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Liquid biopsy has dramatically changed cancer management in the last decade; however, despite the huge number of miRNA signatures available for diagnostic or prognostic purposes, it is still unclear if dysregulated miRNAs in the bloodstream could be used to develop miRNA-based therapeutic approaches. In one author’s previous work, nine miRNAs were found to be dysregulated in early-stage colon cancer (CRC) patients by NGS analysis followed by RT-dd-PCR validation. In the present study, the biological effects of the targeting of the most relevant dysregulated miRNAs with anti-miRNA peptide nucleic acids (PNAs) were verified, and their anticancer activity in terms of apoptosis induction was evaluated. Our data demonstrate that targeting bloodstream up-regulated miRNAs using anti-miRNA PNAs leads to the down-regulation of target miRNAs associated with inhibition of the activation of the pro-apoptotic pathway in CRC cellular models. Moreover, very high percentages of apoptotic cells were found when the anti-miRNA PNAs were associated with other pro-apoptotic agents, such as sulforaphane (SFN). The presented data sustain the idea that the targeting of miRNAs up-regulated in the bloodstream with a known role in tumor pathology might be a tool for the design of protocols for anti-tumor therapy based on miRNA-targeting molecules.

Objective: We aim to show the step-by-step surgical technique of mitral valve re-repair by means of a repeated right anterior minithoracotomy in a case of a procedure-related early mitral valve repair failure due to left ventricular positive remodeling and chordal pseudo-elongation. Methods: The patient was readdressed to our institution for an early severe mitral valve regurgitation, less than a year after performing a right minithoracotomy mitral valve repair (42-mm annular ring implantation, P2 triangular resection, and P2 neochord positioning). The mechanism was attributed to a positive left ventricle remodeling and neochordal pseudo-elongation. Therefore, we decided to perform a mitral valve re-repair in a redo minimally invasive cardiac surgery. We describe in a video-guided step-by-step fashion the surgical procedure, from the reopening of the right anterior minithoracotomy to the surgical strategy chosen to address the re-repair, guided by the mechanism of the previous repair failure. Results: We replaced the previously implanted ring with a smaller one and positioned a new polytetrafluoroethylene 4-0 neochord at the P2 level. The patient was discharged home on the fifth postoperative day after an uneventful hospital stay. Predischarge echocardiogram demonstrated undetectable residual mitral valve regurgitation. At 3-month follow-up, echocardiographic and clinical data were encouraging. At 9-month follow-up, the patient endorsed no recurrence of cardiologic symptoms. Conclusions: Redo minimally invasive cardiac surgery is a viable option even in case of a mitral valve re-repair due to previous repair failure, especially when procedure related in degenerative mitral disease. Combining the benefits of mitral valve re-repair with those of a minimally invasive surgery may optimize short-term and long-term outcomes.

BACKGROUND AND AIM OF THE STUDY The aim of this meta-analysis was to compare short- and long-term outcomes of patients undergoing mitral annuloplasty (MA) with or without papillary muscle surgery (PMS) for the treatment of ischemic mitral regurgitation (IMR). METHODS A systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were performed. RESULTS Nine studies met the inclusion criteria. This meta-analysis identified 478 patients: 228 patients underwent MA alone and 250 patients underwent concomitant PMS. Early mortality was similar between two groups (odds ratio [OR] 1.14, 95% confidence interval [CI], 0.51-2.53; P = .75). PMS was associated at follow-up with a higher freedom from cardiac-related events (P = .050); moreover, although both surgical techniques had a positive impact on ventricular remodeling, the PMS group showed a significant higher reduction of left ventricle end-diastolic diameter (OR, 4.89, 95% CI, 2.77-7.01; P

After a median full sternotomy, cardiopulmonary bypass is installed in the usual manner. Apical ventriculotomy is performed through the infarcted myocardium. Polypropylene pledgeted mattress sutures are passed from the right to the left ventricular side through the ventricular septal defect, with the pledgets remaining on the right ventricle. Great care must be taken to place the suture on healthy myocardium and away from the edge of the ventricular septal defect; otherwise the chances of a recurrent postoperative ventricular septal defect would increase. The sutures are subsequently positioned through a heterologous patch, previously prepared to be appropriate for the ventricular septal defect closure. A collar of 3 to 4 cm is left on the external side of the patch. A 4-0 polypropylene running suture is placed through this collar and the left ventricle to further reinforce the ventricular septal defect closure. The left ventricular incision is closed with polypropylene 3-0 continuous sutures. For each ventricular edge, the running suture is passed through 2 polytetrafluoroethylene felts: one on the endoventricular side and the other on the epicardial side. Finally, the suture line is reinforced with a continuous 2-0 polypropylene suture, which is passed through the polytetrafluoroethylene felts, the ventricular wall, and the heterologous patch used to close the ventricular septal defect.

A significant proportion of patients undergoing aortic valve replacement have a dilated ascending aorta; presence of an ascending aorta aneurysm is viewed as a contraindication for sutureless valve implantation for the potential risk of prosthesis dislodgment. We describe our technique of sutureless prosthesis implantation and concomitant ascending aorta replacement through an upper ministernotomy. Seven patients underwent aortic valve replacement with a sutureless prosthesis and concomitant ascending aorta replacement between November 2014 and October 2016. A J-shaped upper ministernotomy was performed in all patients. Diameter of vascular graft for the replacement of the dilated ascending aorta was chosen according to the size of the selected prosthesis, to recreate a ratio between diameters of the new sinotubular junction and the aortic annulus that should be less than 1.3. Postoperatively. no patient died in hospital. No paravalvular leakage or prosthesis dislodgment was reported. Mean ± SD cardiopulmonary bypass and cross-clamp times were 142 ± 52 minutes and 85 ± 18 minutes, respectively. In patients undergoing aortic valve replacement and ascending aorta replacement, sutureless valve implantation is a safe and reproducible procedure associated with good postoperative results.

Massimiliano Povero,1 Antonio Miceli,2,3 Lorenzo Pradelli,1 Matteo Ferrarini,2 Matteo Pinciroli,4 Mattia Glauber2 1AdRes Health Economics and Outcomes Research, Turin, Italy; 2Minimally Invasive Cardiothoracic Department, Istituto Clinico Sant’Ambrogio, Gruppo Ospedaliero San Donato, Milan, Italy; 3Bristol Heart Institute, University of Bristol, Bristol, UK; 4LivaNova, Milan, Italy Background: Meta-analyses of studies comparing transcatheter aortic valve implants (TAVIs) and sutureless aortic valve replacement (SU-AVR) show differing effectiveness and safety profiles. The approaches also differ in their surgical cost (including operating room and device).Objective: The objective of this study was to assess the incremental cost-utility of SU-AVR vs TAVIs for the treatment of intermediate- to high-risk patients in the US, Germany, France, Italy, UK, and Australia.Methods: A patient-level simulation compares in-hospital pathways of patients undergoing SU-AVR or TAVIs; later, patient history is modeled at the cohort level. Hospital outcomes for TAVIs reproduce data from recent series; in SU-AVR patients, outcomes are obtained by applying relative efficacy estimates in a recent meta-analysis on 1,462 patients. After discharge, survival depends on the development of paravalvular leak and the need for dialysis. A comprehensive third-party payer perspective encompassing both in-hospital and long-term costs was adopted.Results: Due to lower in-hospital (4.1% vs 7.0%) and overall mortality, patients treated with SU-AVR are expected to live an average of 1.25 years more compared with those undergoing TAVIs, with a mean gain of 1.14 quality-adjusted life-years. Both in-hospital and long-term costs were lower for SU-AVR than for TAVIs with total savings ranging from $4,158 (France) to $20,930 (US).Conclusion: SU-AVR results dominant when compared to TAVIs in intermediate- to high-risk patients. Both in-hospital and long-term costs are lower for SU-AVR than for TAVI patients, with concomitant significant gains in life expectancy, both raw and adjusted for the quality of life. Keywords: sutureless valve, aortic valve replacement, TAVI, DES model, cost-utility&nbsp

