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Minimally invasive mitral valve surgery (MIMVS) has become a well-established alternative to traditional median sternotomy at high-volume surgical centers. Advancements in surgical instruments have led to further refinement of MIMVS. However, MIMVS remains limited to select patients in select settings. In this review, we provide a brief overview of the evolution of MIMVS, as well as a technical description of the most relevant aspects of minimally invasive mitral valve surgery.

Background: Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury., Methods: In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.3 or 0.65 mg/kg) or placebo (1:1) for 2 days (5 intravenous infusions), stratified by region and renal function. Eligible patients had at least one pre-defined AKI risk factor. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m 2 ) were excluded. The co-primary efficacy and safety endpoints were AKI (Kidney Disease: Improving Global Outcomes definition) within 72 h after surgery and nature, frequency, and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included eGFR and Major Adverse Kidney Events (MAKE) up to Day 90. Randomised patients who had received at least one dose of study drug were analysed for primary and safety analyses. Participants, investigators and sponsor were masked to treatment allocation. This study is registered at ClinicalTrials.gov (NCT05126303) and EudraCT (2021-004040-19)., Findings: Patient enrolment was stopped at interim analysis due to futility. Between March 31, 2022 and July 12, 2023, 177 patients (RMC-035: 89, placebo: 88) were randomised and treated. AKI rate for RMC-035 vs placebo was 50.6% (n = 45) and 39.8% (n = 35) (relative risk [RR]: 1.30, 90% confidence interval [90% CI]: 0.99, 1.71; p = 0.12). A short-lived creatinine increase was observed with the higher RMC-035 dose. Treatment with RMC-035 was associated with improved secondary renal outcomes at Day 90: placebo-adjusted eGFR change from baseline 4.3 mL/min/1.73 m 2 , 90% CI 0.51-8.12, p = 0.06; and MAKE 6.7% (n = 6) vs 15.9% (n = 14); RR: 0.41, 90% CI: 0.19, 0.88, p = 0.05. The most frequently reported TEAEs for RMC-035 were chills (30.3%), nausea (21.3%), anaemia (20.2%); and atrial fibrillation (29.5%), anaemia (20.5%), hypervolemia (14.8%) for placebo. The majority of TEAEs in both treatment groups were mild or moderate in severity. In the RMC-035 group, 26 (29.2%) patients experienced at least one severe or life-threatening TEAE and in the placebo group 16 (18.2%) patients. There were 4 deaths per treatment arm (one treatment-related, in placebo group)., Interpretation: In this proof-of-concept study, RMC-035 did not reduce AKI 72 h after cardiac surgery. Evaluations may have been confounded by a drug-induced transient creatinine increase in a subgroup of patients. RMC-035 was associated with improved secondary renal outcomes. These results merit further investigation and should be interpreted with caution, as the study was not powered for these outcomes., Funding: Guard Therapeutics., Competing Interests: AZ received consulting and lecture fees and grants from German Research Foundation, BioMerieux, Baxter, Fresenius, Paion, Viatris, Bayer, Novartis, AM Pharma, and Alexion, received meeting and travel support from Sphingotec and held leadership and fiduciary roles at the German Interdisciplinary Association for Intensive and Emergency Medicine, the International Anesthesia Research Society and the journal “Der Anästhesist”. JLK received consulting fees from Biomerieux, Baxter, Alexion, SeaStar, Novartis, Guard Therapeutics and research funding from the NIH, Fresenius Medical and Biomerieux. TEL is a shareholder and employee of Guard Therapeutics. MR holds stock options and is a paid consultant to Guard Therapeutics. CDM received consulting fees from Alexion. AB was past-president of the German society for heart, thorax and vascular surgery, served on the DSMB for the INCREASE study and received consulting, lecture and advisory board fees from Guard Therapeutics, Marizyme, Abbott, and Abiomed, Data Monitoring Committee payments from Amopharma and patient fees from Guard Therapeutics. JoB received travel costs payments from Guard Therapeutics for an investigator meeting. DE is president of the ERAS Cardiac Society and was a member of Data Safety Monitoring Boards/Advisory Boards for Arthrex, Edwards Lifescience, Medella, Atricure, Pharmacosmos, Renibus, Alexion, and Genentech. AM, BdV, JaB, KM, ML, MT and NN declare no competing interests., (© 2024 The Author(s).)

