Elevated Circulating Stem Cells Level is Observed One Month After Implantation of Carmat Bioprosthetic Total Artificial Heart.

The Aeson® total artificial heart (A-TAH) has been developed as a total heart replacement for patients at risk of death from biventricular failure. We previously described endothelialization of the hybrid membrane inside A-TAH probably at the origin of acquired hemocompatibility. We aimed to quantify vasculogenic stem cells in peripheral blood of patients with long-term A-TAH implantation. Four male adult patients were included in this study. Peripheral blood mononuclear cells were collected before A-TAH implantation (T0) and after implantation at one month (T1), between two and five months (T2), and then between six and twelve months (T3). Supervised analysis of flow cytometry data confirmed the presence of the previously identified Lin-CD133+CD45- and Lin-CD34+ with different CD45 level intensities. Lin-CD133+CD45-, Lin-CD34+CD45- and Lin-CD34+CD45+ were not modulated after A-TAH implantation. However, we demonstrated a significant mobilization of Lin-CD34+CD45dim (p = 0.01) one month after A-TAH implantation regardless of the expression of CD133 or c-Kit. We then visualized data for the resulting clusters on a uniform manifold approximation and projection (UMAP) plot showing all single cells of the live Lin- and CD34+ events selected from down sampled files concatenated at T0 and T1. The three clusters upregulated at T1 are CD45dim clusters, confirming our results. In conclusion, using a flow cytometry approach, we demonstrated in A-TAH-transplanted patients a significant mobilization of Lin-CD34+CD45dim in peripheral blood one month after A-TAH implantation. Using a flow cytometry approach, we demonstrated in A-TAH transplanted patients a significant mobilization of Lin-CD34+CD45dim in peripheral blood one month after A-TAH implantation. This cell population could be at the origin of newly formed endothelial cells on top of hybrid membrane in Carmat bioprosthetic total artificial heart.

Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease.

OBJECTIVE: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VICp) mesenchymal-like phenotype was confirmed by CD90+/CD73+/CD44+ expression and multipotent-like differentiation ability. When VICp were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VICp and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VICp-conditioned media and confirmed at the mRNA level in VICp compared with control VIC. Conditioned media from VICp induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VICp involvement in angiogenesis by a VEGF-A dependent mechanism. CONCLUSIONS: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VICp in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.

Possible Link Between the ABO Blood Group of Bioprosthesis Recipients and Specific Types of Structural Degeneration.

Background Pigs/bovines share common antigens with humans: α-Gal, present in all pigs/bovines close to the human B-antigen; and AH-histo-blood-group antigen, identical to human AH-antigen and present only in some animals. We investigate the possible impact of patients' ABO blood group on bioprosthesis structural valve degeneration (SVD) through calcification/pannus/tears/perforations for patients ≤60 years at implantation. Methods and Results This was a single-center study (Paris, France) that included all degenerative bioprostheses explanted between 1985 and 1998, mostly porcine bioprostheses (Carpentier-Edwards second/third porcine bioprostheses) and some bovine bioprostheses. For the period 1998 to 2014, only porcine bioprostheses with longevity ≥13 years were included (total follow-up ≥29 years). Except for blood groups, important predictive factors for SVD were prospectively collected (age at implantation/longevity/number/site/sex/SVD types) and analyzed using logistic regression. All variables were available for 500 explanted porcine bioprostheses. By multivariate analyses, the A group was associated with an increased risk of: tears (odds ratio[OR], 1.61; P=0.026); pannus (OR, 1.5; P=0.054), pannus with tears (OR, 1.73; P=0.037), and tendency for lower risk of: calcifications (OR, 0.63; P=0.087) or isolated calcification (OR, 0.67; P=0.17). A-antigen was associated with lower risk of perforations (OR 0.56; P=0.087). B-group patients had an increased risk of: perforations (OR, 1.73; P=0.043); having a pannus that was calcified (OR, 3.0, P=0.025). B-antigen was associated with a propensity for calcifications in general (OR, 1.34; P=0.25). Conclusions Patient's ABO blood group is associated with specific SVD types. We hypothesize that carbohydrate antigens, which may or may not be common to patient and animal bioprosthetic tissue, will determine a patient's specific immunoreactivity with respect to xenograft tissue and thus bioprosthesis outcome in terms of SVD.

The Cape Town Declaration on Access to Cardiac Surgery in the Developing World.

Mission: to urge all relevant entities within the international cardiac surgery, industry and government sectors to commit to develop and implement an effective strategy to address the scourge of rheumatic heart disease in the developing world through increased access to life-saving cardiac surgery.

