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.

Cardiopulmonary Bypass Blood Flow Rates and Major Adverse Kidney Events in Cardiac Surgery: A Propensity Score-adjusted Before-After Study.

OBJECTIVES: Cardiac surgery associated-acute kidney injury is a common and serious postoperative complication of cardiac surgery, which is associated with increased postoperative morbidity and mortality. This study aimed to explore the association between cardiopulmonary bypass (CPB) blood flow rate (BFR), and major adverse kidney events (MAKEs) at day 30. DESIGN: Retrospective single-center before-after observational study. Patients were divided in 2 groups according to CPB flow rates: a first group with an institutional protocol targeting a CPB-BFR of >2.2 L/min/m² (low CPB-BFR group), and a second group with a modified institutional protocol targeting a CPB-BFR of >2.4 L/min/m² (high CPB-BFR group). The primary outcome was MAKE at 30 days, defined as the composite of death, renal replacement therapy or persistent renal dysfunction. SETTING: The data were collected from clinical routines in university hospital. PARTICIPANTS: Adult patients who underwent elective and urgent cardiac surgery without severe chronic renal failure, for whom CPB duration was ≥90 minutes. INTERVENTIONS: We included 533 patients (low CPB-BFR group, n = 270; high CPB-BFR group, n = 263). MEASUREMENTS AND MAIN RESULTS: A significant decrease in MAKE at 30 days was observed in the high CPB-BFR group (3% v 8%; odds ratio [OR], 0.779; 95% confidence interval [CI], 0.661-0.919; p < 0.001) mainly mediated by a lower 30-day mortality in the high CPB-BFR group (1% v 5%; OR, 0.697; 95% CI, 0.595-0.817; p = 0.001), as was renal replacement therapy (1% v 4%; OR, 0.739; 95% CI, 0.604-0.904; p = 0.016). CONCLUSIONS: In patients undergoing cardiac surgery, increased CPB-BFR was associated with a decrease in MAKE at 30 days including mortality and renal replacement therapy.

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.

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.

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).

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.

Aortic sutureless bioprosthesis implantation following degeneration of a SOLO stentless valve.

A case is presented of the early degeneration of a 21 mm SOLO stentless valve concomitant with severe mitral regurgitation (MR). Transcatheter valve-in-valve implantation was considered in this high-risk case (logistic EuroSCORE 29.3%), but was dismissed because of the risk of coronary occlusion, an absence of visual landmarks, and the impossibility to treat the MR. Following the implantation of a 27 mm Medtronic Hancock II mitral bioprosthesis, the leaflets of the SOLO valve were removed, and a 19 mm 3f Enable sutureless bioprosthesis delivered into the remaining sewing belt of the stentless valve. The total cross-clamp time was 64 min. No aortic paravalvular leakage was detected at discharge and early follow up (four months); the mean and peak transvalvular aortic gradients were 13 and 23 mmHg, respectively, and the left ventricular ejection fraction 60%. A sutureless strategy simplified the management of this high-risk case.

Combined Minimally Invasive Redo Mitral Surgery and Pectus Excavatum Correction.

We present a technique of mitral valve surgery performed in a patient with severe pectus excavatum and previous Bentall surgery. Neither redo sternotomy nor conventional right minithoracotomy were thought to provide adequate surgical access to the mitral valve. We therefore opted for a combined procedure comprising sternal reconstruction and right minithoracotomy mitral valve replacement. The mitral valve was replaced and the sternum reconstructed according to the Ravitch technique.

Sutureless 3F Enable Valve Replacement for Pure Aortic Regurgitation.