Objective: Ischemic mitral regurgitation (MR) is generally associated with very poor outcomes and disappointing results, despite a seemingly perfect initial repair and optimal revascularization. We previously published our intermediate-term results of posterior leaflet augmentation without follow-up extending beyond 4 years. Our objective is to assess long-term durability of the repair, survival, and the causes of late mortality., Methods: Ninety-one patients with severe (4+) Carpentier Type IIIb ischemic MR underwent repair in a single center between 2003 and 2022 by method of posterior leaflet extension using a patch of bovine pericardium and a true-sized remodeling annuloplasty ring, with or without surgical revascularization. Serial echocardiography was performed over the years to ascertain valve competence and degree of ventricular remodeling, in addition to telephone follow-up and chart reviews., Results: The average age of patients was 67 ± 9.6 years. Mean follow-up was 8 ± 5 years with some extending to almost 20 years. One-, 5-, and 10-year freedom from recurrent significant MR, characterized as moderate or severe MR, was 98.6%, 85.5%, and 71.3%, respectively. Thirty-day mortality was 6.5%. One-, 5-, and 10-year survival was 85.5%, 64.4%, and 43.3%, respectively. Of all the mortalities, only 17.5% were proven to be directly cardiac related., Conclusions: The suggested repair technique offers satisfactory long-term outcomes with minimal residual regurgitation in surviving patients when used in context of ischemic MR. Despite durable repair, we have discovered that poor long-term survival is not directly related to cardiovascular causes., Competing Interests: Dr de Varennes is a consultant for Edwards Lifesciences Inc, Canada. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Objective: Intraoperative predictors of functional mitral valve (MV) stenosis after surgical repair of mitral regurgitation (MR) caused by prolapse remain poorly characterised. This study evaluated the effect of annuloplasty size on postoperative MV haemodynamics during exercise and evaluated predictors of MV hemodynamics., Methods: 104 patients were randomly assigned to leaflet resection or preservation for surgical repair of MR in the Canadian Mitral Research Alliance CardioLink-2 study. In this post hoc analysis, we compared MV haemodynamics between the two surgical groups and examined the relationship between annuloplasty size and MV haemodynamics 1 year after repair in the combined groups. Echocardiograms were performed at baseline and intraoperatively. Exercise transthoracic echocardiography was performed 1 year postoperatively. Multivariable linear regression analysis was used to identify predictors of exercise MV gradients at follow-up., Results: Mean age of participants was 65±10 years, and 83% were male. Median annuloplasty size was 34 (IQR 32-36). Dividing by the median, 48 (46%) had annuloplasty size of <34 mm and 56 (54%) had ≥34 mm. Mean and peak exercise gradients at 1 year were 11±5 mm Hg and 22±9 mm Hg in <34, and 6±3 mm Hg and 14±5 mm Hg in ≥34 (p<0.001). Rate of residual MR was similar in both groups. In multivariable analyses, annuloplasty size of ≥34 mm was associated with lower mean and peak exercise gradients at 12 months, after adjustment for repair type, age, sex, heart rate and body surface area (β -4.1, 95% CI -6 to -3, p<0.001, and β -7 95% CI -10 to -4, p<0.001, respectively). Intraoperative mean and peak MV gradients by transesophageal echocardiography independently predicted mean and peak resting and exercise gradients at follow-up (p<0.001). Similar results were obtained in both leaflet resection and preservation., Conclusion: Annuloplasty size of ≥34 mm is associated with a 4 and 7 mm Hg reduction in mean and peak exercise MV gradients, respectively, 1 year post MV repair regardless of the repair strategy used. Intraoperative TEE MV gradients predict exercise MV gradients 1 year post repair., Trial Registration Number: NCT02552771., Competing Interests: Competing interests: SV holds a tier 1 Canada Research chair in Cardiovascular Surgery; and reports receiving research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, EOCI Pharmacomm, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Otsuka, Pfizer, PhaseBio, Sanofi, Sun Pharmaceuticals and the Toronto Knowledge Translation Working Group. He is the president of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organisation. CDM is supported by a merit award from the University of Toronto Department of Anesthesiology and Pain Medicine and reports advisory board honoraria/consulting fees from Amgen, AstraZeneca, BioAge, Boehringer Ingelheim and PhaseBio and DSMB stipends from Beth Israel Deaconess Medical Center, Cerus and Takeda. BDV reports acting as a consultant for Edwards LifeSciences. MC is supported by the Ray and Margaret Elliot Chair in Surgical Innovation and reports speakers’ honoraria from Medtronic, Edwards Lifesciences, Terumo Aortic, Abbott Vascular and Cryolife. HL-P holds the Brazilian Ball Chair in Cardiology and reports receiving honoraria for speaking engagements from Lantheus Medical Imaging and Janssen. KC is listed as an inventor on a patent application by Boehringer Ingelheim on the use of dipeptidyl peptidase-4 inhibitors in heart failure and reports receiving research grants to his institution from AstraZeneca, Servier and Boehringer Ingelheim; support for travel to scientific meetings from Boehringer