Myocardial transcriptomic analysis of diabetic patients with aortic stenosis: key role for mitochondrial calcium signaling.

BACKGROUND: Type 2 diabetes (T2D) is a frequent comorbidity encountered in patients with severe aortic stenosis (AS), leading to an adverse left ventricular (LV) remodeling and dysfunction. Metabolic alterations have been suggested as contributors of the deleterious effect of T2D on LV remodeling and function in patients with severe AS, but so far, the underlying mechanisms remain unclear. Mitochondria play a central role in the regulation of cardiac energy metabolism. OBJECTIVES: We aimed to explore the mitochondrial alterations associated with the deleterious effect of T2D on LV remodeling and function in patients with AS, preserved ejection fraction, and no additional heart disease. METHODS: We combined an in-depth clinical, biological and echocardiography phenotype of patients with severe AS, with (n = 34) or without (n = 50) T2D, referred for a valve replacement, with transcriptomic and histological analyses of an intra-operative myocardial LV biopsy. RESULTS: T2D patients had similar AS severity but displayed worse cardiac remodeling, systolic and diastolic function than non-diabetics. RNAseq analysis identified 1029 significantly differentially expressed genes. Functional enrichment analysis revealed several T2D-specific upregulated pathways despite comorbidity adjustment, gathering regulation of inflammation, extracellular matrix organization, endothelial function/angiogenesis, and adaptation to cardiac hypertrophy. Downregulated gene sets independently associated with T2D were related to mitochondrial respiratory chain organization/function and mitochondrial organization. Generation of causal networks suggested a reduced Ca2+ signaling up to the mitochondria, with the measured gene remodeling of the mitochondrial Ca2+ uniporter in favor of enhanced uptake. Histological analyses supported a greater cardiomyocyte hypertrophy and a decreased proximity between the mitochondrial VDAC porin and the reticular IP3-receptor in T2D. CONCLUSIONS: Our data support a crucial role for mitochondrial Ca2+ signaling in T2D-induced cardiac dysfunction in severe AS patients, from a structural reticulum-mitochondria Ca2+ uncoupling to a mitochondrial gene remodeling. Thus, our findings open a new therapeutic avenue to be tested in animal models and further human cardiac biopsies in order to propose new treatments for T2D patients suffering from AS. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique Identifier: NCT01862237.

Totally endoscopic non-robotic excision of aortic valve fibroelastoma: a case report.

BACKGROUND: Papillary fibroelastomas (PFEs) are a rare subtype of benign primary cardiac tumours, which are most commonly found on the aortic valve. Although median sternotomy is still used frequently there has been different attempts to remove the aortic valve PFEs minimally invasively using robotic and Mini sternotomy approach. CASE PRESENTATION: We report herein a case of totally endoscopic non robotic removal of PFE of aortic valve. CONCLUSIONS: The encouraging intra and post-operative outcomes and fast recovery using totally endoscopic approach for removal of PFE shows the potential benefits of this technique.

Early Clinical Experiences of Robotic Assisted Aortic Valve Replacement for Aortic Valve Stenosis with Sutureless Aortic Valve.

Robotic assisted aortic valve surgery is still challenging and debatable. We retrospectively reviewed our cases of robotic assisted aortic valve replacement utilizing sutureless aortic valve with following surgical technique: 3 ports, 1 for endoscope and 2 for the robotic arms were inserted in the right chest and da Vinci Si robotic system (Intuitive Surgical, Sunnyvale, CA, USA) was adapted to these ports. Cardiopulmonary bypass was initiated through peripheral cannulations. A vent cannula was placed through the right superior pulmonary vein and a cardioplegia cannula in the ascending aorta. After cardioplegic arrest following aortic cross-clamp, the aortic valve was exposed through a clam shell aortotomy. Valvectomy along with decalcification was performed. Next using 3 guiding sutures the Perceval S valve (LivaNova, London, UK) was parachuted down and deployed. After confirming valve position, the aortotomy was closed. There were no major complications during the procedures and no conversion to sternotomy. Exposure of aortic valve was of high quality. Valvectomy required assistance with long scissors by the bedside surgeon for excision of the severely calcified valve cusps and effective decalcification of annulus. Postoperative convalescence was uncomplicated except for postoperative atrial fibrillation in 1 patient. Robotic assistance in aortic valve procedure enabled excellent exposure of the aortic valve and improved manipulation and suturing of the aortic annulus and aorta. There needs to be improvement of instrumentation for valve debridement and removal of calcium from the annulus. In addition, the sutureless valve technology contributes to the feasibility and the efficacy of this procedure.