Feasibility of Bioengineered Tracheal and Bronchial Reconstruction Using Stented Aortic Matrices.

Importance: Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial. Objective: To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices. Design, Setting, and Participants: Uncontrolled single-center cohort study including 20 patients with end-stage tracheal lesions or with proximal lung tumors requiring a pneumonectomy. The study was conducted in Paris, France, from October 2009 through February 2017; final follow-up for all patients occurred on November 2, 2017. Exposures: Radical resection of the lesions was performed using standard surgical techniques. After resection, airway reconstruction was performed using a human cryopreserved (-80°C) aortic allograft, which was not matched by the ABO and leukocyte antigen systems. To prevent airway collapse, a custom-made stent was inserted into the allograft. In patients with proximal lung tumors, the lung-sparing intervention of bronchial transplantation was used. Main Outcomes and Measures: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. Results: Twenty patients were included in the study (mean age, 54.9 years; age range, 24-79 years; 13 men [65%]). Thirteen patients underwent tracheal (n = 5), bronchial (n = 7), or carinal (n = 1) transplantation. Airway transplantation was not performed in 7 patients for the following reasons: medical contraindication (n = 1), unavoidable pneumonectomy (n = 1), exploratory thoracotomy only (n = 2), and a lobectomy or bilobectomy was possible (n = 3). Among the 20 patients initially included, the overall 90-day mortality rate was 5% (1 patient underwent a carinal transplantation and died). No mortality at 90 days was observed among patients who underwent tracheal or bronchial reconstruction. Among the 13 patients who underwent airway transplantation, major 90-day morbidity events occurred in 4 (30.8%) and included laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. There was no adverse event directly related to the surgical technique. Stent removal was performed at a postoperative mean of 18.2 months. At a median follow-up of 3 years 11 months, 10 of the 13 patients (76.9%) were alive. Of these 10 patients, 8 (80%) breathed normally through newly formed airways after stent removal. Regeneration of epithelium and de novo generation of cartilage were observed within aortic matrices from recipient cells. Conclusions and Relevance: In this uncontrolled study, airway bioengineering using stented aortic matrices demonstrated feasibility for complex tracheal and bronchial reconstruction. Further research is needed to assess efficacy and safety. Trial Registration: clinicaltrials.gov Identifier: NCT01331863.

Multiple reoperations on the aortic valve: outcomes and implications for future potential valve-in-valve strategy.

OBJECTIVES: Surgical mortality and long-term outcomes are important considerations when determining strategies for multiple reoperations on the aortic valve (AV). With the rise of percutaneous valve-in-valve, we sought to evaluate the current outcomes of conventional surgery for AV reoperation, focusing first on the effect of the number of previous AV interventions with a subsequent analysis of the risk factors for adverse outcomes. METHODS: From January 2007 to December 2016, 316 consecutive patients underwent an open redo operation (replacement) on their AV at a single centre. It was the first AV reintervention in 263 patients (Group 1), second in 42 patients (Group 2) and third or more in 11 patients (Group 3). RESULTS: There were 230 men and 86 women, with a median age of 58 (Q1-Q3: 46-70) years. Structural valve deterioration (SVD) of the bioprosthesis (n = 136, 44%), endocarditis (n = 57, 18%) and prosthetic valve dehiscence (n = 41, 13%) were the most common reasons for reintervention. Overall, in-hospital mortality was 7.3%: 7.2% in Group 1, 4.76% in Group 2 and 18.2% in Group 3 (P = 0.233) and ranged from 3.7% for SVD to 14.0% when endocarditis was the reason for reintervention. Higher preoperative New York Heart Association (NYHA) class (III/IV) [odds ratio (OR) 15.9, P = 0.011], injury during re-entry (OR 16.9, P = 0.015), endocarditis (OR 3.7, P = 0.038) and concomitant mitral valve replacement (OR 5.6, P = 0.006) were independent risk factors for in-hospital mortality. Survival at 8 years was 79.0 ± 3.0% for the entire cohort and 88.4 ± 3.2% for re-replacement after SVD. CONCLUSIONS: Multiple AV reoperations carry an acceptable risk of early postoperative mortality, particularly for isolated valve replacements of SVD.

The heart regulates the endocrine response to heart failure: cardiac contribution to circulating neprilysin.

