Five-year results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement-the ARISE Study and ARISE Registry Data.

OBJECTIVES: Decellularized aortic homografts (DAH) were introduced as a new option for aortic valve replacement for young patients. METHODS: A prospective, EU-funded, single-arm, multicentre study in 8 centres evaluating non-cryopreserved DAH for aortic valve replacement. RESULTS: A total of 144 patients (99 male) were prospectively enrolled in the ARISE Trial between October 2015 and October 2018 with a median age of 30.4 years [interquartile range (IQR) 15.9-55.1]; 45% had undergone previous cardiac operations, with 19% having 2 or more previous procedures. The mean implanted DAH diameter was 22.6 mm (standard deviation 2.4). The median operation duration was 312 min (IQR 234-417), the median cardiopulmonary bypass time was 154 min (IQR 118-212) and the median cross-clamp time 121 min (IQR 93-150). No postoperative bypass grafting or renal replacement therapy were required. Two early deaths occurred, 1 due to a LCA thrombus on day 3 and 1 due ventricular arrhythmia 5 h postoperation. There were 3 late deaths, 1 death due to endocarditis 4 months postoperatively and 2 unrelated deaths after 5 and 7 years due to cancer and Morbus Wegener resulting in a total mortality of 3.47%. After a median follow-up of 5.9 years [IQR 5.1-6.4, mean 5.5 years. (standard deviation 1.3) max. 7.6 years], the primary efficacy end-points peak gradient with median 11.0 mmHg (IQR 7.8-17.6) and regurgitation of median 0.5 (IQR 0-0.5) of grade 0-3 were excellent. At 5 years, freedom from death/reoperation/endocarditis/bleeding/thromboembolism were 97.9%/93.5%/96.4%/99.2%/99.3%, respectively. CONCLUSIONS: The 5-year results of the prospective multicentre ARISE trial continue to show DAH to be safe for aortic valve replacement with excellent haemodynamics.

Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation.

Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine-histidine-purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH.

Minimally Invasive Mitral Valve Repair: From Total Endoscopic To Closed-Chest Robotic.

Minimally invasive cardiac surgery has evolved over the past few decades, thanks to advancements in technology and surgical techniques. These advancements have allowed surgeons to perform cardiac interventions through small incisions, reducing surgical trauma and improving patient outcomes1. However, despite these advancements, thoracoscopic mitral repair has not been widely adopted by the cardiac surgery community, possibly due to the lack of familiarity with video-assisted procedures1. Over the years, various minimally invasive mitral valve surgery (MIMVS) techniques have been developed to achieve comparable or better results while minimizing surgical trauma. These techniques have evolved from direct-vision procedures performed through a right thoracotomy with a rib retractor to video-directed approaches using long-shafted instruments1. Robotic surgery, introduced in the late 90s, has also played a significant role in mitral valve repair. The da Vinci system, the only robotic platform currently used for cardiac surgery, provides surgeons with enhanced dexterity and high-definition 3D visualization, allowing for precise and accurate procedure2, and is now the preferred approach for mitral repair in many programs3. The first mitral repair using the da Vinci system was performed in Europe by Carpentier and Mohr in 1998, followed by the first mitral replacement by Chitwood in the USA in 20002-4. The advantages of robotic technology allow surgeons to perform complex repair techniques such as papillary muscle repositioning and sliding leaflet plasty4. Studies have shown that robotic mitral surgery results in shorter ICU and hospital stays, better quality of life postoperatively, and improved cosmesis compared to conventional surgery5,6. In our experience, we have also observed significant benefits with robotic surgery, including reduced blood loss and the need for transfusions. This can be attributed to the closed-chest technique, which eliminates the need for a thoracotomy and rib retractor, reducing the risk of bleeding associated with these approaches7. In this article, we will compare the surgical steps of endoscopic and robotic mitral valve repair, providing detailed information on patient selection, operative techniques, and the requirements for building a successful program. By understanding the advantages and challenges of both approaches, surgeons can make informed decisions and provide the best possible care for their patients. Combined ablation and multivalvular procedures are mostly performed in few centers by minimally invasive techniques.

Closed-chest robotic repair of mitral prolapse. Surgical technique and early results.