Minithoracotomy and Beating Heart Strategy for Mitral Surgery in Secondary Mitral Regurgitation.

BACKGROUND: In patients with secondary mitral regurgitation (MR) associated with low ejection fraction or previous heart surgery, minimally invasive mitral valve surgery without aortic cross-clamp (MIMVS-WAC) has shown promising results. We report our experience for this strategy in our centers. METHODS: Between August 2011 and April 2017, 46 patients (mean age 69 ± 11 years, 76% males) received MIMVS-WAC. Indications for this technique were prior coronary bypass surgery (26%), severe or recent left ventricular (LV) dysfunction (30%), or both (39%). The mean EuroSCORE II was 12 ± 10. RESULTS: For each procedure, we conducted right minithoracotomy and hypothermic cardiopulmonary bypass (CPB) after peripheral cannulation. Mean CPB time was 159 ± 39 minutes. A mitral valve replacement (MVR) was performed in 23 cases (50%), an annuloplasty in 22 cases (48%), and a prosthesis pannus removal in 1 case (2%). Mean hospital length of stay was 12 ± 5.4 days. We report no sternotomy conversions, six reoperations for bleeding, and three deaths at 30 days. Transfusion was requested in 62% (mean infusion 2 ± 2.4 packed red blood cells). The postoperative echocardiography showed an LV function preservation in 69% of cases and a reduction of pulmonary arterial pressure in 73% of cases. Four additional deaths occurred in the long-term follow-up (mean 637 ± 381 days, median 593 days). No mitral reoperation was required, with a MR ≤ 2 in 90% of patients. CONCLUSION: In high-risk patients, the MIMVS-WAC is a safe technique. It avoids hard dissections while ensuring excellent preservation of cardiac function.

Quality of Life After Cardiac Operations Based on the Minimal Clinically Important Difference Concept.

BACKGROUND: Health-related quality of life (HRQOL) is an increasingly important issue in assessing the consequences of any surgical or medical intervention. Our study aimed to evaluate change in HRQOL 6 months after elective cardiac operations and to identify specific predictors of poor HRQOL. METHODS: In this prospective, single-center study, HRQOL was evaluated before and 6 months after the operation using the Medical Outcome Study 36-Item Short Form Health Survey questionnaire and its two components: the Physical Component Summary and the Mental Component Summary. We distinguished patients with worsening of HRQOL according to the minimal clinically important difference. All consecutive adult patients undergoing cardiac operations were included. RESULTS: The preoperative and postoperative 36-Item Short Form Health Survey questionnaires were completed by 326 patients, and 24 patients died before completing follow-up questionnaires. On the basis of the definition used, clinically significant deterioration of HRQOL was observed in 93 patients (26.6%) for the Physical Component Summary and in 99 patients (28.2%) for the Mental Component Summary. Renal replacement for acute renal failure and mechanical ventilation for longer than 48 hours were independent risk factors for Physical Component Summary and Mental Component Summary worsening or death. CONCLUSIONS: Although our study showed overall improvement of quality of life after cardiac operations, more than one-quarter of the patients manifested deterioration of HRQOL at 6 months postoperatively. The findings from this study should help clinicians to inform patients about their likely postoperative functional status and quality of life.

Impact of very high pressure stent deployment on angiographic and long-term clinical outcomes in true coronary bifurcation lesions treated by the mini-crush stent technique: A single center experience.