Aims: Heart failure (HF) is accompanied by major neuroendocrine changes including the activation of the natriuretic peptide (NP) pathway. Using the unique model of patients undergoing implantation of the CARMAT total artificial heart and investigating regional differences in soluble neprilysin (sNEP) in patients with reduced or preserved systolic function, we studied the regulation of the NP pathway in HF. Methods and results: Venous blood samples from two patients undergoing replacement of the failing ventricles with a total artificial heart were collected before implantation and weekly thereafter until post-operative week 6. The ventricular removal was associated with an immediate drop in circulating NPs, a nearly total disappearance of circulating glycosylated proBNP and furin activity and a marked decrease in sNEP. From post-operative week 1 onwards, NP concentrations remained overall unchanged. In contrast, partial recoveries in glycosylated proBNP, furin activity, and sNEP were observed. Furthermore, while in patients with preserved systolic function (n = 6), sNEP concentrations in the coronary sinus and systemic vessels were similar (all P > 0.05), in patients with reduced left-ventricular systolic function, sNEP concentration, and activity were ∼three-fold higher in coronary sinus compared to systemic vessels (n = 21, all P < 0.0001), while the trans-pulmonary gradient was neutral (n = 5, P = 1.0). Conclusion: The heart plays a pivotal role as a regulator of the endocrine response in systolic dysfunction, not only by directly releasing NPs but also by contributing to circulating sNEP, which in turn determines the bioavailability of other numerous vasoactive peptides.

Effect of Losartan on Mitral Valve Changes After Myocardial Infarction.

BACKGROUND: After myocardial infarction (MI), mitral valve (MV) tethering stimulates adaptive leaflet growth, but counterproductive leaflet thickening and fibrosis augment mitral regurgitation (MR), doubling heart failure and mortality. MV fibrosis post-MI is associated with excessive endothelial-to-mesenchymal transition (EMT), driven by transforming growth factor (TGF)-ß overexpression. In vitro, losartan-mediated TGF-ß inhibition reduces EMT of MV endothelial cells. OBJECTIVES: This study tested the hypothesis that profibrotic MV changes post-MI are therapeutically accessible, specifically by losartan-mediated TGF-ß inhibition. METHODS: The study assessed 17 sheep, including 6 sham-operated control animals and 11 with apical MI and papillary muscle retraction short of producing MR; 6 of the 11 were treated with daily losartan, and 5 were untreated, with flexible epicardial mesh comparably limiting left ventricular (LV) remodeling. LV volumes, tethering, and MV area were quantified by using three-dimensional echocardiography at baseline and at 60 ± 6 days, and excised leaflets were analyzed by histopathology and flow cytometry. RESULTS: Post-MI LV dilation and tethering were comparable in the losartan-treated and untreated LV constraint sheep. Telemetered sensors (n = 6) showed no significant losartan-induced changes in arterial pressure. Losartan strongly reduced leaflet thickness (0.9 ± 0.2 mm vs. 1.6 ± 0.2 mm; p < 0.05; 0.4 ± 0.1 mm sham animals), TGF-ß, and downstream phosphorylated extracellular-signal-regulated kinase and EMT (27.2 ± 12.0% vs. 51.6 ± 11.7% α-smooth muscle actin-positive endothelial cells, p < 0.05; 7.2 ± 3.5% sham animals), cellular proliferation, collagen deposition, endothelial cell activation (vascular cell adhesion molecule-1 expression), neovascularization, and cells positive for cluster of differentiation (CD) 45, a hematopoietic marker associated with post-MI valve fibrosis. Leaflet area increased comparably (17%) in constrained and losartan-treated sheep. CONCLUSIONS: Profibrotic changes of tethered MV leaflets post-MI can be modulated by losartan without eliminating adaptive growth. Understanding the cellular and molecular mechanisms could provide new opportunities to reduce ischemic MR.

The Carmat Bioprosthetic Total Artificial Heart Is Associated With Early Hemostatic Recovery and no Acquired von Willebrand Syndrome in Calves.

