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.

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.

Robotic resection of an aortic valve fibroelastoma using a right lateral approach.

BACKGROUND AND AIM OF THE STUDY: Robotic technology provides excellent visualization and surgical precision and it is reaching maturity in cardiac surgery, although mostly confined to mitral surgery and coronary revascularization. Robotic aortic valve surgery (rAVS) has not been sufficiently developed, and experience is extremely scarce. METHODS: We present a robotic resection of a papillary fibroelastoma on the aortic valve using a totally thoracoscopic right lateral approach. RESULTS: This technique provides excellent exposure, facilitates patient recovery and improves cosmesis. CONCLUSIONS: rAVS has tremendous potential and many patients may benefit in the future. The lateral approach used in our case may offers advantages over others previously attempted and may also facilitate adoption of rAVS by teams currently performing robotic mitral surgery.

Effect of pulmonary artery denervation in postcapillary pulmonary hypertension: results of a randomized controlled translational study.

There is scarce evidence for pulmonary artery denervation (PADN) as a potential treatment for chronic postcapillary pulmonary hypertension (PH). We aimed to perform a proof-of-concept of PADN in a translational model of chronic PH. Nineteen pigs with chronic postcapillary PH (secondary to pulmonary vein banding) were randomized to surgical-PADN (using bipolar radiofrequency clamps) or sham procedure. Additionally, 6 healthy animals underwent percutaneous-PADN to compare the pulmonary artery (PA) lesion generated with both approaches. In the surgical-PADN arm, hemodynamic evaluation and cardiac magnetic resonance (CMR) were performed at baseline and at 2 and 3-month follow-up. Histological assessment was carried out at the completion of the protocol. Eighteen pigs (6 following surgical-PADN, 6 sham and 6 percutaneous-PADN) completed the protocol. A complete transmural PA lesion was demonstrated using surgical clamps, whereas only focal damage to adventitial fibers was observed after percutaneous-PADN. In the surgical-PADN arm, the hemodynamic profile did not significantly differ between groups neither at baseline [mean pulmonary artery pressure (mPAP) median values of 32.0 vs. 27.5 mmHg, P = 0.394 and indexed pulmonary vascular resistance (iPVR) 5.9 vs. 4.7 WU m2, P = 0.394 for PADN/sham groups, respectively] nor at any follow-up (mPAP of 35.0 vs. 35.0 mmHg, P = 0.236 and iPVR of 8.3 vs. 6.7 WU m2, P = 0.477 at third month in PADN/sham groups, respectively). Surgical-PADN was not associated with any benefit in RV anatomy or function on CMR/histology. In a large-animal model of chronic postcapillary PH, transmural PADN with surgical clamps was associated with a neutral pulmonary hemodynamic effect.

Beta-3 adrenergic agonists reduce pulmonary vascular resistance and improve right ventricular performance in a porcine model of chronic pulmonary hypertension.

Beta-3 adrenergic receptor (ß3AR) agonists have been shown to produce vasodilation and prevention of ventricular remodeling in different conditions. Given that these biological functions are critical in pulmonary hypertension (PH), we aimed to demonstrate a beneficial effect of ß3AR agonists in PH. An experimental study in pigs (n = 34) with chronic PH created by pulmonary vein banding was designed to evaluate the acute hemodynamic effect and the long-term effect of ß3AR agonists on hemodynamics, vascular remodeling and RV performance in chronic PH. Ex vivo human experiments were performed to explore the expression of ß3AR mRNA and the vasodilator response of ß3AR agonists in pulmonary arteries. Single intravenous administration of the ß3AR agonist BRL37344 produced a significant acute reduction in PVR, and two-weeks treatment with two different ß3AR selective agonists, intravenous BRL37344 or oral mirabegron, resulted in a significant reduction in PVR (median of -2.0 Wood units/m(2) for BRL37344 vs. +1.5 for vehicle, p = 0.04; and -1.8 Wood units/m(2) for mirabegron vs. +1.6 for vehicle, p = 0.002) associated with a significant improvement in magnetic resonance-measured RV performance. Histological markers of pulmonary vascular proliferation (p27 and Ki67) were significantly attenuated in ß3AR agonists-treated pigs. ß3AR was expressed in human pulmonary arteries and ß3AR agonists produced vasodilatation. ß3AR agonists produced a significant reduction in PVR and improved RV performance in experimental PH, emerging as a potential novel approach for treating patients with chronic PH.