BACKGROUND: Percutaneous coronary intervention (PCI) for bifurcation lesions (BL) using 2 stents technique is known to be associated with high rates of procedural failure especially on the side branch (SB) mainly due to stent incomplete apposition. Stent deployment at very high pressure (SDHP) may lead to better stent expansion and apposition. However, SDHP may also be at the origin of deeper wall injury resulting into major cardiac adverse events. No data are available on evaluation of SDHP in BL treated by a mini-crush stent technique. METHODS: One hundred and thirteen consecutive patients underwent PCI for BL (Medina 1, 1, 1) using a mini-crush stent technique with SDHP defined as ≥20atm. An angiographic follow-up was performed at 6 month and clinical follow-up was obtained at a median of 3 years. RESULTS: Stent deployment mean pressures were 20±1.4atm (range 20-25) in the main vessel (MV) and 20±1.5atm (range 20-25) in SB. Simultaneous final kissing balloon was used in 92% of cases. PCI was successful in 100%. Angiographic follow-up was obtained in 83% of patients. Restenosis rate was 13% (12% restenosis in the SB) with only one case (0.8%) of SB probable thrombosis. Another case of late stent thrombosis occurred at a 3 years clinical follow-up. CONCLUSION: Compared with previously published studies in which stents were deployed at lower pressure, SDHP does not increase the restenosis rate in BL using mini-crush stent technique but seems to reduce the rate of stent thrombosis.

Proof of Concept of an Endoscopic Sutureless Valve Sizer.

OBJECTIVE: In this paper, we present an endoscopic expandable sizer conceived to allow thoracoscopic aortic valve replacement with a sutureless prosthesis using a dynamic sizing of the aortic annulus. METHODS: Ten aortic torsos were prepared using a five-trocar thoracoscopic setting. Once the aortotomy was performed and the aortic valve leaflets removed, the technical feasibility of the endoscopic sizing (introduction into the trocar, expansion into the aortic annulus, determination of the valve size, and retraction) with the device was assessed. In case of successful thoracoscopic sizing, endoscopic implantation of a sutureless valve (five LivaNova Perceval prosthesis and five Medtronic 3f Enable bioprosthesis) was performed. Before ascending aorta closure, we assessed the appropriate sealing of the bioprosthesis in the native annulus with camera visualization and a nerve hook inspection. RESULTS: All the 10 endoscopic sizings were technically feasible. The scheduled aortic sutureless valve implantations were successfully performed. In all cases, fitting and placement of the sutureless bioprosthesis in the flaccid heart was satisfactory, with no paraprosthetic leakage detectable by the nerve hook. CONCLUSIONS: The use of the endoscopic expandable sizer is technically possible. In this early-stage test in the flaccid heart, selection of the valve size was satisfactory during thoracoscopic sutureless aortic bioprosthesis implantation. Further laboratory evaluation with fluid dynamics (aortic root pressurization) will be performed before a clinical study is started.

First in Human Totally Endoscopic Perceval Valve Implantation.

Totally endoscopic cardiac operations for coronary procedures and atrial septal defect repair have demonstrated improved quality of life, but they have required longer cross-clamp times compared with open operations. Although transcatheter valve implantation remains appropriate for inoperable patients, the totally endoscopic approach could be an effective treatment for lower risk patients, including complete removal of the stenotic aortic valve, while minimizing surgical chest wall trauma, and providing excellent early quality of life. Totally endoscopic aortic valve replacement procedures were previously performed with the 3f Enable bioprosthesis. We present the first case, to our knowledge, of Sorin Perceval implantation.

Mid-term results of mitral valve repair for ischemic mitral regurgitation with ETlogix ring: A single-center study.

BACKGROUND: Ischemic mitral regurgitation (IMR) is a common complication of coronary artery disease and represents an independent predictor of mortality. In the IMR the pattern of mitral valve annular dilatation is asymmetrical: this can explain the long-term incidence of recurrent mitral regurgitation after surgical annular size reduction with a symmetrical ring. The aim of this study is to analyze early and mid-term results of mitral valve repair (MVR) with the CMA IMR ETlogix ring, specifically developed for the surgical correction of IMR. METHODS: Retrospectively, we studied 157 consecutive patients who underwent MVR with the CMA ETlogix ring for the treatment of grade ≥2 IMR in our center between June 2006 and December 2012. We reported clinical and echocardiographic early and mid-term results of this surgical technique. RESULTS: Postoperative 30days mortality was 6.3%. Postoperative echocardiography evaluation at discharge revealed the absence of residual MR in 70%, mild MR in 26.5% and moderate MR in 3.5% of patients respectively. Median echographic follow-up time was 28 (3-84) months: survival rate was 92.1% at 32months; free from mitral valve reoperation rate was 97.5% and grade >2 MR recurrence free survival rate was 96.6%. CONCLUSION: There are a few reports in the literature concerning the mid-term results of IMR surgical correction with CMA Etlogix ring. Our study, taking into account a large series of patients and an important follow-up period, demonstrates the effectiveness of this surgical repair technique reporting a low mid-term incidence of recurrent MR.