Ingelheim; and honoraria for speaking engagements and ad hoc participation in advisory boards from Servier, Merck, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Ferring, Novo Nordisk, Novartis and Janssen., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms. RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies., Methods and Analysis: This is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion. In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65 mg/kg.The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo. A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial. The study is a global multicentre study at approximately 30 sites., Ethics and Dissemination: The trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Münster (code '2021-778 f-A') and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites. The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal., Trial Registration Number: NCT05126303., Competing Interests: Competing interests: AZ received advisory board consultancy and travel reimbursements from Guard Therapeutics. TEL is employed by Guard Therapeutics., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: High-risk cardiac surgery is commonly complicated by low cardiac output syndrome (LCOS), which is associated with high mortality. There are limited data derived from multi-centre studies with adjudicated endpoints describing factors associated with LCOS and its downstream clinical outcomes., Methods and Results: The Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial evaluated prophylactic levosimendan vs. placebo in patients with a reduced ejection fraction undergoing coronary artery bypass grafting (CABG) and/or valve surgery. We conducted a pre-specified analysis on LCOS, which was characterized by a four-part definition. We constructed a multivariable logistical regression model to evaluate risk factors associated with LCOS and performed Cox proportional hazards modelling to determine the association of LCOS with 90-day mortality. A total of 186 (22%) of 849 patients in the LEVO-CTS trial developed LCOS. The factors most associated with a higher adjusted risk of LCOS were pre-operative ejection fraction [odds ratio (OR) 1.26; 95% confidence interval (CI): 1.08-1.46 per 5% decrease] and age (OR 1.13; 95% CI: 1.04-1.24 per 5-year increase), whereas isolated CABG surgery (OR 0.44, 95% CI: 0.31-0.64) and levosimendan use (OR 0.65; 95% CI: 0.46-0.92) were associated with a lower risk of LCOS. Patients with LCOS had worse outcomes, including renal replacement therapy at 30-day (10 vs. 1%) and 90-day mortality (16 vs. 3%, adjusted hazard ratio of 5.04, 95% CI: 2.66-9.55)., Conclusion: Low cardiac output syndrome is associated with a high risk of post-operative mortality in high-risk cardiac surgery., Competing Interests: Conflict of interest : A.K., Y.Z., S.v.D., A.I.D., R.W., M.A., and B.d.V. have none to declare; a part of R.H.M.’s salary was supported through DCRI that received funding for this trial from Tenax Therapeutics; C.D.M. was supported in part by a Merit Award from the University of Toronto Department of Anesthesia; R.D.L. received consulting fees from Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi and institutional grants from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; a part of J.H.A.’s salary was supported through Duke that received funding for this trial from Tenax Therapeutics. Other conflicts of interest are available at http://www.dcri.duke.edu/research/coi; S.G.G. received research grant support and consulting honoraria from Tenax Therapeutics; S.F. was supported in part by the Bernard S. Goldman Chair in Cardiovascular Surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: This study sought to compare characteristics and outcomes of patients who underwent surgical aortic valve replacement (SAVR) after being referred to a heart team (HT), to those of patients referred directly for SAVR., Methods: An analysis of patients who underwent SAVR from 2015 to 2020 was conducted. Patients were categorized into 3 groups, as follows: (i) H-HT: patients referred to the HT from 2015 to 2017 (historical cohort); (ii) C-HT: patients referred to the HT from 2018 to 2020 (contemporary cohort); and (iii) No-HT: patients referred directly to cardiac surgery from 2018 to 2020. Two subanalyses were performed: H-HT vs C-HT patients, and C-HT vs No-HT patients. The primary outcome was a composite of in-hospital mortality, prolonged intubation, reoperation, sternal wound infection, and stroke., Results: This study consisted of 288 patients, distributed as follows: H-HT (n = 45); C-HT (n = 51); and No-HT (n = 192). The mean ages of H-HT, C-HT, and No-HT patients was 76.3 ± 6.9 years, 73.3 ± 7.6 years, and 69.6 ± 9.7 years, respectively ( P  = 0.0001). H-HT, C-HT, and No-HT patients had average Society of Thoracic Surgeons scores of 4.8 ± 2.2, 3.2 ± 1.6, and 4.2 ± 2 ( P  = 0.002), respectively. The composite outcome rate was more than 5 times higher among H-HT patients compared to that among the C-HT patients (20.0 vs 3.9%, P  = 0.02), and was numerically higher in No-HT compared to C-HT patients (13.0 vs 3.9%, P  = 0.07)., Conclusions: Referral to an HT appears to be primarily driven by higher chronological age rather than overall risk profile. Patients assessed by the HT prior to undergoing SAVR have a low incidence of complications, comparable to that among patients referred directly to cardiac surgery., (© 2022 The Authors.)

