, 66.0% (n = 3217) of these patients were male, and 12.4% (n = 687) underwent combined MVr and TV surgery. The 30-day mortality steadily improved, ranging from 0.3% in period 5 to 1.1% in period 1. The 10-year estimated survival ranged from 68.1% in period 1 to 83.7% in period 4 (log-rank P < .0001). The estimated 1- and 10-year survival in patients with concomitant TV surgery steadily improved, with the lowest survival in period 1 (1-year, 62.3%; 10-year, 8.9%) and the highest survival in period 4 (1-year, 92.5%; 10-year, 62.7%).

Conclusions: Minimally invasive MVr surgery, isolated or in combination with TV surgery, is a safe and reproducible surgical approach with low complication rates, infrequent conversion to sternotomy, and excellent early and long-term survival.

Cryopreserved vs Liquid-Stored Platelets for the Treatment of Surgical Bleeding: The CLIP-II Randomized Noninferiority Clinical Trial

Importance: Liquid-stored platelets have a shelf-life of 5 to 7 days, limiting availability and resulting in wastage.

Objective: To assess the effectiveness and safety of dimethyl sulfoxide-cryopreserved platelets, which have a shelf-life of 2 years, as a treatment for cardiac surgery bleeding.

Design, setting, and participants: The Cryopreserved vs Liquid Platelets II (CLIP-II) trial was a multicenter, randomized, double-blind, parallel-group noninferiority trial, which enrolled patients between August 2021 and April 2024 at 11 Australian tertiary hospitals, with follow-up completed in July 2024. Patients at high risk of platelet transfusion were eligible. Patients were excluded if they had a history of deep vein thrombosis or pulmonary embolism, were coagulopathic, or were females aged 18 to 55 years who were rhesus D (RhD) negative or of unknown RhD status. Of 879 patients meeting inclusion criteria, 182 were excluded and 285 did not consent, leaving 412. Of these, 388 were randomized and 202 received study platelets.

Interventions: Patients received up to 3 units of either group O cryopreserved platelets or conventional liquid-stored platelets, commencing intraoperatively or in the first 24 postoperative hours.

Main outcomes and measures: The primary outcome was postsurgical chest drain bleeding within the first 24 hours following intensive care unit admission. Noninferiority was defined prospectively as less than 20% greater bleeding in this period. Five secondary and 42 tertiary outcomes were defined a priori.

Results: Of the 202 transfused patients (mean [SD] age, 64.4 [13] years; 75.7% male), 61 (30.2%) underwent nonelective surgery. The primary outcome did not differ between groups (605 mL in cryopreserved platelet group vs 535 mL in liquid-stored platelet group; ratio of geometric means [cryopreserved to liquid ratio], 1.13 [95% CI, 0.96-1.34]; P = .07). As the confidence interval includes bleeding exceeding the noninferiority margin, noninferiority was not established. Cryopreserved platelet transfusion was associated with higher intraoperative and total perioperative blood loss (ratio of geometric means [cryopreserved to liquid ratio], 1.42 [95% CI, 1.12-1.80]; 1.31 [95% CI, 1.07-1.60], respectively), and increased red cell, plasma, and cryoprecipitate transfusion. While there were no differences in the incidence of prespecified adverse events, patients receiving cryopreserved platelets experienced longer times to extubation and intensive care unit/hospital discharge (median [IQR] duration of ventilation, 25.5 hours [16.1-77.3] vs 23.6 hours [13.1-52.8]; median [IQR] intensive care unit length of stay, 3.8 days [2.0-6.0] vs 3.0 days [1.9-4.9]; median hospital length of stay, 10.9 days [7.87-17.0] vs 9.1 [6.9-14.9]).

Conclusions and relevance: Cryopreserved platelets did not meet the predefined threshold for noninferiority in hemostatic effectiveness at 24 hours after ICU admission. Additional predefined end points consistently indicated diminished hemostatic effectiveness, although prespecified adverse events were comparable.

Mitral valve surgery in mitral annular calcification

Mitral annular calcification (MAC) remains a challenging pathology in the context of mitral valve disease. It is associated with known cardiovascular risk factors, as well as a variety of chronic inflammatory, infective, or connective tissue diseases. Surgically, patients are at specific operative risk for atrioventricular dehiscence or rupture and/or injury to the circumflex artery. To mitigate these risks, a broad portfolio of surgical options exists to safely anchor annular sutures. This can be performed after the calcium bar has been removed and the posterior annulus reconstructed with a patch, or even when the calcium bar is left in place. Knowledge of these techniques will help surgeons manage MAC and implant a properly sized valve. Even in the presence of severe MAC with additional involvement of the mitral valve leaflets, transatrial transcatheter heart valve (THV) implantation may be a viable option. An individualized decision-making process to determine the applicable technique should be used for patients with MAC, leading to adequate treatment for this high-risk patient group.

Epigenetic Reprogramming via TET2 Prevents Medial Calcification and Restores Vascular Smooth Muscle Cell Identity.

Vascular calcification arises from the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) and is a hallmark of many cardiovascular pathologies. This study identifies Tet2, a DNA demethylase, as a critical epigenetic regulator that prevents this phenotypic switch. VSMC-specific loss of Tet2 promotes osteogenic differentiation, apoptosis, increased infiltration of Trem2hi macrophages and medial aortic calcification. High-dose ascorbate used to enhance Tet2 activity significantly reduced calcification and preserved aortic structure in mice. These findings support Tet2 reactivation as a potential therapeutic strategy to prevent or reverse vascular calcification in cardiovascular disease.

Human Hearts Intrinsically Increase Cardiomyocyte Mitosis After Myocardial Infarction.