Background: Robotic mitral repair is generally performed with four intercostal trocars and a minithoracotomy. We describe our technique and results with a totally-thoracoscopic closed chest approach using a 12 mm valveless trocar as "working port", without a minithoracotomy. We compared our results with this technique with a control group of robotic mitral repairs performed earlier with a minithoracotomy. Methods: Review of all patients with degenerative mitral valve disease who underwent robotic mitral valve repair surgery since December 2019 (n = 110). Patients with concomitant procedures (n = 8) were excluded. The remaining 102 patients were divided in two groups, depending on the approach used, minithoracotomy (n = 63) and totally thoracoscopic (n = 39). Results: There were no significant differences between groups regarding preoperative characteristics. All procedures were completed robotically as planned, and repair rate was 100%. The minithoracotomy group showed a higher percentage of leaflet resections (17.9% vs. 38.7%; p = 0.03). All surgical times were significatively reduced in the totally thoracoscopic group: Cardiopulmonary bypass (97 vs. 115 min, p = 0.0008), ischemic time (67 vs. 80 min, p = 0.0013) and total surgical time (185 vs. 225 min; p < 0.00001). There were no differences in ICU length of stay (1 day, p = 0.07) but hospital length of stay was shorter in the totally thoracoscopic group (4 days; p = 0.0001). Postoperative complications were similar between groups. MR at discharge was mild or less in all cases. Conclusions: Robotic mitral repair for degenerative disease can be safely performed as a closed-chest procedure, using a 12 mm trocar as "working port" and avoiding the need for a minithoracotomy. This approach does not seem to negatively affect the quality of the procedure by any measure, providing similar excellent clinical outcomes and repair rate. All surgical times were shorter in the closed-chest group.

The impact of annuloplasty ring or band implantation on post-repair mitral valve haemodynamic performance.

OBJECTIVES: The clinical importance of optimal post-repair mitral valve diastolic performance is increasingly being recognized. The haemodynamic effect of a partial annuloplasty band implantation, in comparison to a full ring, remains insufficiently explored. METHODS: Patients undergoing mitral valve repair for pure degenerative disease between 2011 and 2019 at 2 experienced heart valve centres were eligible for inclusion. Exclusion criteria were concomitant procedures other than tricuspid valve repair and ablation procedures for atrial fibrillation. Pre-discharge and follow-up echocardiograms (1-4 years after surgery) were analysed to assess haemodynamic mitral valve performance. RESULTS: Of 535 patients meeting the inclusion criteria, 364 (68.0%) patients underwent full annuloplasty ring and 171 (31.0%) partial band implantation. On predischarge echocardiogram, post-repair mitral valve gradient and area did not differ between groups [2.89 mmHg (IQR 2.26-3.72) vs 2.60 mmHg (IQR 1.91-3.55), P = 0.19 and 1.98 cm2 (IQR 1.66-2.46) vs 2.03 cm2 (IQR 1.55-3.06), P = 0.15]. However, multivariable linear regression analysis demonstrated band annuloplasty as a determinant of larger valve area (coefficient 0.467 cm2, standard error 0.105, P < 0.001). On multivariable analysis, no significant impact on post-repair gradient was observed (-0.370 mmHg, standard error 0.167, P = 0.36). At follow-up, the differences between groups disappeared and multivariable regression analysis failed to demonstrate a significant impact of annuloplasty device type on mitral valve gradient (coefficient -0.095 mmHg, standard error 0.171, P = 1.00) or area (coefficient -0.085 cm2, standard error 0.120, P = 1.00). These results were confirmed with a linear mixed model analysis. CONCLUSIONS: Partial band annuloplasty was related to an improved haemodynamic profile directly after valve repair for degenerative disease but the effect was short-lived. Our results suggest that the type of annuloplasty device has no durable impact on diastolic valve performance.

Commando procedure with posterior atrioventricular groove reconstruction.

This case presents a Commando procedure with posterior atrioventricular groove reconstruction in a patient after double-valve replacement performed in another hospital with a posterior atrioventricular groove patch due to mitral annular calcification for aortomitral Streptococcus agalactiae endocarditis. The patient was transferred to our institution on postoperative day 6 under femoro-axillary venoarterial extracorporeal membrane oxygenation with cardiogenic shock and pulmonary oedema due to patch dehiscence and severe periprosthetic mitral leak. To control pulmonary oedema and decrease myocardial tension, left atrial venting was performed in the intensive care unit through a redo sternotomy. After 24 hours, repeat reconstruction surgery was performed after improvement of pulmonary infiltrates and contractility. We alternate operative images with a porcine wet-lab model to facilitate understanding of this advanced reconstruction.