Background The Essential Frailty Toolset (EFT) was shown to be easy to use and predictive of adverse events in patients undergoing aortic valve replacement procedures. The objective of this study was to evaluate the EFT in patients undergoing coronary artery bypass grafting procedures. Methods and Results The McGill Frailty Registry prospectively included patients ≥60 years of age undergoing urgent or elective isolated coronary artery bypass grafting between 2011 and 2018 at 2 hospitals. The preoperative EFT was scored 0 to 5 points as a function of timed chair rises, Mini-Mental Status Examination, serum albumin, and hemoglobin. The primary outcome was all-cause mortality assessed by Cox proportional hazards regression. The cohort consisted of 500 patients with a mean age of 71.4 ± 6.4 years, of which 27% presented with acute coronary syndromes requiring urgent surgery. The mean EFT was 1.3 ± 1.1 points, 132 (26%) were nonfrail, 298 (60%) were prefrail, and 70 (14%) were frail. Over a median follow-up of 4.0 years, 78 deaths were observed. In nonfrail, prefrail, and frail patients, survival at 1 year was 98%, 95%, and 91%, and at 5 years was 89%, 83%, and 63% ( P <0.001). After adjustment, each incremental EFT point was associated with a hazard ratio of 1.28 (95% CI, 1.05-1.56) and frail patients had a 3-fold increase in all-cause mortality. Conclusions The EFT is a pragmatic and highly prognostic tool to assess frailty and guide decisions for coronary artery bypass grafting in older adults. Furthermore, the EFT may be actionable through targeted interventions such as cardiac rehabilitation and nutritional optimization.

Background: Few studies have measured frailty as a potential reason for foregoing transcatheter aortic valve replacement (TAVR) in older adults with severe aortic stenosis (AS). This study sought to determine the impact of frailty and other clinician-cited reasons on restricted mean survival time (RMST)., Methods: An analysis of the McGill Frailty Registry was conducted between 2014 and 2018 at the McGill University Health Center Structural Valve Clinic. Consecutive nonsurgical patients referred for TAVR were included. In those that underwent balloon aortic valvuloplasty or medical management, the primary clinician-cited reason for foregoing TAVR was codified. Vital status was ascertained at 1 year and analysed using RMST and Kaplan-Meier analyses., Results: The study consisted of 373 patients with a mean age of 82.4 years, of which 233 underwent TAVR and 140 did not. Patients who did not undergo TAVR were more likely to be nonagenarians, with left ventricular dysfunction, chronic kidney disease, dementia, disability, depression, malnutrition, and frailty. The primary clinician-cited reason was: comorbidity in 34%, frailty in 23%, procedural feasibility and risks in 16%, and mild or unrelated symptoms in 27%. Compared to the TAVR group, 1-year RMST was reduced by 2.0 months in the medical management group (95% CI 1.2, 2.7) and by 1.1 months in the valvuloplasty group (95% CI -0.2, 2.5)., Conclusions: Patients with severe AS referred for TAVR may never undergo the procedure on the basis of comorbidity, frailty, procedural issues, and symptoms. The best treatment decision is one that follows from multi-disciplinary assessment encompassing frailty.