Biaxial rupture properties of ascending thoracic aortic aneurysms.

UNLABELLED: Although hundreds of samples obtained from ascending thoracic aortic aneurysms (ATAA) of patients undergoing elective surgical repair have already been characterized biomechanically, their rupture properties were always derived from uniaxial tensile tests. Due to their bulge shape, ATAAs are stretched biaxially in vivo. In order to understand the biaxial rupture of ATAAs, our group developed a novel methodology based on bulge inflation and full-field optical measurements. The objective of the current paper is threefold. Firstly, we will review the failure properties (maximum stress, maximum stretch) obtained by bulge inflation testing on a cohort of 31 patients and compare them with failure properties obtained by uniaxial tension in a previously published study. Secondly, we will investigate the relationship between the failure properties and the age of patients, showing that patients below 55years of age display significantly higher strength. Thirdly, we will define a rupture risk based on the extensibility of the tissue and we will show that this rupture risk is strongly correlated with the physiological elastic modulus of the tissue independently of the age, ATAA diameter or the aortic valve phenotype of the patient. STATEMENT OF SIGNIFICANCE: Despite their medical importance, rupture properties of ascending thoracic aortic aneurysms (ATAA) subjected to biaxial tension were inexistent in the literature. In order to address this lack, our group developed a novel methodology based on bulge inflation and full-field optical measurements. Here we report rupture properties obtained with this methodology on 31 patients. It is shown for the first time that rupture occurs when the stretch applied to ATAAs reaches the maximum extensibility of the tissue and that this maximum extensibility correlates strongly with the elastic properties. The outcome is a better detection of at-risk individuals for elective surgical repair.

Unusual complication during a percutaneous coronary intervention for a bifurcation lesion using T and Protrusion technique.

Our case reports the first migration of a stent already deployed at high pressure in the main vessel during a 2-stent strategy for a bifurcation lesion using T and protrusion technique. The Kissing balloon was not optimal and could have led to an insufficient strut/cell opening and then to LAD stent pulled back into the artery tree. This case report highlights the importance of an optimal Kissing Balloon in two stent bifurcation technique.

Idiopathic Aortic Root to Right Atrial Fistula.

An aorta to right atrium fistula is rare. We report a case of idiopathic aortic root to right atrial fistula with right heart failure and review the literature. doi: 10.1111/jocs.12751 (J Card Surg 2016;31:373-375).

Closed chest human aortic valve removal and replacement: Technical feasibility and one year follow-up.

BACKGROUND: Minimally invasive aortic valve replacement has so far required a minithoracotomy or a ministernotomy. We present here the first series of totally endoscopic aortic valve replacement (TEAVR). METHODS: Between June 2013 and April 2015, 14 consecutive patients (12 males, mean age=76 ± 5.4 years) with a mean EuroSCORE II of 2.72 ± 0.03% underwent TEAVR. A five trocar setting was used in all patients: after ablation of the native valve, a Nitinol stented sutureless 3f Enable Medtronic valve, compressed into the main working trocar, was introduced into the thorax and then expanded in the aortic root. RESULTS: Among the 14 patients, a thoracoscopic approach was successful in 13 (92.8%) and conversion into an open surgery using the right anterior minithoracotomy was necessary to close the aortotomy in one case. Mean cross-clamping and cardiopulmonary (CPB) times were 112 ± 18 and 161 ± 31 min, respectively. All patients left the surgical unit within 8 days after the operation without any paravalvular leakage. There was no paravalvular regurgitation, conductive block or any major adverse event at a mean follow-up of 10 ± 4 months (range 2-16). CONCLUSIONS: TEAVR is feasible and safe in a selected subset of patients. Closed chest surgery has the potential to become the future approach of the isolated aortic valve replacement in low risk patients but further technical refinement and larger studies are necessary to reduce operative durations and enhance reproducibility.

High veno-arterial carbon dioxide gradient is not predictive of worst outcome after an elective cardiac surgery: a retrospective cohort study.