OBJECTIVES: To determine hemostasis perturbations, including von Willebrand factor (VWF) multimers, after implantation of a new bioprosthetic and pulsatile total artificial heart (TAH). DESIGN: Preclinical study SETTING: Single-center biosurgical research laboratory. PARTICIPANTS: Female Charolais calves, 2-to-6 months old, weighing 102-to-122 kg. INTERVENTIONS: Surgical implantation of TAH through a mid-sternotomy approach. MEASUREMENTS AND MAIN RESULTS: Four of 12 calves had a support duration of several days (4, 4, 8, and 10 days), allowing for the exploration of early steps of hemostasis parameters, including prothrombin time; coagulation factor levels (II, V, VII+X, and fibrinogen); and platelet count. Multimeric analysis of VWF was performed to detect a potential loss of high-molecular weight (HMW) multimers, as previously described for continuous flow rotary blood pumps. Despite the absence of anticoagulant treatment administered in the postoperative phase, no signs of coagulation activation were detected. Indeed, after an immediate postsurgery decrease of prothrombin time, platelet count, and coagulation factor levels, most parameters returned to baseline values. HMW multimers of VWF remained stable either after initiation or during days of support. CONCLUSIONS: Coagulation parameters and platelet count recovery in the postoperative phase of the Carmat TAH (Camat SA, Velizy Villacoublay Cedex, France) implantation in calves, in the absence of anticoagulant treatment and associated with the absence of decrease in HMW multimers of VWF, is in line with early hemocompatibility that is currently being validated in human clinical studies.

Starr-Edwards aortic valve: 50+ years and still going strong: a case report.

The advent of the Starr-Edwards mechanical valve marked the beginning of the modern era for heart valve replacement. Nowadays, this valve has been supplanted by lower profile bileaflet mechanical prostheses that are considered to have better haemodynamics, lesser risk of thrombo-embolic complications, and longer durability without structural prosthesis failure. These assumptions often lead physicians to face with the question of systematically replacing functional Starr-Edwards valves in patients undergoing redo operations on other valves. We report the case of a 67-year-old patient who recently underwent mitral valve replacement for symptomatic rheumatic valve disease with an excellent outcome. During the operation, the Starr-Edwards valve in the aortic position implanted 51 years earlier was found to still functioning normally hence was left in place, thereby breaking a new longevity record for a valve prosthesis.

Vien Tim Institut du Coeur: Success of a Congenital Heart Disease Center in a Developing Country.

OBJECTIVE: The goal of the Vien Tim Institute du Coeur is to provide high quality cardiac surgical care to the Vietnamese population with 25% of care allocated to the indigent. This article discusses the history; functional and financial implementation of creating a long-term fully sustainable adult and pediatric cardiac surgery center in Southeast Asia in a developing country. METHODS: The Institut du Coeur in Ho Chi Minh City, Vietnam is a fully functional and financially solvent cardiac surgery center that was formed 28 years ago. It was borne from the Alain Carpentier Foundation which oversees its activity and the Centre Médical International which is an outpatient clinic in Ho Chi Minh City and continues to financially support and oversee the development and future of the Institute. This article details many of the key components to the development of this sustainable program and its evolution. RESULTS: Since 1996, over 25,000 patients with complicated adult and congenital cardiac disease have been treated at the infirmary with support from the Alain Carpentier Foundation since it was established in 1992. The hospital has also performed surgery and treatment to poor patients across Vietnam with over 6,700 impoverished patients having had free operations with an estimated cost of VND230 billion (US$10.2 million). In addition, 96 surgeons and nearly 500 medical staff have carried out charitable health checks on 12,000 patients in many provinces and cities throughout Vietnam. Through profit sharing with the Centre Médical International and corporate and personal donations, proceeds are given to the Institute to help perform roughly 25% of all cardiac surgery free of charge to indigent patients in need of congenital heart surgery. CONCLUSION: The Vien Tim Institute du Coeur has stayed true to its goal of offering high quality cardiac surgical care including congenital heart surgery to a large patient population with one quarter directed to the medically indigent. It also continues to empower and train the health care professionals locally and throughout the country. Creation and growth through this model may help provide a fully functional and financially self-sustaining institution in a developing nation.

Protein metabolism and physical training: any need for amino acid supplementation?

Muscle mass is the major deposit of protein molecules with dynamic turnover between net protein synthesis and degradation. In human subjects, invasive and non-invasive techniques have been applied to determine their skeletal muscle catabolism of amino acids at rest, during and after different forms of physical exercise and training. The aim of this review is to analyse the turnover flux and the relative oxidation rate of different types of muscle proteins after one bout of exercise as well as after resistance and endurance condition of training. Protein feeding in athletes appears to be a crucial nutrition necessity to promote the maintenance of muscle mass and its adaptation to the need imposed by the imposed technical requirements. In resting human individuals, there commended protein daily allowance is about 0.8 g (dry weight) kg−body weight per 24 h knowing that humans are unable to accumulate protein stores in muscle tissues. Nevertheless, practical feeding recommendations related to regular exercise practice are proposed to athletes by different bodies in order to foster their skills and performance. This review will examine the results obtained under endurance and resistance type of exercise while consuming single or repeated doses of various ingestions of protein products (full meat, essential amino acids, specific amino acids and derivatives, vegetarian food). From the scientific literature, it appears that healthy athletes(and heavy workers) should have a common diet of 1.25 g kg−24 h to compensate the exercise training muscle protein degradation and their resyn thesis within the following hours. A nitrogen-balance assay would berecommended to avoid any excessive intake of protein. Eventually, a daily equilibrated food intake would beof primer importance versus inadequate absorption of some specific by-products.

Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve.

BACKGROUND: In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that experimental tethering alone increases mitral valve area in association with endothelial-to-mesenchymal transition. OBJECTIVES: The aim of this study was to explore the clinically relevant situation of tethering and MI, testing the hypothesis that ischemic milieu modifies mitral valve adaptation. METHODS: Twenty-three adult sheep were examined. Under cardiopulmonary bypass, the papillary muscle tips in 6 sheep were retracted apically to replicate tethering, short of producing MR (tethered alone). Papillary muscle retraction was combined with apical MI created by coronary ligation in another 6 sheep (tethered plus MI), and left ventricular remodeling was limited by external constraint in 5 additional sheep (left ventricular constraint). Six sham-operated sheep were control subjects. Diastolic mitral valve surface area was quantified by 3-dimensional echocardiography at baseline and after 58 ± 5 days, followed by histopathology and flow cytometry of excised leaflets. RESULTS: Tethered plus MI leaflets were markedly thicker than tethered-alone valves and sham control subjects. Leaflet area also increased significantly. Endothelial-to-mesenchymal transition, detected as α-smooth muscle actin-positive endothelial cells, significantly exceeded that in tethered-alone and control valves. Transforming growth factor-ß, matrix metalloproteinase expression, and cellular proliferation were markedly increased. Uniquely, tethering plus MI showed endothelial activation with vascular adhesion molecule expression, neovascularization, and cells positive for CD45, considered a hematopoietic cell marker. Tethered plus MI findings were comparable with external ventricular constraint. CONCLUSIONS: MI altered leaflet adaptation, including a profibrotic increase in valvular cell activation, CD45-positive cells, and matrix turnover. Understanding cellular and molecular mechanisms underlying leaflet adaptation and fibrosis could yield new therapeutic opportunities for reducing ischemic MR.

Comparative Histopathological Analysis of Mitral Valves in Barlow Disease and Fibroelastic Deficiency.

Whether Barlow disease (BD) and fibroelastic deficiency (FED), the main causes of mitral valve prolapse (MVP), should be considered 2 distinct diseases remains unknown. Mitral valves from patients who required surgery for severe mitral regurgitation due to degenerative nonsyndromic MVP were analyzed. Intraoperative diagnosis of BD or FED was based on leaflet redundancy and thickness, number of segments involved, and annular dimension. The removed medial scallop of the posterior leaflet and attached chordae were used for histopathological and immunohistological assessment. Histologically, compared to normal controls (n = 3), BD (n = 14), and FED (n = 9) leaflets demonstrated an altered architecture and increased thickness. Leaflet thickness was greater and chordae thickness lower in BD than FED (P < 0.0001). In BD, increased thickness was owing to spongiosa expansion (proteoglycan accumulation) and intimal thickening on fibrosa and atrialis; in FED, local thickening was predominant on the fibrosa side, with accumulation of proteoglycan-like material around the chordae. Collagen accumulation was observed in FED leaflets and chords and decreased in BD. Fragmented elastin fibers were present in BD and FED; elastin decreased in BD but increased in FED leaflets and around chordae. Activated myofibroblasts accumulate in both diseased leaflets and chords, but more abundantly in FED chordae (P < 0.0001), independently of age, suggesting a role of these cells in chordal rupture. There were more CD34-positive cells in BD leaflets and in FED chordae (P < 0.01). In BD leaflets (but not chordae) proliferative Ki67-positive cells were more abundant (P < 0.01) and matrix metalloproteinase 2 levels were increased (P < 0.01) indicating tissue remodeling. Upregulation of transforming growth factor beta and pERK signaling pathways was evident in both diseases but more prominent in FED leaflets (continued on next page)(P < 0.001), with pERK upregulation in FED chordae (P < 0.0001). Most cellular and signaling markers were negligible in control valves. Quantitative immunohistopathological analyses demonstrated distinct changes between BD and FED valves: predominant matrix degradation in BD and increased profibrotic signaling pathways in FED, indicating that BD and FED are 2 different entities. These results may pave the way for genetic studies of MVP and development of preventive drug therapies.

