Search

Background— Undersized ring annuloplasty for ischemic mitral regurgitation (MR) is associated with variable results and >30% MR recurrence. We tested whether subvalvular repair by severing second-order mitral chordae can improve annuloplasty by reducing papillary muscle tethering. Methods and Results— Posterolateral myocardial infarction known to produce chronic remodeling and MR was created in 28 sheep. At 3 months, sheep were randomized to sham surgery versus isolated undersized annuloplasty versus isolated bileaflet chordal cutting versus the combined therapy (n=7 each). At baseline, chronic myocardial infarction (3 months), and euthanasia (6.6 months), we measured left ventricular (LV) volumes and ejection fraction, wall motion score index, MR regurgitation fraction and vena contracta, mitral annulus area, and posterior leaflet restriction angle (posterior leaflet to mitral annulus area) by 2-dimensional and 3-dimensional echocardiography. All groups were comparable at baseline and chronic myocardial infarction, with mild to moderate MR (MR vena contracta, 4.6±0.1 mm; MR regurgitation fraction, 24.2±2.9%) and mitral annulus dilatation ( P P P r 2 =0.82, P Conclusions— Comprehensive annular and subvalvular repair improves long-term reduction of both chronic ischemic MR and LV remodeling without decreasing global or segmental LV function at follow-up.

Objectif Plusieurs etudes ont demontre que les patients atteints d’une maladie inflammatoire chronique intestinale (MICI) ont un risque de maladie thromboembolique veineuse (MTEV) multiplie de 1,5 a 3,5. En revanche l’association entre les MICI et les evenements arteriels reste un sujet de debat. Notre etude portait sur l’analyse d’une serie de 6 patients porteurs de MICI et ayant developpe des complications arterielles graves. Methodes Nous avons analyse les dossiers de patients hospitalises dans un service de medecine vasculaire a Paris (groupe hospitalier Paris Saint-Joseph ou HEGP), porteurs d’une MICI, et ayant developpe un evenement thromboembolique arteriel grave. Notre population etait composee de 2 hommes atteints d’une recto-colite hemorragique et de 4 femmes atteintes de maladie de Crohn. Trois patients etaient âges de moins de 50 ans. La moitie des patients avaient un seul facteur de risque cardiovasculaire. Nous avons ensuite realise une revue de la litterature des evenements arteriels decrits dans les populations atteintes de MICI. Resultats Dans notre serie, 5 patients (83 %) avaient une MICI consideree comme active. Les manifestations arterielles pouvaient etre des ischemies aigues (50 %, n = 3) ou des ischemies chroniques (50 %, n = 3) de membres. L’evolution etait marquee par une amputation sous-gonale chez deux de ces patients (33 %, n = 2). Les sites arteriels concernes etaient les arteres des membres inferieurs (50 %, n = 3), l’aorte (33 %, n = 2), l’artere humerale (17 %, n = 1), d’infarctus splenique (17 %, n = 1), de la carotide interne (17 %, n = 1) et des coronaires (17 %, n = 1). Plusieurs descriptions de cas similaires sont retrouvees dans la litterature. Les hypotheses physiopathologiques sont probablement poly-factorielles, expliquees par l’inflammation chronique, l’augmentation de l’epaisseur intima-media, des anomalies biologiques des plaquettes, un etat d’hypercoagulabilite et enfin la corticotherapie au long cours. Conclusion L’imputabilite des MICI dans la survenue d’evenement arteriel ne peut etre formellement demontree mais nous semble majeure. Le controle strict des facteurs de risque cardiovasculaires chez ces patients nous parait indispensable.