Introduction: Few bioprosthetic valved conduits for aortic root surgery are commercially available. Long-term Warfarin therapy (mechanical), potential root calcification (xeno- or homograft valves), and the need for additional ascending aorta grafts are concerns associated with currently used valved conduits. A simplified, self-assembled bioroot conduit comprising currently available materials that facilitates future intervention and exhibits advantages of a bioprosthesis was used., Methods: From November 2015 to January 2017, 17 consecutive patients underwent urgent or elective aortic root surgery. A bioroot conduit, constructed using 28 or 30 mm of sinus of Valsalva Gelweave tube graft and a 3 to 5 mm smaller bioprosthetic Trifecta valve sewn into the sinus of Valsalva base, was preconstructed in the operating room before sternotomy. The size of the valved conduit was based on the distal ascending aorta or proximal arch and not aortic annular dimension. The bioroot was sutured to the native aortic annulus at the level of the bottom skirt of the Valsalva graft without contacting the sewing cuff of the bioprosthetic valve., Results: All patients survived the operation and were discharged home without long-term anticoagulation therapy. The mean age was 65 ± 12 years, and 13 patients were male. The cardiopulmonary bypass duration was 169 ± 84 minutes, and the cross-clamp (XC) duration was 110 ± 32 minutes. The operation was elective in 12 patients, urgent/emergent in five, and redo in three., Conclusion: A simplified self-assembled bioroot Bentall conduit is appropriate for aortic root reconstruction. Use of a patient-tailored valved conduit will not prolong the cardiac ischemic time and will facilitate future valve replacement., (© 2019 Wiley Periodicals, Inc.)

AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%-79%; P =0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage ( P =0.53) or the total duration of AKI ( P =0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%-20%; P =0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients., (Copyright © 2018 by the American Society of Nephrology.)

Aims: Transcatheter aortic valve implantation for a failing surgical bioprosthesis (TAV-in-SAV) has become an alternative for patients at high risk for redo surgical aortic valve replacement (redo-SAVR). Comparisons between these approaches are non-existent. This study aimed to compare clinical and echocardiographic outcomes of patients undergoing TAV-in-SAV versus redo-SAVR after accounting for baseline differences by propensity score matching., Methods and Results: Patients from seven centres in Europe and Canada who had undergone either TAV-in-SAV (n=79) or redo-SAVR (n=126) were identified. Significant independent predictors used for propensity scoring were age, NYHA functional class, number of prior cardiac surgeries, urgent procedure, pulmonary hypertension, and COPD grade. Using a calliper range of ±0.05, a total of 78 well-matched patient pairs were found. All-cause mortality was similar between groups at 30 days (6.4% redo-SAVR vs. 3.9% TAV-in-SAV; p=0.49) and one year (13.1% redo-SAVR vs. 12.3% TAV-in-SAV; p=0.80). Both groups also showed similar incidences of stroke (0% redo-SAVR vs. 1.3% TAV-in-SAV; p=1.0) and new pacemaker implantation (10.3% redo-SAVR vs. 10.3% TAV-in-SAV; p=1.0). The incidence of acute kidney injury requiring dialysis was numerically lower in the TAV-in-SAV group (11.5% redo-SAVR vs. 3.8% TAV-in-SAV; p=0.13). The TAV-in-SAV group had a significantly shorter median total hospital stay (12 days redo-SAVR vs. 9 days TAV-in-SAV; p=0.001)., Conclusions: Patients with aortic bioprosthesis failure treated with either redo-SAVR or TAV-in-SAV have similar 30-day and one-year clinical outcomes.

Lipoprotein(a), or Lp(a), significantly increased alkaline phosphatase activity, release of phosphate, calcium deposition, hydroxyapatite, cell apoptosis, matrix vesicle formation, and phosphorylation of signal transduction proteins; increased expression of chondro-osteogenic mediators; and decreased SOX9 and matrix Gla protein (p < 0.001). Inhibition of MAPK38 and GSK3β significantly reduced Lp(a)-induced calcification of human aortic valve interstitial cells (p < 0.001). There was abundant presence of Lp(a) and E06 immunoreactivity in diseased human aortic valves. The present study demonstrates a causal effect for Lp(a) in aortic valve calcification and suggests that interfering with the Lp(a)pathway could provide a novel therapeutic approach in the management of this debilitating disease.