[Surgery in the Cardiovascular Surgical Intensive Care Unit]. / Reintervenciones en una Unidad de Cuidados Intensivos de Cirugía Cardiovascular.

BACKGROUND: To analyze the indications, actions and results of the operations performed in the Cardiovascular Surgery Intensive Care Unit. METHODS: Retrospective analysis of consecutive non-selected adult patients operated in the ICU. All operations were included. Descriptive statistics were used. RESULTS: Between 2008 and 2013, 3379 consecutive adult patients were operated upon. A total of 124 operations were performed in the ICU in 109 patients, 70 male (64.2%) and 39 female (35.8%) with a mean age of 61.6 years (12-80). This represented 3.2% of all operations. During the study period, 185 patients (5.5%) were reoperated for postoperative bleeding/tamponade in the operating room. The index interventions were for valvular heart disease (34.9%), aortic disease (22.9%), ischemic heart disease (15.6%), combined valvular/ischemic (12%), valvular/aorta (11%) and miscellaneous (3.6%). The indications for reoperation were persistent bleeding 54 (43.5%), pericardial tamponade 41 (33%), low cardiac output 13 (10.5%), cardiac arrest/arrhythmia 8 (6.5%), respiratory insufficiency 6 (4.8%) and acute ischemic limb 2 (1.7%). Operations performed were: mediastinal exploration 73 (58.9%), implant/removal of ECMO 17 (13.7%), sternal closure 16 (12.9%), open resuscitation 9 (7.3%), subxyphoid drainage 7 (5.6%) and femoral embolectomy 2 (1.6%). Overall mortality was 33%. There was one case of mediastinitis (0,9%), with no difference from patients operated in the regular operating room. CONCLUSIONS: Operations in the ICU represent a safe, life-saving alternative in specific subgroups of patients. The risk of wound infection is not increased, unstable patients are not transferred and there is time savings.

Characterization of right ventricular remodeling and failure in a chronic pulmonary hypertension model.

In pulmonary hypertension (PH), right ventricular (RV) dysfunction and failure is the main determinant of a poor prognosis. We aimed to characterize RV structural and functional differences during adaptive RV remodeling and progression to RV failure in a large animal model of chronic PH. Postcapillary PH was created surgically in swine (n = 21). After an 8- to 14-wk follow-up, two groups were identified based on the development of overt heart failure (HF): PH-NF (nonfailing, n = 12) and PH-HF (n = 8). In both groups, invasive hemodynamics, pressure-volume relationships, and echocardiography confirmed a significant increase in pulmonary pressures and vascular resistance consistent with PH. Histological analysis also demonstrated distal pulmonary arterial (PA) remodeling in both groups. Diastolic dysfunction, defined by a steeper RV end-diastolic pressure-volume relationship and longitudinal strain, was found in the absence of HF as an early marker of RV remodeling. RV contractility was increased in both groups, and RV-PA coupling was preserved in PH-NF animals but impaired in the PH-HF group. RV hypertrophy was present in PH-HF, although there was evidence of increased RV fibrosis in both PH groups. In the PH-HF group, RV sarcoplasmic reticulum Ca(2+)-ATPase2a expression was decreased, and endoplasmic reticulum stress was increased. Aldosterone levels were also elevated in PH-HF. Thus, in the swine pulmonary vein banding model of chronic postcapillary PH, RV remodeling occurs at the structural, histological, and molecular level. Diastolic dysfunction and fibrosis are present in adaptive RV remodeling, whereas the onset of RV failure is associated with RV-PA uncoupling, defective calcium handling, and hyperaldosteronism.

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.

Hamartoma of Mature Cardiac Myocytes presenting as a polypoid epicardial tumor in the interatrial groove and with gene fusions by copy number anomalies of chromosome 7.

Hamartoma of Mature Cardiac Myocytes (HMCM) is an extremely rare cardiac tumor characterized by benign growth of differentiated mature striated cardiac myocytes, and usually involves the ventricular myocardium. We describe the case of a 15-year-old female who presented with a short history of atrial fibrillation and a polypoid epicardial tumor that was attached to the interatrial groove by a short pedicle. The resected specimen showed features consistent with HMCM. Although these tumors are not associated with any known molecular or cytogenetic abnormalities, we identified fusions transcripts along with complex copy number anomalies of chromosome 7.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.