Alteration of tissue perfusion is a main contributor of organ dysfunction. In cardiac surgery, the importance of organ dysfunction is associated with worse outcome. Central venous-arterial difference in CO2 tension (ΔCO2) has been proposed as a global marker of the adequacy of tissue perfusion in shock states. We hypothesized that ΔCO2 could be increased in case of postoperative organ failure or worse outcome. In this monocentric retrospective cohort study, we retrieved, from our database, 220 consecutive patients admitted in intensive care after an elective cardiac surgery. Four time points were formed: ICU admission, and 6, 24 and 48 h after. A ΔCO2 below 6 mmHg defined the normal range values. The SOFA score, intensive care unit and hospital length of stay, hospital and 6-month mortality rate were recorded. We compared patient with low ΔCO2 (<6 mmHg) and high ΔCO2 (≥6 mmHg). We included 55 (25 %) and 165 patients in low and high ΔCO2 groups, respectively. The SOFA score, the hospital and 6 months mortality rate were higher in patients with low ΔCO2. Surprisingly, we did not find results previously published in other surgical settings. In cardiac surgery, ΔCO2 has a low predictive value of outcome.

Two Hundred Consecutive Implantations of the Sutureless 3f Enable Aortic Valve: What We Have Learned.

BACKGROUND: In this article we present a consecutive single-center experience of implantation of the Medtronic 3f Enable aortic valve (Medtronic Inc, Minneapolis, MN). METHODS: Between March 2011 and October 2014, 200 consecutive patients (mean age, 76.4 ± 5.9 years; logistic EuroScore, 7.8% ± 7.0%) in our unit received the 3f Enable valve. This is a retrospective analysis of this prospective monocentric cohort. RESULTS: The 3f Enable valve could be implanted in all the scheduled 141 isolated aortic valve replacement (AVR) procedures (14 full sternotomies, 73 ministernotomies, 44 minithoracotomies, and 10 thoracoscopic approaches) and 59 combined procedures (all using full sternotomy). Reclamping was necessary in 7 (3.5%) patients (paravalvular leakage [PVL] was ≥ grade 1 because of undersizing or prosthetic misalignment); mean cross-clamp and cardiopulmonary bypass (CPB) times were 65 ± 31 and 91 ± 39 minutes, respectively. Sixteen (8%) patients required early implantation of a pacemaker (PM). At a mean follow-up of 12.6 ± 8.1 months, mean transvalvular gradient and effective orifice area (EOA) were 9.8 ± 4.4 mm Hg and 1.87 ± 0.6 cm(2), respectively. Mild PVL was present in 7 (3.5%) patients and moderate PVL was present in 5 (2.5%) patients. No device migration was registered, and no moderate PVL was detected in the last 100 patients of the cohort. Overall, 3-year survival was 78%. CONCLUSIONS: The 3f Enable valve shows excellent results regarding PVL but in our experience required a learning curve and a refinement of the technique of implantation. Use of the prosthesis was possible in various less invasive approaches.

Sutureless aortic bioprosthesis valve implantation and bicuspid valve anatomy: an unsolved dilemma?

Interest is growing in the clinical use of sutureless (SU) valves. However, indications in some anatomical sub-settings, like bicuspid aortic valves (BAV), have been so far limited. We discuss herein our initial experience with the implantation of the 3f Enable SU bioprosthesis in patients with a BAV. Patients with a BAV were selected in our unit between March 2011 and September 2014 for a SU 3f Enable valve implantation. Twenty of the 198 patients who underwent a 3f Enable valve implantation in our unit had a BAV. Procedural success was 100 %, but reclamping was necessary in one (5 %) case. Median size of implanted bioprosthesis was 23 mm. After a mean follow-up of 13.8 ± 10.7 months, survival was 100 %. Two patients (10 %) showed an immediate grade 1 paravalvular leak (PVL) that progressed to grade 2 and 3+ (moderate/severe), respectively, during follow-up. Type of bicuspidy (Sievers classification) in these two patients was 0 and intraoperatively aortic annuli admitted the 25 mm calibrator. Among the 18 patients without PVL, no one had a type 0 large BAV. At 1 year, implantation of the 3f Enable SU bioprosthesis appears to be safe in patients with BAV type I and II, while in type 0 use of the SU valve seems to be safe only if the annular diameter is <25 mm. Larger studies are necessary to confirm our findings in order to clarify the indications for SU technology in the subset of bicuspid patients.