Objective: The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With accumulating evidence demonstrating that valve calcification recapitulates bone development, the crucial roles of noncanonical Wnt ligands WNT5a, WNT5b, and WNT11 in osteogenesis make them critical targets in the study of aortic valve calcification., Approach and Results: Using immunohistochemistry, real-time qPCR, Western blotting, and tissue culture, we examined the tissue distribution of WNT5a, WNT5b, and WNT11 in noncalcified and calcified aortic valves and their effects on human aortic valve interstitial cells (HAVICs). Only focal strong immunostaining for WNT5a was seen in and around areas of calcification. Abundant immunostaining for WNT5b and WNT11 was seen in inflammatory cells, fibrosis, and activated myofibroblasts in areas of calcified foci. There was significant correlation between WNT5b and WNT11 overall staining and presence of calcification, lipid score, fibrosis, and microvessels ( P <0.05). Real-time qPCR and Western blotting revealed abundant expression of both Wnts in stenotic aortic valves, particularly in bicuspid valves. Incubation of HAVICs from noncalcified valves with the 3 noncanonical Wnts significantly increased cell apoptosis and calcification ( P <0.05). Treatment of HAVICs with the mitogen-activated protein kinase-38β and GSK3β inhibitors significantly reduced their mineralization ( P <0.01). Raman spectroscopy identified the inorganic phosphate deposits as hydroxyapatite and showed a significant increase in hydroxyapatite deposition in HAVICs in response to WNT5a and WNT11 ( P <0.05). Similar crystallinity was seen in the deposits found in HAVICs treated with Wnts and in calcified human aortic valves., Conclusions: These findings suggest a potential role for noncanonical Wnt signaling in the pathogenesis of aortic valve calcification., (© 2016 American Heart Association, Inc.)

Background: Prolonged controlled mechanical ventilation (CMV) in humans and experimental animals results in diaphragm fibre atrophy and injury. In animals, prolonged CMV also triggers significant declines in diaphragm myofibril contractility. In humans, the impact of prolonged CMV on myofibril contractility remains unknown. The objective of this study was to evaluate the effects of prolonged CMV on active and passive human diaphragm myofibrillar force generation and myofilament protein levels., Methods and Results: Diaphragm biopsies were obtained from 13 subjects undergoing cardiac surgery (control group) and 12 brain-dead organ donors (CMV group). Subjects in each group had been mechanically ventilated for 2-4 and 12-74 h, respectively. Specific force generation of diaphragm myofibrils was measured with atomic force cantilevers. Rates of force development (Kact), force redevelopment after a shortening protocol (Ktr) and relaxation (Krel) in fully activated myofibrils (pCa(2+)=4.5) were calculated to assess myosin cross-bridge kinetics. Myofilament protein levels were measured with immunoblotting and specific antibodies. Prolonged CMV significantly decreased active and passive diaphragm myofibrillar force generation, Kact, Ktr and Krel. Myosin heavy chain (slow), troponin-C, troponin-I, troponin-T, tropomyosin and titin protein levels significantly decreased in response to prolonged CMV, but no effects on α-actin, α-actinin or nebulin levels were observed., Conclusions: Prolonged CMV in humans triggers significant decreases in active and passive diaphragm myofibrillar force generation. This response is mediated, in part, by impaired myosin cross-bridge kinetics and decreased myofibrillar protein levels., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Surgical sutureless aortic valves have the potential for shorter procedural times and could benefit patients with increased risk. The Enable (Medtronic Inc, Minneapolis, Minn) valve is a bioprosthesis housed in a Nitinol cage allowing folding and deployment once implanted. We aimed to evaluate the early clinical and echocardiographic results with the Enable valve., Methods: Patients with aortic stenosis, Society of Thoracic Surgeons score greater than 5.0%, the need for combined procedures, and frailty were considered for Enable implantation., Results: Between August 2012 and October 2014, 63 patients underwent implantation of the Enable valve (Medtronic Inc, Minneapolis, Minn). Thirty patients underwent isolated aortic valve replacement. Combined procedures were aortic valve replacement/coronary artery bypass grafting (26), aortic valve replacement/mitral valve repair (2), aortic valve replacement/mitral valve repair/coronary artery bypass grafting (2), and aortic valve replacement/ascending aortic graft (3). Predicted Society of Thoracic Surgeons score was 8.06 ± 7.73 (0.94-41.30). Implant success was 100%. Mean crossclamp time for isolated aortic valve replacement was 44 ± 14 minutes (30-91). Thirty-day mortality was 1.6% (1/63), and late mortality was 3.2% (2/62). No mortality was valve related. Intraoperative need for revision was 6.3% (4/63). Early migration requiring reoperation occurred in 1.6% of patients (1/63). Postoperative indexed aortic valve area was 1.08 ± 0.22 cm(2)/m(2), and peak and mean gradients were 17 ± 7 mm Hg and 9 ± 4 mm Hg, respectively. The rate of complications was as follows: pacemaker 3.1% (2/63), transient ischemic attack 1.6% (1/63), other thromboembolic events 0%, bleeding 0%, and endocarditis 0%. Mean follow-up was 10 ± 8 months. At latest follow-up, 61 patients were in New York Heart Association class I. Moderate or severe aortic regurgitation did not develop in any patients in the follow-up period., Conclusions: The Enable bioprosthesis is an acceptable alternative to conventional aortic valve replacement in higher-risk patients. The early hemodynamic performance seems favorable., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Higher morbidity and mortality rates are seen amongst patients presenting with hyperlactatemia in the postoperative period. The purpose of this study was to determine the relationship between persistent elevations in lactate and poor ICU outcome in post-cardiac surgery patients., Methods: This was a retrospective matched cohort analysis of cardiac surgery patients undergoing bypass and/or valve surgery in a university hospital centre. Selection criteria were: cardiac bypass and/or valve surgery; admission to the ICU for > 24 h postoperatively; and peak lactate ≥ 3.0 mmol/L. Hyperlactatemic patients were matched to 2 normolactatemic patients. Multivariable conditional logistic regression was used to determine predictors of hyperlactatemia and mortality., Results: Four hundred sixty-nine post-cardiac surgery patients were admitted to the ICU for > 24 h. 144 of these patients had an arterial blood lactate ≥ 3.0 mmol/L. Amongst the mortalities, 78.9 % presented with hyperlactatemia. Independent risk factors predictive of a lactate ≥ 3.0 mmol/L were preoperative IABP insertion (RR 2.8, CI 1.1-7.2) and postoperative acute kidney injury (RR 3.2, CI 2.1-5.4). Patients whose lactate concentrations continued to increase >30 h postoperatively were more likely to die (RR 8.44 CI 2.50-28.53)., Conclusions: The persistence of hyperlactatemia is a more important determinant of postoperative outcome than the absolute value of the peak lactate concentration. A simple postoperative lactate washout does not sufficiently explain this lactate accumulation. Mortality is proposed to be secondary to a state of ongoing hypoperfusion.

Aims: A comprehensive description of transcatheter heart valve (THV) failure has not been performed. We undertook a systematic review to investigate the aetiology, diagnosis, management, and outcomes of THV failure., Methods and Results: The systematic review was performed in accordance with the PRISMA guidelines using EMBASE, MEDLINE, and Scopus. Between December 2002 and March 2014, 70 publications reported 87 individual cases of transcatheter aortic valve implantation (TAVI) failure. Similar to surgical bioprosthetic heart valve failure, we observed cases of prosthetic valve endocarditis (PVE) (n = 34), structural valve failure (n = 13), and THV thrombosis (n = 15). The microbiological profile of THV PVE was similar to surgical PVE, though one-quarter had satellite mitral valve endocarditis, and surgical intervention was required in 40% (75% survival). Structural valve failure occurred most frequently due to leaflet calcification and was predominantly treated by redo-THV (60%). Transcatheter heart valve thrombosis occurred at a mean 9 ± 7 months post-implantation and was successfully treated by prolonged anticoagulation in three-quarters of cases. Two novel causes of THV failure were identified: late THV embolization (n = 18); and THV compression (n = 7) following cardiopulmonary resuscitation (CPR). These failure modes have not been reported in the surgical literature. Potential risk factors for late THV embolization include low prosthesis implantation, THV undersizing/underexpansion, bicuspid, and non-calcified anatomy. Transcatheter heart valve embolization mandated surgery in 80% of patients. Transcatheter heart valve compression was noted at post-mortem in most cases., Conclusion: Transcatheter heart valves are susceptible to failure modes typical to those of surgical bioprostheses and unique to their specific design. Transcatheter heart valve compression and late embolization represent complications previously unreported in the surgical literature., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)