Objective To define the benefit of sutureless and rapid deployment valves in current minimally invasive approaches in isolated aortic valve replacement. Methods A panel of 28 international experts with expertise in both minimally invasive aortic valve replacement and rapid deployment valves was constituted. After thorough literature review, the experts rated evidence-based recommendations in a modified Delphi approach. Results No guideline could be retrieved. Thirty-three clinical trials and 9 systematic reviews could be identified for detailed text analysis to obtain a total of 24 recommendations. After rating by the experts 12, final recommendations were identified: preoperative computed to-mographic scan as well as intraoperative transesophageal echocardiography are highly recommended. Suitable annular sizes are 19 to 27 mm. There is a contraindication for bicuspid valves only for type 0 and for annular abscess or destruction due to infective endocarditis. The use of sutureless and rapid deployment valves reduces extracorporeal circulation and aortic cross-clamp time and leads to less early complications as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions, paravalvular leakages and aortic regurgitation, and renal replacement therapy, respectively. These clinical outcomes result in reduced intensive care unit and hospital stay and reduced costs. The use of sutureless and rapid deployment valves will lead to a higher adoption rate of minimally invasive approaches in aortic valve replacement. Respect should be taken to a necessary short learning curve for both sutureless and minimally invasive programs. Conclusions Sutureless and rapid deployment aortic valve replacement together with minimally invasive approaches offers an attractive option in aortic valve placement for patients requiring biological valve replacement.

Background:Erdheim-Chester disease (ECD) is a chronic inflammatory disease characterized by infiltration of bone and other tissues by foamy macrophages. These cells exhibit activating mutations along the MAPK pathway, most commonly BRAFV600E, and increased production of pro-inflammatory cytokines. Although this dual neoplastic-inflammatory nature of ECD has long fascinated scientists, the mechanistic link between these two features remains elusive. We hypothesized that Trained Immunity (TI), a pro-inflammatory cell program physiologically elicited in monocytes/macrophages upon activation of the MAPK pathway, might represent the missing link between oncogenic transformation and pro-inflammatory activation in ECD.Objectives:In this study, we aimed at determining the role of TI in the pathogenesis of ECD, and to evaluate the therapeutic potential of targeting this mechanism for the treatment of inflammation.Methods:We developed innovative models to study ECD pathogenesisin vitro(based on lentiviral transduction and ectopic expression of BRAFV600E in primary human monocytes), as well asex vivo(3D culture of ECD tissue biopsies in bioreactor). Functional and mechanistic features of TI, including typical changes in cell energy metabolism and epigenetics, were investigated by assessing I) cytokine and lactate production; II) mitochondrial respiration with Seahorse flux analyzer; III) glucose, glutamine and cholesterol metabolism with unbiased and targeted metabolomics analyses; IV) epigenetic changes with ChIP PCR; V) transcriptome changes with RNA sequencing.Results:Activation of the MAPK pathway induced by BRAFV600E in macrophages induces changes in the epigenetic and gene expression landscape, cell energy metabolism, and cytokine production characteristic of TI. In particular, changes in cell energy metabolism of macrophages are characterized by increased glycolysis, glutamine metabolism, and cholesterol synthesis. This metabolic rewiring is needed to sustain rampant, constitutive production of pro-inflammatory cytokines.Conclusion:A role emerges for TI in the pathogenesis and pro-inflammatory activation of ECD. However, maladaptive activation of this mechanism is likely common to the pathogenesis of other inflammatory and rheumatologic diseases. Since drugs targeting TI programs are already entering the clinical arena, the identification of this mechanism in the pathogenesis of inflammatory and rheumatologic conditions may promptly translate into novel, effective treatment options for affected patients.Disclosure of Interests:Riccardo Biavasco Employee of: Bluebird, Raffaella Molteni: None declared, Davide Stefanoni: None declared, Marina Ferrarini: None declared, Elisabetta Ferrero: None declared, Simone Cenci: None declared, Simone Cardaci: None declared, Alessandra Boletta: None declared, Laura Cassina: None declared, Gianfranco Di Stefano: None declared, Jorge Dominguez Andres: None declared, Claudio Doglioni: None declared, Travis Nemkov: None declared, Ivan Merelli: None declared, Angelo D’Alessandro: None declared, Eugenio Montini: None declared, Mihai Netea: None declared, Lorenzo Dagna: None declared, Giulio Cavalli Consultant of: SOBI, Pfizer, Sanofi, Novartis, Paid instructor for: SOBI, Novartis, Speakers bureau: SOBI, Novartis

The use of artificial polytetrafluoroethylene (PTFE) chordae has been widely adopted in the setting of mitral valve repair. In this tutorial, we present a modified technique for neochordae placement using a semi-rigid complete ring, with a chordal sizing system. This ring was introduced with the aim of standardizing neo-chordae implantation and we introduce a modification of the implantation technique in the presence of myxomatous leaflets.

Background Aortic stenosis is the most common valvular disease and has a dismal prognosis without surgical treatment. The aim of this meta‐analysis was to quantitatively assess the comparative effectiveness of the Perceval (LivaNova) valve versus conventional aortic bioprostheses. Methods and Results A total of 6 comparative studies were identified, including 639 and 760 patients who underwent, respectively, aortic valve replacement with the Perceval sutureless valve (P group) and with a conventional bioprosthesis (C group). Aortic cross‐clamping and cardiopulmonary bypass duration were significantly lower in the P group. No difference in postoperative mortality was shown for the P and C groups (2.8% versus 2.7%, respectively; odds ratio [OR]: 0.99 [95% confidence interval ( CI ), 0.52–1.88]; P =0.98). Incidence of postoperative renal failure was lower in the P group compared with the C group (2.7% versus 5.5%; OR: 0.45 [95% CI , 0.25–0.80]; P =0.007). Incidence of stroke (2.3% versus 1.7%; OR: 1.34 [95% CI , 0.56–3.21]; P =0.51) and paravalvular leak (3.1% versus 1.6%; OR : 2.52 [95% CI , 0.60–1.06]; P =0.21) was similar, whereas P group patients received fewer blood transfusions than C group patients (1.16±1.2 versus 2.13±2.2; mean difference: 0.99 [95% CI , −1.22 to −0.75]; P =0.001). The incidence of pacemaker implantation was higher in the P than the C group (7.9% versus 3.1%; OR : 2.45 [95% CI , 1.44–4.17]; P =0.001), whereas hemodynamic Perceval performance was better (transvalvular gradient 23.42±1.73 versus 22.8±1.86; mean difference: 0.90 [95% CI , 0.62–1.18]; P =0.001), even during follow‐up (10.98±5.7 versus 13.06±6.2; mean difference: −2.08 [95% CI , −3.96 to −0.21]; P =0.030). We found no difference in 1‐year mortality. Conclusions The Perceval bioprosthesis improves the postoperative course compared with conventional bioprostheses and is an option for high‐risk patients.