Repair of mitral prolapse: comparison of thoracoscopic minimally invasive and conventional approaches.

OBJECTIVES: Surgical repair remains the best treatment for severe primary mitral regurgitation (MR). Minimally invasive mitral valve surgery is being increasingly performed, but there is a lack of solid evidence comparing thoracoscopic with conventional surgery. Our objective was to compare outcomes of both approaches for repair of leaflet prolapse. METHODS: All consecutive patients undergoing surgery for severe MR due to mitral prolapse from 2012 to 2020 were evaluated according to the approach used. Freedom from mortality, reoperation and recurrent severe MR were evaluated by Kaplan-Meier method. Differences in baseline characteristics were adjusted with propensity score-matched analysis (1:1, nearest neighbour). RESULTS: Three hundred patients met inclusion criteria and were divided into thoracoscopic (N = 188) and conventional (sternotomy; N = 112) groups. Unmatched patients in the thoracoscopic group were younger and had lower body mass index, New York Heart Association class and EuroSCORE II preoperatively. After matching, thoracoscopic group presented significantly shorter mechanical ventilation (9 vs 15 h), shorter intensive care unit stay (41 vs 65 h) and higher postoperative haemoglobin levels (11 vs 10.2 mg/dl) despite longer bypass and cross-clamp times (+30 and +17 min). There were no differences in mortality or MR grade at discharge between groups nor differences in survival, repair failures and reinterventions during follow-up. CONCLUSIONS: Minimally invasive mitral repair can be performed in the majority of patients with mitral prolapse, without compromising outcomes, repair rate or durability, while providing shorter mechanical ventilation and intensive care unit stay and less blood loss.

Does Quality of Life in Survivors of Surgery for Acute Left-Sided Infective Endocarditis Differ from Non-Endocarditis Patients?

Surgery for left-sided infective endocarditis (IE) has been demonstrated to improve patients' survival rates but information about quality of life (QoL) after surgery is scarce. The aim of this study was to assess the postoperative outcomes and QoL after surgery for IE patients compared to patients undergoing cardiac surgery for non-IE indications. Adult patients with definite acute left-sided IE were matched 1:1 to patients who underwent cardiac surgery for non-endocarditic purposes from 2014 to 2019. QoL was assessed using the SF-36 survey at the last follow-up. A total of 105 patients were matched. The IE group had higher rates of preoperative stroke (21% vs. 7.6%, p = 0.005) and higher stages of NYHA class (p < 0.001), EuroSCORE II (12.3 vs. 3.0, p < 0.001) and blood cell count abnormalities (p < 0.001). The IE group had higher incidence of low cardiac output syndrome (13.3% vs. 4.8%, p = 0.029), dialysis (10.5% vs 1.0%, p = 0.007) and prolonged mechanical ventilation (16.2% vs. 2.9%, p = 0.002) after surgery. At the last follow-up, subcomponents of the SF-36 QoL survey were not different between the groups. Patients who underwent cardiac surgery for IE demonstrated a higher risk profile with a higher rate of postoperative complications. Once recovered from the acute phase of the disease, the reported QoL at follow-up was comparable to that of matched cardiac patients operated for non-IE purposes.

ß3 adrenergic agonist treatment in chronic pulmonary hypertension associated with heart failure (SPHERE-HF): a double blind, placebo-controlled, randomized clinical trial.

AIMS: Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre- and post-capillary PH combine. The current study aimed to determine whether treatment with the selective ß3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre- and post-capillary PH (CpcPH). METHODS AND RESULTS: The ß3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE-HF) trial is a multicentre, randomized, parallel, placebo-controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n = 39) or placebo (n = 41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo-corrected mean difference of 0.62 Wood units, 95% confidence interval [CI] -0.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo-corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre-specified secondary outcomes. CONCLUSIONS: SPHERE-HF is the first clinical trial to assess the potential benefit of ß3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre-specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.

Simulation-based assessment of robotic cardiac surgery skills: An international multicenter, cross-specialty trial.