Conduction disorders after tricuspid annuloplasty with mitral valve surgery: Implications for earlier tricuspid intervention.

OBJECTIVE: Tricuspid valve repair has been recently advocated in patients undergoing mitral valve surgery who have mild to moderate secondary tricuspid regurgitation. However, the incidence of heart conduction disorders after combined mitral valve and tricuspid valve interventions has not been evaluated. We sought to analyze the incidence of permanent pacemaker implantations and heart conduction disorders in patients undergoing mitral valve surgery with and without tricuspid valve annuloplasty. METHODS: In 2011 and 2012, among 201 consecutive patients referred to the Hôpital Européen Georges Pompidou for isolated nonischemic mitral valve disease, 113 underwent an isolated mitral valve procedure (group 1) and 88 had a concomitant tricuspid valve ring annuloplasty (group 2). RESULTS: Patients' mean age was 59.7 ± 16.5 years in group 1 and 60.7 ± 14.9 years in group 2 (P = .5). Mean crossclamp time and bypass time were 78 ± 35 minutes and 105 ± 47 minutes in group 1 and 92 ± 36 minutes and 128 ± 50 minutes in group 2, respectively (P = .001 and .005, respectively). Operative mortality was 3% (2.7% in group 1 and 3.2% in group 2, P = .4). Incidence of high-grade heart conduction disorders lasting more than 3 days postoperatively was 14.5% in group 1 and 41.2% in group 2 (P = .001). At 3 years, freedom from permanent pacemaker implantation was 99% ± 2% in group 1 and 94.1% ± 5% in group 2 (P = .02). For the entire cohort, longer crossclamp time (P = .02) and tricuspid ring annuloplasty (hazard ratio, 3.8; P = .001) were independent predictors of heart conduction disorders. CONCLUSIONS: The need for permanent pacemaker implantation is increased after concomitant tricuspid ring annuloplasty in the setting of mitral valve surgery. A clinical period of observation up to 14 days after postoperative heart conduction disorders should be observed before recommending permanent pacemaker placement.

First clinical use of a bioprosthetic total artificial heart: report of two cases.

BACKGROUND: The development of artificial hearts in patients with end-stage heart disease have been confronted with the major issues of thromboembolism or haemorrhage. Since valvular bioprostheses are associated with a low incidence of these complications, we decided to use bioprosthetic materials in the construction of a novel artificial heart (C-TAH). We report here the device characteristics and its first clinical applications in two patients with end-stage dilated cardiomyopathy. The aim of the study was to evaluate safety and feasibility of the CARMAT TAH for patients at imminent risk of death from biventricular heart failure and not eligible for transplant. METHODS: The C-TAH is an implantable electro-hydraulically actuated pulsatile biventricular pump. All components, batteries excepted, are embodied in a single device positioned in the pericardial sac after excision of the native ventricles. We selected patients admitted to hospital who were at imminent risk of death, having irreversible biventricular failure, and not eligible for heart transplantation, from three cardiac surgery centres in France. FINDINGS: The C-TAH was implanted in two male patients. Patient 1, aged 76 years, had the C-TAH implantation on Dec 18, 2013; patient 2, aged 68 years, had the implantation on Aug 5, 2014. The cardiopulmonary bypass times for C-TAH implantation were 170 min for patient 1 and 157 min for patient 2. Both patients were extubated within the first 12 postoperative hours and had a rapid recovery of their respiratory and circulatory functions as well as a normal mental status. Patient 1 presented with a tamponade on day 23 requiring re-intervention. Postoperative bleeding disorders prompted anticoagulant discontinuation. The C-TAH functioned well with a cardiac output of 4·8-5·8 L/min. On day 74, the patient died due to a device failure. Autopsy did not detect any relevant thrombus formation within the bioprosthesis nor the different organs, despite a 50-day anticoagulant-free period. Patient 2 experienced a transient period of renal failure and a pericardial effusion requiring drainage, but otherwise uneventful postoperative course. He was discharged from the hospital on day 150 after surgery with a wearable system without technical assistance. After 4 months at home, the patient suffered low cardiac output. A change of C-TAH was attempted but the patient died of multiorgan failure. INTERPRETATION: This preliminary experience could represent an important contribution to the development of total artificial hearts using bioprosthetic materials. FUNDING: CARMAT SA.