OBJECTIVES The aim of this study was to compare early outcomes and mid-term survival of high-risk patients undergoing minimally invasive aortic valve replacement through right anterior mini-thoracotomy (RT) with sutureless valves versus patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis. METHODS From October 2008 to March 2013, 269 patients with severe aortic stenosis underwent either RT with perceval S sutureless valves (n = 178 patients, 66.2%) or TAVI (n = 91, 33.8%: 44 transapical and 47 trans-femoral). Of these, 37 patients undergoing RT with the perceval S valve were matched to a TAVI group by the propensity score. RESULTS Baseline characteristics were similar in both groups (mean age 79 ± 6 years) and the median logistic EuroSCORE was 14% (range 9-20%). In the matched group, the in-hospital mortality rate was 8.1% (n = 3) in the TAVI group and 0% in the RT group (P = 0.25). The incidence rate of stroke was 5.4% (n = 2) versus 0% in the TAVI and RT groups (P = 0.3). In the TAVI group, 37.8% (n = 14) had mild paravalvular leakage (PVL) and 27% (n = 10) had moderate PVL, whereas 2.7% (n = 1) had mild PVL in the RT group (P < 0.001). One- and 2-year survival rates were 91.6 vs 78.6% and 91.6 vs 66.2% in patients undergoing RT with the perceval S sutureless valve compared with those undergoing TAVI, respectively (P = 0.1). CONCLUSIONS Minimally invasive aortic valve replacement with perceval S sutureless valves through an RT is associated with a trend of better early outcomes and mid-term survival compared with TAVI.

Surgical aortic valve replacement (AVR) is increasingly performed in elderly patients with good perioperative outcomes and long-term survival, resulting in significant health-related quality-of-life benefits. This study aimed to evaluate the outcome of patients aged ≥ 80 years undergoing isolated AVR through a right anterior minithoracotomy (RAMT) and compare it with a full sternotomy (FS).Two hundred and eighty-three elderly patients aged 80 years or more underwent isolated AVR between February 2001 and September 2013. With propensity score matching (1 : 1), the outcomes of patients having minimally invasive surgery (RAMT) were compared with those in whom the FS approach had been employed (100 vs 100 patients). TAVRs and partial sternotomy cases were excluded from the analysis.There were two conversions in the RAMT group. Operative times did not significantly differ in the two groups. Patients in the RAMT group received a larger-sized prosthesis (P0.001) and were more likely to receive sutureless valves (P0.001). Shorter time for extubation (P0.001) and shorter hospital length of stay (P = 0.005) were observed in the RAMT group. Zero vs 4 (4.0%) (P = 0.043) patients had postoperative stroke and 2 (2.0%) vs zero (P = 0.16) had a transient ischaemic attack in the RAMT versus FS group, respectively. We registered the same rate of permanent pacemaker implant (P = 0.47) and that of new-onset atrial fibrillation (P = 0.28) for both groups. Six patients died, with no significant difference for in-hospital mortality (P = 0.68). No variable had a statistically significant predictive value for in-hospital mortality. RAMT patients were more likely to be discharged home directly or via rehabilitation (P = 0.031). FS, along with four other factors, independently predicted longer hospital stay. Though the median follow-up duration was longer in the FS group (59 vs 24 months, P0.001), the two groups had similar survival rates at 5 years (80 vs 81%, P = 0.37). Ten factors were associated with long-term survival by Cox regression analysis, and RAMT had no statistical impact (P = 0.38).Minimally invasive AVR through right anterior minithoracotomy can be safely performed in patients aged ≥80 years with acceptable morbidity and mortality rates. It is an expeditious and effective alternative to full sternotomy AVR and might be associated with lower postoperative stroke incidence, earlier extubation and shorter hospital stay.

Objective Transaortic left ventricular septal myectomy described by Morrow is a classical procedure for the treatment of systolic anterior motion of the mitral apparatus associated with hypertrophic obstructive cardiomyopathy (HOCM). We aimed to review our results of transmitral septal myectomy and mitral valve repair/replacement in patients with intrinsic mitral valve disease associated with HOCM, operated on through a minimally invasive approach. Methods Between 2005 and 2014, 19 patients [7 men (37%); mean (SD) age, 69.4 (14.5) years] were treated with minimally invasive approach for degenerative mitral regurgitation and HOCM. Preoperative peak left ventricular outflow tract (LVOT) gradient was 66 (24) mm Hg. Severe mitral regurgitation was diagnosed in 16 cases (84%). New York Heart Association functional class III to IV heart failure was present in 13 patients (68%). Results Fifteen patients (79%) underwent mitral valve replacement, and four patients (21%) underwent mitral valve repair. Left ventricular outflow tract obstruction was corrected directly in all patients via the mitral valve with septal myectomy/myotomy, avoiding aortotomy in majority of the patients. No significant prolongation of extracorporeal circulation/aortic cross-clamping times was observed ( P = 0.41 and P = 0.67, respectively) when compared with a similar population without HOCM. No iatrogenic ventricular septal defect developed in treated patients. No hospital mortality occurred. Resting LVOT gradient reduced at discharge to 13 (22) mm Hg ( P = 0.025). Conclusions Transmitral left ventricular septal myectomy in patients with degenerative mitral valve disease is quite a simple, feasible, and effective technique and does not require aortotomy in most cases. It can be performed with low early mortality and satisfactory resolution of LVOT obstruction in a minimally invasive setting.

A semi-rigid complete ring including a chordal sizing system has been introduced with the aim of standardizing neochordae implantation. Instructions for use of this ring suggest to pass the neochordae through the free margin of mitral leaflets. We introduce a modification of this technique in the presence of myxomatous leaflets.