BACKGROUND AND AIM: We present our experience in the use of the sutureless valve in patients undergoing aortic valve replacement for pure aortic regurgitation. METHODS: Out of 167 patients who underwent sutureless aortic valve implantation with a Medtronic 3f Enable prosthesis in our unit between March 2011 and February 2014, 12 (7.1%) received a sutureless valve for pure aortic regurgitation. RESULTS: Mean age, logistic EuroSCORE, and left ventricular ejection fraction were 72 ± 5 years, 6.3 ± 2.9%, and 52.5 ± 15.3%, respectively. The sutureless valve could be successfully implanted in all cases; nine patients had a full sternotomy (associated coronary artery bypass graft in four cases and associated mitral surgery in five), one patient had a ministernotomy, and two had a thoracoscopic approach. Average cross-clamping and cardiopulmonary bypass times were 90 ± 30 and 127 ± 51 minutes, respectively. At the outpatient echocardiography, average mean gradient was 10.54 ± 4.99 mmHg and a grade I-II paravalvular leakage (PVL) was detected in the first patient of the cohort (ministernotomy approach). At a mean follow-up of 11.1 ± 5.5 months, average mean gradient was 9.75 ± 2.87 mmHg, no new PVL was detected, and the known PVL was stable. No pacemaker implantation was required. CONCLUSIONS: Implantation of the 3f Enable sutureless valve is technically possible with pure aortic regurgitation in selected patients. Multicenter investigations are necessary to assess the mid-term benefits of such a device in this subset of patients.

Sutureless Valve Implantation in Sievers Type 0 Bicuspid Annuli: A Word of Caution.

AIM: We describe a series of 3f Enable sutureless prostheses implanted in bicuspid valves. METHODS: Between March 2011 and April 2014, five patients with Sievers type 0 bicuspid valves were selected to receive the sutureless 3f Enable prosthesis . Exclusion criteria were: intraoperative calibration of the aortic annulus >27 mm, left ventricle ejection fraction <50%, age <70 years. RESULTS: All the implantations could be performed without the necessity to re-deploy the prosthesis . The perioperative transesophageal echocardiogragram detected two moderate paravalvular leakages (PVL) in two patients who received a large size of prosthesis (25 and 27 mm, respectively). The two leakages, at a follow-up of 32 and 24 months, respectively, increased to grade II and II +. No PVL appeared in the other three patients. CONCLUSION: This experience should warn about the inadequate performance of the 3f Enable valve in Sievers type 0 large aortic bicuspid annuli. In this subset any minor intraoperative residual leakage should not be accepted.

Feasibility of sutureless valve implantation in reoperation for degenerated 19 mm aortic valvular bioprostheses.

BACKGROUND AND AIM OF THE STUDY: Transcatheter aortic valve implantation (TAVI) is a promising option to treat degenerated aortic valve bioprostheses, and may involve Valve-in-Valve (ViV) procedures. Unfortunately, the ViV technique may provide an inadequate relief of stenosis in small-diameter degenerated bioprostheses, especially in the 19 mm valve subgroup. The study aim was to determine the feasibility and reliability of reoperating 19 mm degenerated bioprostheses, using a minimally invasive sutureless valve implantation. METHODS: Between March and December 2012, three reoperative procedures for degenerated 19 mm conventional aortic bioprostheses were performed at the authors' unit. Stenosis was the main modality of structural deterioration. A partial upper ministernotomy approach was used, whereby part of the sewing ring of the previous bioprosthesis was left in place and a 19 mm Medtronic Enable sutureless valve was implanted in all cases. RESULTS: The average valve implantation time was 10.3 min. There were no cases of operative mortality or major morbidity. One permanent pacemaker was required. At discharge, transthoracic echocardiography showed no paravalvular leakages; the average transvalvular gradient was 16 mmHg. The one-year follow up showed no paravalvular leakages and unchanged gradients. CONCLUSION: The use of a surgical sutureless valve after explanting a 19 mm degenerated bioprosthesis is feasible and effective for relieving stenosis However, larger series are needed to confirm these preliminary results.