Background: Myocardial infarction (MI) is a leading cause of death worldwide and can eliminate up to a third of the cardiomyocytes within the human heart. Although cardiomyocytes undergo mitosis during early development, most cardiomyocytes cease cell cycling soon after birth. In contrast, rodent MI models have shown that cardiomyocytes increase mitosis in response to ischemia; however, this has not been shown in humans.

Methods: Using a unique premortem post-MI human heart, immunostaining, bulk RNA sequencing, proteomics, metabolomics, single-nucleus RNA sequencing and a novel post-MI human biopsy method, we investigated human cardiomyocyte mitosis post-MI.

Results: We show that adult human cardiomyocytes exhibit increased mitosis and cytokinesis in response to ischemia.

Conclusions: Future development of therapeutics to enhance this intrinsic mitotic potential could lead to new treatments that reverse heart failure via cardiac regeneration.

Endoscopic and direct vision approaches in minimally-invasive mitral and tricuspid valve surgery – insights from the mini-mitral registry

Background: We investigated the international mini-mitral registry (MMIR) for differences in minimally-invasive access for surgery on the mitral and tricuspid valve. We compared direct vision with partially or fully endoscopic approaches.

Methods: From 2015 to 2021, 7,513 consecutive patients underwent mini-MVR ± TVR in 17 international Heart-Valve-Centers. Data were collected according to MVARC definitions and 6463 patients undergoing first time mitral with or without tricuspid valve surgery were analyzed. Uni- and multivariable regression analyzes were performed to compare the different approaches.

Results: Patients were 65 years (57% male) and oldest in the direct-vision group (n = 1594). Endoscopes (video-assisted: n = 2850, fully-endoscopic: n = 1963) were used in slightly more selected patients (less obesity, diabetes, dialysis, CAD, pulmonary hypertension, reduced LVEF and urgent status compared to direct vision). Robot was used in 56 cases (most selected, no mortality, not further analyzed). Fully-endoscopically, most cases were repairs, concomitant tricuspid surgery was lowest (13% vs. 20%) and both cardiopulmonary bypass and cross-clamp times were longest (90 min, IQR 71-113 min). Cross-clamp times were shortest in the direct vision group (-20 min). Technical success was high (above 96%), in-hospital mortality and stroke rates low and not significantly different between groups. Low output was highest with direct vision and acute kidney injury highest fully-endoscopically. However, this difference was not significant.

Conclusions: In this large registry, the type of minimally-invasive approach did not significantly affect outcome. It appears that fully endoscopic and robotic cases are used more selectively. Mastering both techniques may optimize patient care.

Surgical techniques and outcomes for atrial functional mitral regurgitation: Insights from the mini mitral international registry

Objective: Evidence on optimal therapeutic strategies for atrial functional mitral regurgitation (AFMR) remains limited. This study aimed to evaluate patient characteristics, surgical techniques, and outcomes in AFMR patients from the Mini Mitral International Registry.

Methods: Patients undergoing mini mitral surgery for AFMR between 2015 and 2023 were identified. Exclusion criteria included organic lesions, abnormal leaflet motion, reduced left ventricular function, absence of annular dilation, and previous mitral procedures.

Results: Of 7,957 patients, 430 (5.4%) met AFMR criteria. The cohort was elderly (median age 73), predominantly female (67.7%), with frequent atrial fibrillation (AF) (69.7%). Mitral repair was performed in 91.4% of patients, all via isolated annuloplasty except 3. Complete rings were used in 97.1%. On multivariable analysis anterior mitral leaflet (AML) pseudo-prolapse was associated with an increased likelihood of valve replacement (OR 5.3, 95%CI 1.07-9.12). Concomitant tricuspid repair, AF ablation, and left atrial appendage closure were performed in 44.2%, 40.5%, and 25.6%, respectively. At discharge, 99% had none or mild regurgitation; in-hospital mortality and stroke were 2.3% and 1.9%.

Conclusions: Findings from the MMIR indicate that mitral repair with isolated annuloplasty was the preferred surgical strategy for AFMR, providing satisfactory procedural and early clinical outcomes. The presence of AML pseudo-prolapse reduced the likelihood of valve repair. Overall operative results were favorable, with 99% of patients experiencing no or mild residual mitral regurgitation. These findings may serve as a reference for clinical decision-making in AFMR treatment pathways.

Association between obstructive sleep apnea and thoracic aortic diameter: a cross-sectional study in a clinical sample

Study objectives: Previous studies have suggested that obstructive sleep apnea (OSA) may be associated with aortic dilatation. We aimed to further characterize the association between OSA severity with thoracic aortic diameter.

Methods: We evaluated 1,470 patients attending an Australian clinic during 2014-2023 and who underwent transthoracic echocardiogram followed by polysomnographic study in the following 6 months (43.7% female, median age 65 years, median body mass index 29.6 kg/m2). Aortic root and ascending aortic diameters were compared among patients based on OSA severity, defined by apnea-hypopnea index.

Results: OSA was observed in 90% of patients. Both aortic root and ascending aorta diameters were associated with increasing OSA severity (P < .01). These associations remained significant when indexed for height, but not body surface area. Multivariate analysis considering age, weight, hypertension status, atrial fibrillation, and smoking history suggested an independent role of OSA on aortic dimensions in females but not in males. However, a case-control sensitivity analysis did not demonstrate a significant difference in aortic diameter between no/mild OSA compared to moderate/severe OSA.

Conclusions: This is the largest study examining the association of OSA and thoracic aortic dimensions in a clinical sample. It found a significant increase in both aortic root and ascending aorta diameters with increasing OSA severity, although this may be explained by shared risk factors such as age, body mass index, hypertension, and atrial fibrillation. A minor independent association between aortic dimensions and OSA severity was observed in females but not males. Further research is warranted to explore the relationship between OSA and aortopathy.

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