Objectives The aim of this meta-analysis was to compare outcomes of patients undergoing transcatheter aortic valve implantation (TAVI) with those undergoing surgical aortic valve replacement using sutureless valves. Methods A systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was performed. Results No randomized controlled trials were identified. Six comparative studies using propensity score matching met the inclusion criteria. This meta-analysis identified 1462 patients in that 731 patients underwent surgical aortic valve replacement using sutureless valves (SU) and 731 patients underwent a TAVI. The 30-day or in-hospital mortality was lower in the SU group [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.36-0.80; P = 0.003]. In the TAVI group, the incidence of postoperative stroke was higher (OR 0.36, 95% CI 0.17-0.79; P = 0.01). The incidence of moderate or severe paravalvular regurgitation was higher in the TAVI group (OR 0.22, 95% CI 0.14-0.35; P = 0.001). There were neither differences in the postoperative renal failure (OR 1.44, 95% CI 0.46-4.58; P = 0.53) nor in the number of patients requiring postoperative pacemaker implantation (OR 1.06, 95% CI 0.54-2.08; P = 0.86). Patients in the SU group required more transfusions (OR 4.47, 95% CI 2.77-7.21; P = 0.0001), whereas those in the TAVI group had higher major vascular complications (OR 0.06, 95% CI 0.01-0.25; P = 0.0001). Intensive care unit stay was not different (mean difference 0.99, 95% CI - 1.22 to 1.40; P = 0.53). One-year survival was better in the SU group (Peto OR 0.35, 95% CI 0.18-0.67; P = 0.001), as was the 2-year survival (Peto OR 0.38, 95% CI 0.17-0.86; P = 0.001). Conclusions Surgical aortic valve replacement using sutureless valves is associated with better early and mid-term outcomes compared with TAVI in high- or intermediate-risk patients.

The impact of sutureless prosthesis on the clinical outcome in minimally invasive aortic valve replacement is still unclear. We assessed mid-term outcomes of the sutureless and conventional valves implanted through right anterior minithoracotomy.Five hundred fifteen patients undergoing primary aortic valve replacement through a right anterior minithoracotomy (269 conventional versus 246 sutureless prostheses) between 2004 and 2014 were reviewed. The most common sutured prostheses were Carpentier-Edwards Perimount and Medtronic Mosaic, and the Sorin Perceval S mainly composed the sutureless prosthesis group. One hundred thirty-three pairs of patients were propensity matched and retrospectively analyzed.Cardiopulmonary bypass (p0.0001) and cross-clamping (p0.0001) times were shorter in the sutureless group (S group). We observed the same in-hospital mortality (1 versus 2; p=0.62) and incidence of postoperative stroke and pacemaker implant between the groups, but shorter duration of mechanical ventilation (6 versus 7 hours; p=0.001) in the S group. Generally, larger prostheses were implanted in the S group (p0.0001). Follow-up was longer (p0.0001) for sutured valves: 52 versus 15 months (overall median, 21 months). Overall Kaplan-Meier survival rate was 87.2% versus 97.0% (p=0.33) and 50% versus 100% (p=0.02) in elderly patients for sutured versus sutureless prostheses, respectively. Freedom from reoperation at follow-up (p=0.64) and transaortic gradients (12 versus 11 mm Hg; p=0.78) did not differ in the two groups.In the present limited cohort of patients, sutureless prostheses reduced operative times for aortic valve replacement and the duration of mechanically assisted ventilation and might have influenced early and mid-term survival. Larger studies are needed to confirm our data and compare long-term outcomes.

Background: Although benefitsof minimally invasive cardiac surgery have been described when compared with astandard approach through a median sternotomy, few experience and data exist inthe setting of double and triple valve surgery, whose annual incidence is 3% to25% of all valve surgery. We describe our experience with minimally invasivemultiple valve surgery through a right minithoracotomy. Methods: All patients scheduled for aminithoracotomy approach underwent a preoperative evaluation, includingcomputed tomography scan and epiaortic and femoral vessels ultrasound. Mitraland tricuspid valve disease is treated through a right minithoracotomy performedthrough a 4–5 cm lateral skin incision at the level of the fourth intercostalspace. In case of mitro-aortic or triple valve disease, the procedure iscarried out through a 5–7 cm incision in the 3rd intercostal space at 2–4 cmfrom the sternal edge. A femoral platform is generally used for cardiopulmonarybypass estabilishment, but, in selected patients, a central aortic cannulationcould be also performed to allow an antegrade perfusion. Results: We have started our minimally invasiveprogram in 2003. Gaining experience with the minithoracotomy, all patients witha concomitant mitral and tricuspid valve disease were treated with this kind ofapproach. In 1,604 patients undergoing minimally invasive mitral valve surgeryover a 10-year period, concomitant tricuspid valve repair was performed in 234patients (14.6 %), with good early and long-term outocomes. The next step,especially after the introduction of sutureless aortic prostheses, wasrepresented by the minimally invasive treatment of mitro-aortic and triplevalve disease. Sixty-nine patients underwent concomitant mitral and aorticvalve surgery through a right minithoracotomy, and a triple valve surgery wasperformed 12 (17.4%) of them. Good results were obtained in terms ofpostoperative mortality and morbidity. Conclusions: Double and triplevalve surgery through a right minithoracotomy is a feasible approach in thissubgroup of high-risk patients.

Objective Minimally invasive aortic valve surgery by way of a right anterior minithoracotomy has shown excellent results in terms of mortality, morbidities, and patient satisfaction. The aim of the present study was to compare minimally invasive aortic valve surgery by way of a right anterior minithoracotomy with conventional full sternotomy on early outcomes and midterm survival. Methods A retrospective, observational, cohort study was undertaken of prospectively collected data from 637 consecutive patients undergoing isolated aortic valve surgery from January 2005 to July 2010. Of the 637 patients, 192 (30%) underwent minimally invasive aortic valve surgery by way of a right anterior minithoracotomy. Of these, 138 patients (right anterior minithoracotomy group) were matched to a control group (full sternotomy group) using propensity score analysis. Results The baseline characteristics were similar in both groups. The overall in-hospital mortality was 0.7% (2/276), with no difference between the 2 groups. Minimally invasive aortic valve surgery by way of a right anterior minithoracotomy was associated with a lower incidence of postoperative atrial fibrillation (25 [18.1%] vs 41 [29.7%]; P = .003) and blood transfusions (26 [18.8%] vs 47 [34.1%]; P = .0006). In addition, patients in the right anterior minithoracotomy group had a shorter mechanical ventilation time (median, 6 vs 8 hours; P = .004) and postoperative length of stay (median, 5 vs 6 days; P = .02). The occurrence of stroke, renal failure, reexploration for bleeding, and wound infection was similar in both groups. At a median follow-up of 30 months (range, 17–54 months), survival was 96% ± 2% vs 88% ± 4% ( P = .3). Conclusions Right anterior minithoracotomy in patients undergoing isolated aortic valve surgery is associated with a lower incidence of postoperative atrial fibrillation and blood transfusion and shorter ventilation time and hospital length of stay. Prospective randomized trials are needed to confirm our data.

Mitral valve (MV) repair is the gold standard for the treatment of degenerative MV regurgitation. Recently, minimally invasive mitral valve surgery (MIMVS) has shown excellent postoperative outcomes compared with conventional surgery. The aim of our study is to report early and long-term outcomes of patients undergoing MIMVS through right mini-thoracotomy (RT) over an eight year period.From September 2003 to December 2011, a total of 1,604 consecutive patients underwent MIMVS through RT.The mean age was 62±13 years, 295 (42%) patients were female and 16 (2.3%) had previous cardiac operations. MV repair was successfully performed in 670 patients, with a rate of success of 95.3%. Repair techniques included annuloplasty (89%), leaflet resection (n=54.2%), neochordae implantation (12.1%), and sliding plasty (10.5%). Overall in-hospital mortality was 0.1%. Incidence of stroke was 1.3%. At eight-year follow-up, overall survival was 90.1%, freedom from reoperation 93%, and freedom from recurrent mitral regurgitation was 90%.MIMV repair through right minithoracotomy is a safe and reproducible procedure associated with high rate of MV repair, and excellent early postoperative and long-term results.