Video-assisted minithoracotomy approach: technical developments towards totally endoscopic sutureless aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: Interest in sutureless aortic bioprostheses is growing because of the potential advantages that such devices can bring in facilitating minimally invasive approaches. Video assistance can potentially enhance details of decalcification and sutureless valve sizing. We review the feasibility of sutureless aortic valve replacement (AVR) via a minimally invasive video-assisted (MIVA) right anterior minithoracotomy. METHODS: Between November 2012 and November 2013, 21 patients were selected to undergo an AVR using the Enable sutureless device (Medtronic, Minneapolis, MN, USA) via a video-assisted right second space minithoracotomy. RESULTS: Procedural success of the MIVA approach was 95.3% (one conversion to median sternotomy due to severe pleural adhesions). Average aortic clamp time was 72.1 ± 22.1 min. No paravalvular leakage was detected at discharge. Thirty-day mortality was 4.7% (one patient, pulmonary embolism). CONCLUSIONS: The described approach appears to be safe and feasible with adequate clamp times. Video assistance allows optimal visualization of the aortic root and accurate valve delivery, without conflict between the device, the camera, and the instruments, making this setting an encouraging baseline towards the assessment of the totally endoscopic approach.

Sutureless Medtronic 3f Enable aortic valve replacement in a heavily calcified aortic root.

The case is reported of a surgical aortic valvular stenosis with a severely calcified ascending aortic root in a 76-year-old woman. The morphology and size of the aortic annulus were unsuitable for transcatheter aortic valve implantation (TAVI); thus, surgery was scheduled. Aortic calcifications allowed a transverse aortotomy 4 cm superior to the sinotubular junction, with a remote endoaortic view of the valve. A Medtronic 3f Enable sutureless bioprosthesis was then implanted after aortic annular decalcification. Sutureless bioprostheses are new tools that promise to reduce technical difficulties and cross-clamp times in minimally invasive aortic valve replacement surgery. In addition, sutureless techniques may have other possible advantages in special circumstances requiring full sternotomy access, such as in the present case.

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.

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.

Incidental disclosure of asymptomatic coronary embolic occlusion related to mitral valve papillary fibroelastoma: an unusual finding and a review of the literature.

Cardiac papillary fibroelastoma (CPF) located on mitral and aortic valves are known to produce systemic embolism mainly represented by strokes, whereas myocardial infarction and sudden death usually result from specific locations around LVOT. Coronary artery embolic occlusion originating from a mitral location has not yet been reported. The case is reported of a 42-year-old man referred for surgical treatment of a mitral valve papillary fibroelastoma disclosed after transitory and completely regressive left hemicorporeal deficiency and previous myocardial infarct. Due to the left chamber location, surgery was scheduled and complete removal of the mass achieved. These findings emphasize the potential life-threatening complications of CPF and, independent of risk factors, the need to perform systematic coronary angiography before surgical excision is considered.

Current hospital mortality of aortic valve replacement in octogenarians.

BACKGROUND AND AIM OF THE STUDY: The increasing incidence of cardiovascular disease with age, coupled to a constant extension of life expectancy in industrialized countries, is leading to an ever-increasing number of elderly patients being referred for aortic valve replacement (AVR). In light of advances in surgical technology and cardiac protection, the operative mortality and risk factors have been updated in order to specify surgical indications. METHODS: Between January 2000 and December 2004, a total of 442 patients (203 males, 239 females) aged > or =80 years (mean age 82.7 +/- 2.3 years) underwent AVR at the authors' institution. Surgery was either isolated (n = 344) or associated with coronary revascularization (n = 86), mitral valvuloplasty (n = 5) or aortic surgery (n = 7). Seventeen patients had undergone previous cardiac surgery. The EuroScore was calculated for each patient. RESULTS: Overall operative mortality was 7.5% (n = 33). Independent predictive factors of mortality were: aortic insufficiency (30%, p <0.004), NYHA class IV (20.5%, p < 0.001), left and right heart failure (11.5% and 19.4%, p <0.02), chronic renal insufficiency (18.5%, p <0.04), emergency (37.5%, p <0.001, OR = 4.7), left ventricular ejection fraction (21.1%, p <0.004, OR = 0.9), and redo surgery (35.3%, p <0.001, OR = 6). Mortality was also increased in case of associated coronary revascularization (11.6%), mitral or tricuspid surgery (20%) and ascending aorta procedure (25%). CONCLUSION: Patient functional improvement achieved after valve replacement at the cost of a rather low operative mortality justifies considering octogenarians for surgery. However, decisions should be taken on an individual basis. An earlier referral to surgery before the onset of altered cardiac function could lead to further reductions in hospital mortality.