Objective: This study aimed to investigate the validity of simulation-based assessment of robotic-assisted cardiac surgery skills using a wet lab model, focusing on the use of a time-based score (TBS) and modified Global Evaluative Assessment of Robotic Skills (mGEARS) score. Methods: We tested 3 wet lab tasks (atrial closure, mitral annular stitches, and internal thoracic artery [ITA] dissection) with both experienced robotic cardiac surgeons and novices from multiple European centers. The tasks were assessed using 2 tools: TBS and mGEARS score. Reliability, internal consistency, and the ability to discriminate between different levels of competence were evaluated. Results: The results demonstrated a high internal consistency for all 3 tasks using mGEARS assessment tool. The mGEARS score and TBS could reliably discriminate between different levels of competence for the atrial closure and mitral stitches tasks but not for the ITA harvesting task. A generalizability study also revealed that it was feasible to assess competency of the atrial closure and mitral stitches tasks using mGEARS but not the ITA dissection task. Pass/fail scores were established for each task using both TBS and mGEARS assessment tools. Conclusions: The study provides sufficient evidence for using TBS and mGEARS scores in evaluating robotic-assisted cardiac surgery skills in wet lab settings for intracardiac tasks. Combining both assessment tools enhances the evaluation of proficiency in robotic cardiac surgery, paving the way for standardized, evidence-based preclinical training and credentialing. Clinical trial registry number: NCT05043064.

Robotic Aortic Valve Replacement Using the Intuity Bioprosthesis Through a Right Lateral Approach.

Robotic technology offers excellent visualization and surgical precision but has not been established for aortic valve surgery. We present the first 2 cases of patients with severe aortic stenosis who underwent successful robotic aortic valve replacement using a lateral approach and the Edwards Intuity® rapid-deployment bioprosthesis. Postoperative recovery was excellent, and both patients were discharged home on the fourth postoperative day. We believe this approach is valuable for robotic aortic valve replacement and may help to finally bridge the gap into routine clinical use, becoming a valuable option for the surgical treatment of the aortic valve in selected patients.

Effects of Dietary n-3 LCPUFA Supplementation on the Hippocampus of Aging Female Mice: Impact on Memory, Lipid Raft-Associated Glutamatergic Receptors and Neuroinflammation.

Long-chain polyunsaturated fatty acids (LCPUFA), essential molecules whose precursors must be dietary supplied, are highly represented in the brain contributing to numerous neuronal processes. Recent findings have demonstrated that LCPUFA are represented in lipid raft microstructures, where they favor molecular interactions of signaling complexes underlying neuronal functionality. During aging, the brain lipid composition changes affecting the lipid rafts' integrity and protein signaling, which may induce memory detriment. We investigated the effect of a n-3 LCPUFA-enriched diet on the cognitive function of 6- and 15-months-old female mice. Likewise, we explored the impact of dietary n-3 LCPUFAs on hippocampal lipid rafts, and their potential correlation with aging-induced neuroinflammation. Our results demonstrate that n-3 LCPUFA supplementation improves spatial and recognition memory and restores the expression of glutamate and estrogen receptors in the hippocampal lipid rafts of aged mice to similar profiles than young ones. Additionally, the n-3 LCPUFA-enriched diet stabilized the lipid composition of the old mice's hippocampal lipid rafts to the levels of young ones and reduced the aged-induced neuroinflammatory markers. Hence, we propose that n-3 LCPUFA supplementation leads to beneficial cognitive performance by "rejuvenating" the lipid raft microenvironment that stabilizes the integrity and interactions of memory protein players embedded in these microdomains.

Intraoperative Collateral Drainage Evaluation Before Superior Caval Interruption in Partial Anomalous Pulmonary Venous Connection Repair.

A superior sinus venosus atrial septal defect and partial anomalous pulmonary venous connection was corrected by a minimally invasive approach by permanently ligating the superior vena cava and a single pericardial patch for rerouting the flow through the enlarged interatrial communication. The patient had persistency of the left superior vena cava draining in the coronary sinus but no innominate vein. This anatomy poses a risk of developing right-sided superior vena cava syndrome. In this article, we describe our intraoperative strategy to assess the safety of this approach in such cases, which facilitates minimally invasive repair and avoids the most important complications of conventional repair.