Aortic root replacement with porcine xenograft is a valuable treatment option in acute aortic dissection, but conduits are often prone to degeneration. Reoperation is still associated with high operative mortality, and it usually requires root removal and repetition of the Bentall procedure, or a less radical option limited to valve replacement. We describe two cases of Freestyle root degeneration in patients with chronic aortic dissection, in whom we performed a valve-in-valve procedure with the Perceval S prosthesis (Sorin Group, Saluggia, Italy).

OBJECTIVES - After a panel process, recommendations on the use of sutureless and rapid deployment valves in aortic valve replacement were given with special respect as an alternative to stented valves. METHODS - Thirty-one international experts in both sutureless, rapid deployment valves and stented bioprostheses constituted the panel. After a thorough literature review, evidence-based recommendations were rated in a three-step modified Delphi approach by the experts. RESULTS - Literature research could identify 67 clinical trials, 4 guidelines and 10 systematic reviews for detailed text analysis to obtain a total of 28 recommendations. After rating by the experts, 12 recommendations were identified and degree of consensus for each was determined. Proctoring and education are necessary for the introduction of sutureless valves on an institutional basis as well as for the individual training of surgeons. Sutureless and rapid deployment should be considered as the valve prosthesis of first choice for isolated procedures in patients with comorbidities, old age, delicate aortic wall conditions such as calcified root, porcelain aorta or prior implantation of aortic homograft and stentless valves as well as for concomitant procedures and small aortic roots to reduce cross-clamp time. Intraoperative transoesophageal echocardiography is highly recommended, and in case of right anterior thoracotomy, preoperative computer tomography is strongly recommended. Suitable annular sizes are 19–27 mm. There is a contraindication for bicuspid valves only for Type 0 and for annular abscess or destruction due to infective endocarditis. Careful but complete decalcification of the aortic root is recommended to avoid paravalvular leakage; extensive decalcification should be avoided not to create annular defects. Proximal anastomoses of concomitant coronary artery bypass grafting should be placed during a single aortic cross-clamp period or alternatively with careful side clamping. Available evidence suggests that the use of sutureless and rapid deployment valve is associated with (can translate into) reduced early complications such as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions and renal replacement therapy, respectively, and may result in reduced intensive care unit and hospital stay in comparison with traditional valves. CONCLUSION - The international experts recommend various benefits of sutureless and rapid deployment technology, which may represent a helpful tool in aortic valve replacement for patients requiring a biological valve. However, further evidence will be needed to reaffirm the benefit of sutureless and rapid deployment valves.

Background To report early and long-term outcomes of patients undergoing minimally invasive mitral valve surgery (MIMVS) through right mini-thoracotomy (RT) over a 10-year period. Methods From September 2003 to December 2013, a total of 1604 consecutive patients underwent MIMVS through RT. Results The mean age was 63 ± 13 years, 770 (48 %) patients were female and 218 (13.6 %) had previous cardiac operations. The most predominant pathology was degenerative disease (70 %), followed by functional mitral valve regurgitation (12 %), rheumatic disease (9.4 %), endocarditis (5 %) and prosthetic dysfunction (3.2 %). Mitral valve repair was performed in 1137 (71 %) patients and 476 (29 %) had mitral valve replacement. Direct aortic cannulation was achieved in 1325 (83 %) patients. Among patients with degenerative disease candidate for repair (n = 958), rate of mitral valve repair was 95 %. Repair techniques included annuloplasty (95 %), leafleat resection (63 %), neochordae implantation (16 %) and sliding plasty (11 %). Concomitant procedures included tricuspid valve repair (14.6 %), atrial fibrillation ablation (9.5 %) and atrial septal defect closure (3.2 %). Overall in-hospital mortality was 1.1 %. Thirty-four patients (2.1 %) had conversion to sternotomy. Incidence of stroke was 2 %. Overall survival at 10 years was 88 ± 2 %. Freedom from reoperation at 10 years was 94 ± 2 % for repair and 80 ± 6 % for replacement. Freedom from recurrent mitral regurgitation >3+ at 10 years was 90 ± 3 %. Conclusions Minimally invasive mitral valve surgery is a safe and reproducible approach associated with low mortality and morbidity, high rate of mitral valve repair and excellent late results.

We have previously shown that VEGF165 gene delivery into ischemic skeletal muscle exerts not only proangiogenic, but also remarkable antiapoptotic and proregenerative activity. The aim of this study was to determine whether recombinant adeno-associated virus (rAAV)-mediated gene delivery of VEGF165 into cardiac muscle, during acute myocardial infarction, exerts a protective effect to promote long-term functional recovery. Acute infarction of the anterior LV wall was induced in 12 chronically instrumented dogs by permanent occlusion of the LAD coronary artery. Four hours after occlusion, rAAV-VEGF165 or rAAV-LacZ (n=6 each; 5×10 12 viral particles per animal) was directly injected with an echo-guided needle into the dysfunctional cardiac wall. LV and arterial pressure, dP/dt max , and ejection fraction were not significantly different between the two groups over time. In contrast, in the infarcted region, at four weeks after infarction, fractional shortening was 75±18% and −3±15% of baseline and length-pressure area was 54±15% and 0.8±15% of baseline in VEGF165 versus LacZ, respectively ( P P

A 68-year-old woman with a 2-year history of dyspnea and fatigue was admitted to our hospital with a massive pericardial effusion. Computed tomography and cardiovascular magnetic resonance imaging revealed a huge (17 cm maximum diameter) intrapericardial mass. After successful tumor resection, a giant solitary fibrous tumour of the epicardium was diagnosed by histology. Histologic features of malignancy were absent, and the patient is alive and well 1 year after the operation, undergoing close follow-up at regular intervals. Recurrences have been exceptionally reported in benign solitary fibrous tumors, and experience with this exceptionally rare and enigmatic cardiac tumor is lacking.

Few experiences exist in minimally invasive cardiac surgery for the treatment of double-valve disease. We report our early experience in 69 patients, describing postoperative results. The introduction of sutureless aortic prostheses has implemented this treatment option, with a significant reduction of cardiopulmonary bypass and cross-clamp times.

Aims of the study: In this prospective, randomized study, we investigate the potential advantages of vacuum-assisted venous drainage (VAVD), compared to gravitational drainage (GD), in patients undergoing first-time coronary artery bypass graft (CABG) surgery, concerning biochemical markers of organ and blood cell damage. Materials and methods: Seventy-two consecutive patients were randomized into two groups [‘Vacuum’ (VAVD) n= 36; ‘Not vacuum’ (GD) n= 36]. VAVD was achieved using a wall vacuum source and with a suction regulator connected to the vent port of the hardshell venous reservoir. In the VAVD group, we used 28-French venous cannulas, and 36-French in the GD group. In the VAVD group, we measured arterial perfusion flow (APF) and the venous reservoir volume (VRV) with and without vacuum application just after starting extracorporeal circulation (ECC). Six blood samples were drawn at different times before, during and after ECC. Routine blood tests were performed to evaluate hemolysis, and hepatic and renal function. Results: The two groups were similar in terms of preoperative and operative characteristics. There were no significant differences in biochemical markers of organ function or hemolysis between the two groups. In the VAVD patients, platelet count was higher at 24 h after the end of the operation (VAVD 151.77± 50.28 μl versus Not vacuum 124.93± 41.60 μl, p= 0.028). With the narrower venous cannulas (28-French), only VAVD achieved a satisfactory APF (VAVD 2.35± 0.38 l/min/m2 versus GD 1.88± 0.27 l/min/m2, p= 0.002), with a larger VRV (VAVD 1091.67± 421 ml versus GD 808.33± 284.31 ml, p= 0.025). Conclusion: Vacuum-assisted venous drainage is a technique comparable to gravitational drainage with regard to hemolysis and organ perfusion. It allows better perfusion flow and heart decompression with smaller venous cannulas. This study suggests reduced platelet consumption with VAVD.

OBJECTIVES: Triple valve surgery (TVS) is still a challenge for surgeons because of prolonged cardiopulmonary bypass (CPB) and myocardial ischaemic times. The reported operative mortality rate for TVS ranges between 2.5 and 25%; long-term survival is also diminished, with reported survival rates at 5 and 10 years of 75–82 and 61–75%, respectively. The objective of our study is to define early and late clinical outcomes, reporting the initial experience in the treatment of triple valve disease through a minimally invasive approach. METHODS: A retrospective, observational, cohort study was undertaken of prospectively collected data on 106 patients who underwent TVS at our institution between October 2001 and June 2013. A total of 101 procedures were done through the standard median sternotomy; however, in 5 patients, the surgical procedure was carried out through a right minithoracotomy. Univariate analysis was performed to identify predictors of early and late survival. RESULTS: The in-hospital mortality rate was 5.6% (6 of 107 patients). Predictors of early mortality were: previous cardiac surgery [odds ratio (OR) 4, 95% confidence interval (CI) 1.08–5.2, P= 0.04], preoperative left ventricular ejection fraction (LVEF) (OR 0.9, 95% CI 0.8–1.1, P= 0.003), prolonged CPB time (OR 1.02, 95% CI 1.01–1.04, P= 0.01) and postoperative pulmonary complications (OR 8, 95% CI 5.8–41, P= 0.0001). Five- and 10-year survival rates were 85 ± 3 and 65 ± 9%, respectively. In univariate analysis, diabetes [hazard ratio (HR) 2.5, 95% CI 1–6.2, P= 0.045], preoperative dialysis (HR 3, 95% CI 2–4.7, P= 0.001), unstable angina (HR 4.8, 95% CI 1–18, P= 0.03), preoperative LVEF (HR 0.9, 95% CI 0.8–1.1, P= 0.02), concomitant coronary artery bypass grafting (CABG) (HR 2.5, 95% CI 1.5–5.7, P= 0.006), prolonged CPB time (HR 1.02, 95% CI 1.01–1.13, P= 0.006), postoperative pacemaker (PMK) implantation (HR 6.2, 95% CI 1.3–18, P= 0.01) and postoperative pulmonary complications (HR 3.3, 95% CI 2.1–7.3, P= 0.002) were found to be significant predictors of late mortality following TVS. The freedom rates from valve-related complications and reoperation at 10 years were 95 ± 2 and 97 ± 2%, respectively. The 10-year freedom rates from thromboembolism and anticoagulation-related haemorrhage were 88 ± 5 and 88 ± 4%, respectively. CONCLUSIONS: TVS offers encouraging short-term and long-term patient survival; these good results after TVS in patients with advanced valvular heart disease justify aggressive surgical therapy in these patients. TVS with a minimally invasive approach is feasible and could be another treatment option.

Background Many new, less invasive strategies are proposed for aortic valve operation in elderly patients. Rapid deployment sutureless aortic valve prosthesis has been recently introduced. We analyzed our experience with a sutureless valve implanted through a minimally invasive approach. Methods A retrospective observational study with prospectively registered data was conducted on 137 patients undergoing aortic valve replacement through a right anterior minithoracotomy. Between April 2011 and January 2013, 137 consecutive patients underwent aortic valve replacement with a recently introduced, rapid deployment, sutureless pericardial valve in minithoracotomy access (47 men; mean age, 76.6 ± 7.1 years). There were 35 obese patients with a body mass index of more than 30 kg/m 2 . Mean logistic EuroSCORE I was 10.0; 74 (54%) patients were in New York Heart Association functional class III and IV. In all, 19 (13.9%), 45 (32.8%), and 73 (53.3%) patients received 21-, 23-, and 25-mm valve prostheses, respectively. Results The mean aortic cross-clamp and cardiopulmonary bypass times were 59.3 ± 19 min and 92.3 ± 27 min, respectively. No operative mortality occurred. Median stay in the intensive care unit was 1 day, with assisted ventilation necessary for a median of 6 hours. Three cases of postoperative ischemic stroke were observed (1 patient with a previous history of an ischemic cerebral event). Median hospital length of stay was 6 days. Conclusions A sutureless valve for minimally invasive aortic valve replacement is a feasible, effective, and safe tool. Ultimately amplifying indications for less invasive aortic valve replacement in a high surgical risk subset of patients, it can become a valid alternative for transcatheter aortic valve implantation.

Objective Our objective was to compare off-pump coronary artery bypass surgery carried out via a left anterolateral thoracotomy (ThoraCAB) or via a conventional median sternotomy (OPCAB). Background Recent advances in minimally invasive cardiac surgery have extended the technique to allow complete surgical revascularization on the beating heart via thoracotomy. Methods Patients undergoing nonemergency primary surgery were enrolled between February 2007 and September 2009 at 2 centers. The primary outcome was the time from surgery to fitness for hospital discharge as defined by objective criteria. Results A total of 93 patients were randomized to off-pump coronary artery bypass surgery via a median sternotomy (OPCAB) and 91 to off-pump coronary artery bypass surgery via a left anterolateral thoracotomy (ThoraCAB). The surgery was longer for patients in the ThoraCAB group (median, 4.1 vs 3.3 hours) and there were fewer with more than 3 grafts (2% vs 17%). The median time from surgery to fitness for discharge was 6 days (interquartile range, 4-7) in the ThoraCAB group versus 5 days (interquartile range, 4-7) in the OPCAB group ( P = .53). The intubation time was shorter, by on average 65 minutes, in the ThoraCAB group ( P = .017), although the time in intensive care was similar ( P = .91). Pain scores were similar ( P = .97), but more analgesia was required in the ThoraCAB group (median duration, 38.8 vs 35.5 hours, P P = .024). ThoraCAB was associated with significantly worse lung function at discharge (average difference, −0.25 L, P = .01) but quality of life scores at 3 and 12 months were similar ( P = .52). The average total cost was 10% higher with ThoraCAB ( P = .007). Conclusions ThoraCAB resulted in no overall clinical benefit relative to OPCAB.

From early experience in cardiac surgery on the mitral valve, access was gained in different ways: through left and right antero-lateral extended thoracotomy for closed and correspondingly for open mitral commissurotomy, from right parasternal access with rib resection, and via median sternotomy. Median sternotomy remains the most common approach for mitral valve procedures, such as replacement or repair, allowing good visualisation, exposure and working field. Applying the largely spread access as median sternotomy, surgeons always wanted to overcome the necessity of large incisions, get a better surgical view, to dissect with better respect to structural integrity and have better aesthetic results. Enhanced understanding of surgical bases and technological development sourced a breakthrough in minimally-invasive approach for mitral valve surgery, offering several advantages such as less postoperative pain, lower morbidity and mortality, faster recovery and shorter hospital stay. In an effort to share the institutional experience in less invasive surgery, this article demonstrates our approach in mitral valve repair through a right minithoracotomy in the 3rd or 4th intercostal space.

Background Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis of unknown etiology and poor prognosis. The disease is characterized by the accumulation of foamy CD68+ histiocytes in bones and soft tissues, leading to the development of protean clinical manifestations (1,2). Two distinct but possibly interconnected pathogenic events have been described: an uncontrolled chronic inflammation inside the lesions (3) and the occurrence of an oncogenic BRAFV600E mutation in histiocytes (4). Interferon-a is considered the first line therapy for ECD, but its efficacy varies according to sites of disease involvement. Alternative therapeutic approaches, based on cytokine- (anakinra, infliximab, tocilizumab) (5) or BRAFV600E- (vemurafenib) targeting are currently under investigation. The assessment of drug efficacy in ECD, however, is hampered by both the extreme rarity of the disease, and the lack of suitable in vitro or in vivo models. 3-D tissue culture systems are emerging as an invaluable tool for drug testing. In particular, the Rotary cell culture system (RCCS™) bioreactor allows for 3-D dynamic culture of samples by optimizing mass and gas transfer. Indeed, we have recently validated the system for long-term (up to 15 days) culture of normal and pathological human tissues, showing the maintenance of viability and histo-architecture of cultured biopsies, as well as the feasibility to assess the impact of drugs (6). Objectives The aim of the study was to set up a preclinical model for drug testing for ECD, taking advantage of a 3-D dynamic culture of ex vivo biopsies in the RCCS™ bioreactor. Methods To assess and compare the efficacy of vemurafenib, infliximab and tocilizumab on ECD lesions, we obtained 4 contiguous tissue fragments from ECD biopsies and kept them in parallel cultures in bioreactor in the presence of each drug. We then evaluated the release of pro-inflammatory cytokines, metalloproteinases and necrosis markers through Bio-Plex Multiple-Cytokine Assays, zymography and G6PD determination in 48-hrs culture supernatants. Results As compared to the untreated sample, infliximab treatment determined a marked decrease in cytokine release and an anti-parallel increase of necrosis markers, supporting apoptosis induction in histiocytes. Tocilizumab induced massive mobilization of macrophages from the biopsy into the supernatant, but no cellular toxicity. The effects of vemurafenib were instead unremarkable, possibly due to the negligible fraction of BRAF-mutated histiocytes inside the lesions. Conclusions The RCCS™ bioreactor system is a well-suited tool for preclinical drug testing in ECD and allows both to compare the efficacy of drugs and to recapitulate their in situ mechanisms of action. This system can be further exploited as a tool to predict the impact of different therapeutic approaches in individual ECD patients. References Haroche et al, Rheum Dis Clin North Am. 2013;39(2):299-311 Cavalli et al, Ann Rheum Dis. 2013;72(10):1691-5. Stoppacciaro et al, Arthritis Rheum. 2006;54(12):4018-22 Haroche et al, Blood. 2012;120(13):2700-3. Dagna et al, J Clin Oncol. 2012;30(28):e286-90 Ferrarini et al, PLoS One. 2013;8(8):e71613. Acknowledgements We thank dr Luca Genovese and dr Massimo Alfano for the invaluable help in the assessment of supernatants9 cell viability. This work was supported in part by the Italian Ministry of Health (GR-2009-1594586 to LD). Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4223

Background Erdheim-Chester disease (ECD) is a rare, systemic disorder of unknown etiology, characterized by tissue infiltration with CD68+, CD1a- foamy histiocytes. ECD is still a chronically debilitating disease without a gold-standard treatment. Evidence is accumulating that inflammatory cytokines and chemokines are responsible for histiocytes recruitment and activation. In particular, recent data showed that IL-6 is strongly expressed in ECD lesions and increased serum levels of IL-6 have been implicated in the systemic manifestations observed in ECD. Objectives We intend to assess the efficacy and safety of IL-6 blockade in patients with ECD. Methods We are conducting an open-label, single-arm, phase II, prospective, pilot study of tocilizumab (TCZ) in ECD (ClinicalTrials.gov NCT01727206; Eudra-CT 2012-003151-11). We planned to treat 6 patients (with contraindications or unresponsive to IFN-α) with the IL-6 receptor inhibitor TCZ 8 mg/kg monthly. We are collecting clinical, laboratory and radiological data, by means of total-body computed tomography (CT) scan, Technetium-99m methylene diphosphonate (99mTc-MDP) bone-scan, fluorine-18-2-fluoro-d-glucose positron emission tomography (FDG-PET), brain and cardiac Magnetic Resonance Imaging (MRI). We are also evaluating the levels of pro-inflammatory cytokines and chemokines before, during and after therapy, in order to evaluate the network of soluble factors shown to be involved in ECD pathogenesis and its possible modulation after TCZ treatment. The Mann-Whitney U test for unpaired was chosen to compare data obtained from ECD patients and controls. The significance level was set at 0.05 (two-tailed p distribution). Results We present data from per protocol interim analysis on the first three patients who completed the protocol so far. All patients achieved significant improvement of all the clinical manifestations and laboratory findings (follow up at 12 months). Repeated whole-body CT scans, FDG-PET imaging and 99mTc-MDP bone scans confirmed the clinical and biochemical improvement in all patients. Cardiac MRI of the patient who had cardiovascular involvement showed an improvement of the diastolic function. However, the single patient who had CNS involvement had neurological progression, albeit showing improvement of other disease sites. During follow-up, we demonstrated a progressive reduction of circulating pro-inflammatory cyto-chemokines levels found to be increased before treatment. Plasma levels of IL-6 increased in all patients after the first infusion, as already shown in patients with other diseases treated with TCZ. Conclusions Although these data must be completed with the final analysis and possibly by larger studies, the interim analysis of the trial support the efficacy and safety of IL-6 targeting with TCZ in ECD patients, in particular when CNS is not involved. Of interest, TCZ showed beneficial effects on ECD cardiovascular involvement, which has been shown to be poorly responsive to most currently available treatments. References Stoppacciaro A et al. Arthritis Rheum. 2006 Dec;54(12):4018-22. Dagna L et al. Rheumatology (Oxford). 2010 Jun;49(6):1203-6. Mossetti G et al. Clin Exp Rheumatol. 2003 Mar-Apr;21(2):232-6. Arnaud L et al. Blood. 2011 Mar 10;117(10):2778-82. doi: 10.1182/blood-2010-06-294108. Acknowledgements This work was supported by a research grant from the Italian Ministry of Health to Lorenzo Dagna (GR-2009-1594586). Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5705

Background: Aortic valve replacement is a routine procedure with acceptable risk, but in some cases, such risk can justify contraindication. Transcatheter aortic valve implantation has emerged as an alternative with lower morbidity and mortality. Diverse prostheses are under current investigation. The aim of this study was clinical, safety and efficacy assessment using the Braile Inovare Prosthesis, produced in Brazil. Methods: Between June 2008 and september 2013, one hundred high risk or inoperable patients underwent transcatheter balloon expandable aortic valve implantation. The mean Logistic EuroSCORE was 37,36%. Fifteen patients presented with dysfunctional bioprostheses, and the remaining patients presented calcified aortic stenosis. The procedures were performed mostly in a hybrid operation room, under fluoroscopic and echocardiography guidance. Using a left minithoracotomy, the prostheses were implanted through the ventricular apexunder rapid ventricular pacing. Echocardiograph and angiograph controls were included. Results: Implantation was feasible in 97 cases. There was only two cases of operative mortality, and the 30-day mortality was 13%. The median transvalvular aortic gradient reduced from 44.8 15.3 to 14.1 8.0 mmHg. Left ventricular function improved in the first seven post-operative days. Paravalvular aortic regurgitation was present in 28,5% of cases, mostly trace. One case presented major vascular complication, and there were two cases of definite pacemaker implants. Two major stroke cases occurred. Conclusion: Transcatheter aortic valve replacement using the Braile Inovare Prosthesis is capable of providing encouraging results with increased functional and structural cardiac improvement. It is mandatory to continue follow-up to measure the benefit, complications and improved selection criteria.

Top of pageAbstract We have previously found that the delivery of the VEGF165 cDNA into skeletal muscle using AAV vectors, not only stimulates angiogenesis and arteriogenesis, but also exerts a remarkable anti-apoptotic and pro-regenerative activity during severe ischemic injury. Based on these observations, the aim of the present study was to test whether rAAV-VEGF165 delivery into cardiac tissue, during the acute phase of myocardial infarction, exerts a protective effect on the injured myocardium and promotes long-term functional recovery. Acute infarction of the anterior LV wall was induced in twelve chronically instrumented dogs by permanent occlusion of the LAD coronary artery. Four hours after occlusion, using an echo-guided needle, we injected rAAV-VEGF (n= 6; 4x1012 viral particles per animal) or rAAV-LacZ (n=6) directly into the paradoxical segment. Hemodynamics, echocardiographic data and segmental shortening of the infarcted region were measured at baseline (pre-occlusion) and monitored repeatedly during the subsequent four weeks. Histological analysis was performed at the end of the study. LV and arterial systolic and mean pressure, LV dP/dtmax and ejection fraction were not significantly different between the two groups over time. In contrast, the indexes of contraction of the infarcted area displayed marked differences after the second week post-infarction: at four weeks, the fractional shortening was 75 |[plusmn]|18% and |[minus]|3 |[plusmn]|15% of baseline and regional shortening work was 54 |[plusmn]|15% and 0.8 |[plusmn]|15% of baseline in rAAV-VEGF165 vs. LacZ group, respectively (P

Background Erdheim-Chester disease (ECD) is a rare form of systemic non-Langerhans histiocytoses of unknown aetiology. IFN-α is the first-line therapy, but its efficacy varies according to sites of disease involvement. When the cardiovascular or central nervous systems are involved, IFN-α treatment is scarcely effective and the prognosis is extremely poor. Evidence is accumulating that inflammatory cytokines and chemokines are responsible for histiocyte recruitment and accumulation inside ECD lesions. Objectives We evaluated the levels of TNF-α, interleukin (IL)-1b, IL-6, CCL2, CCL4, CCL5, CXCL8, CXCL10, and of the TNF-α soluble receptor-I and -II (which are bona fide markers of TNF-α activation) in ten patients with ECD and in healthy controls. We then treated two patients with cardiovascular ECD who were ineligible or unresponsive to IFN-α treatment with the anti-TNF-α neutralizing antibody infliximab, with a follow-up of 28 and 10 months, respectively. Methods Plasma levels of cytokines and chemokines were determined by Bio-Plex Multiple Cytokine Assay. sTNF-RI and sTNF-RII levels were assessed byELISA. Two independent sample permutation tests were performed to compare data obtained from ECD patients and controls. Unilateral alternatives were specified and examined. The significance level was chosen to be 0.05. Logistic regression was used to predict the group membership of a new case-patient. Results Patients with ECD had significantly increased plasma levels of TNF-α, soluble TNF-receptors, and TNF-regulated factors (IL-1b, IL-6, CCL2, and CCL5), as compared to healthy individuals. During follow-up, both treated patients showed a progressive reduction in the levels of circulating pathogenic cyto-chemokines and sTNF-Rs as well as improvement of symptoms, cardiac involvement and function. The treatment wasn’t associated to any significant side effect. Conclusions Overall our data indicate that TNF-α may have a key role in the pathogenesis of ECD and that TNF-α targeting could represent an effective therapeutic strategy for the disease. References Haroche J et al. Variability in the efficacy of interferon-alpha in Erdheim-Chester disease by patient and site of involvement: results in eight patients. Arthritis and rheumatism 2006 Haroche J et al. Cardiovascular involvement, an overlooked feature of Erdheim-Chester disease: report of 6 new cases and a literature review. Medicine 2004 Stoppacciaro A et al. Immunohistochemical evidence of a cytokine and chemokine network in three patients with Erdheim-Chester disease: implications for pathogenesis. Arthritis and rheumatism 2006 Dagna L et al. Erdheim-Chester disease: report on a case and new insights on its immunopathogenesis. Rheumatology 2010 Arnaud L et al. Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: a single-center series of 37 patients. Blood 2011 Disclosure of Interest None Declared

Objective To compare the outcomes of right minithoracotomy (RT) versus ministernotomy (MS) in patients undergoing minimally invasive aortic valve replacement (AVR). Methods From January 2005 to December 2011, 406 patients underwent minimally invasive AVR, of whom 251 patients were in the RT group and 155 were in the MS group. Results The overall in-hospital mortality was 1.2% with no difference between the 2 groups (1.2% in RT vs 1.3% in MS). Patients undergoing minimally invasive AVR using RT had a lower incidence of postoperative atrial fibrillation (19.5% vs 34.2%, P = .01), shorter ventilation time (median, 7 vs 8 hours; interquartile range, 5-9 vs 6-12 hours, P = .003), intensive care unit stay (median 1 vs 1 day; interquartile range, 1-1 vs 1-2 days; P = .001), and hospital stay (median, 5 vs 6 days; interquartile range, 5-6 vs 5-8 days; P = .0001). No difference was found in terms of cardiopulmonary time, crossclamping time, postoperative stroke, re-exploration for bleeding, or blood transfusion. Conclusions Minimally invasive AVR using RT was associated with lower postoperative morbidities and a shorter hospital stay than MS.