Introduction La maladie de Horton, la maladie de Takayasu et la maladie de Behcet sont des vascularites des gros vaisseaux. La corticotherapie constitue la pierre angulaire du traitement. Cependant, un pourcentage eleve de patients developpe des effets secondaires, devient corticodependant ou refractaire a la corticotherapie et/ou aux immunosuppresseurs (methotrexate, cyclophosphamide, azathioprine, mycophenolate mophetil). Depuis quelques annees, l’usage des biotherapies (anti-TNF et anti-interleukine 6 : Tocilizumab) a modifie la prise en charge des vascularites des gros vaisseaux. Objectif Evaluer l’efficacite et la tolerance des biotherapies dans la maladie de Horton, la maladie de Takayasu et l’angio-Behcet. Materiel et methodes Revue de la litterature incluant 43 articles originaux (francais et anglais). Nous avons analyse 156 patients atteints d’une maladie de Takayasu, 59 d’une maladie de Horton et 12 d’un angio-Behcet traites par biotherapies. Resultats Cent trente et un patients atteints d’une maladie de Takayasu ont ete traites par anti-TNF, dont 118 (76 %) ont ete ameliores. La posologie mediane de corticoides avant et apres traitement etait de 17 mg/jour (6,5–30) et 6,5 mg/jour (0–10) respectivement. Trente rechutes sous traitement et trois rechutes a l’arret ont ete rapportees. Vingt-cinq patients atteints d’une maladie de Takayasu ont ete traites par Tocilizumab dont 21 (84 %) ont ete ameliores. La posologie mediane de corticoides avant et apres traitement etait de 21 mg/jour (5–37,5) et 5 mg/jour (0–30) respectivement. Deux rechutes sous traitement ont ete rapportees. Cinquante-neuf patients atteints d’une maladie de Horton ont ete traites par Tocilizumab dont 54 (91,5 %) ont ete ameliores. La posologie mediane de corticoides avant et apres traitement etait de 20 mg/jour (10–60) et 3 mg/jour (0–20) respectivement. Une rechute a l’arret du traitement a ete rapportee. Douze patients atteints d’un angio-Behcet ont ete traites par anti-TNF, tous ont ete ameliores sans rechute rapportee. Au total, 64 effets secondaires ont ete rapportes (en majorite : reactions d’hypersensibilite, infections, cytopenies, hepatites) dont 19 effets secondaires graves et 3 deces. Conclusion Les biotherapies semblent etre tres prometteuses dans le traitement des maladies vasculaires inflammatoires. Cette place devra etre precisee par des etudes controlees.

Purpose: In MRI, thoracic aorta pulse wave velocity (TAPWV) is usually estimated by 2D phase contrast (PC) with either in plane or through plane velocity acquisition. Thanks to technological improvement, 4D PC with full coverage of the TA and 3 dimension velocity encoding thought time can be now achievable in 10min. Our aim was to compare estimation of TAPWV using 4DPC or 2DPC on healthy volunteer. Methods: Acquisitions were performed on a 3 Tesla scanner (GEHC, 750w). 2DPC was done with through plane velocity encoding on an axial oblique slice perpendicular to ascending and descending TA. 4D acquisition covered the full TA volume from the aortic valve to diaphragm. Segmentation and velocity estimates were done by using cloud computing (Arterys). Optimal data view sharing was applied to obtain 8ms and 16ms temporal resolution for 2DPC and 4DPC, respectively. Flow data curves where further computed on homemade software (artfun) to assess PWV for both 2D and 4D acquisition. Results: 31 healthy volunteers (13 male, age 50.9y ±18.6) were included. Correlation coefficient between 4DPC and 2DPC PWV was 0.69 (p

Imaging intramyocardial vascular flows in real-time could strongly help to achieve better diagnostic of cardiovascular diseases. To date, no standard imaging modality allows describing accurately myocardial blood flow dynamics with good spatial and temporal resolution. We recently introduced a novel ultrasonic Doppler imaging technique based on compounded plane waves transmissions at ultrafast frame rate. The high sensitivity of this ultrafast Doppler technique permits to image the intramyocardial blood flow and its dynamics. A dedicated demodulation-filtering process is implemented to compensate for the large tissue velocity of the myocardium during the cardiac cycle. A signed power Doppler processing provides the discrimination between arterial and venous flows. Experiments were performed in vivo in a large animal open chest model ( N = 5 sheep) using a conventional ultrasonic probe placed at the surface of the heart. Results show the capability of the technique to image intramyocardial vascular flows in normal physiological conditions with good spatial (200 μm) and temporal resolution (10 ms). Flow dynamics over the cardiac cycle were investigated and the imaging method demonstrated a phase opposition of flow waveforms between arterial and venous flows. Finally, ultrafast Doppler combined with tissue motion compensation was found able to reveal vascular flow disruption in ischemic regions during occlusion of the main diagonal coronary artery.

Background Because measurement of arterial stiffness is highly dependent on blood pressure (BP), methods independent of BP are required. Ultrafast echography (UFE, Supersonic Imagine, Aix-en-Provence, France) makes use of very fast sampling rate (up to 10kHz), so transient events such as pressure wave arrival can be tracked. This method has never been tested against classical echotracking (Artlab, Esaote, Maastricht, NL) and carotid-femoral pulse wave velocity (cf-PWV, Sphygmocor, AtCor, Sydney, Australia). Methods We included 56 subjects, 27 normotensives (NT) and 29 essential hypertensives (HT), matched for age and sex. We optimized UFE algorithms for pressure wave detection and tracking, for both foot of the wave (FW) and dicrotic notch (DN) PWV. Results Feasibility appears good (FW: 78%, DN: 96%). The relations of arterial stiffness with age and blood pressure were stronger for echotracking and cf-PWV than for UFE. DN wave fronts appeared better associated with cf-PWV (r = 0.32, p Conclusions After optimizing algorithms for wave front identification and tracking, UFE appears as a promising technique for assessing arterial stiffness. DN showed the best associations with echotracking, whereas FW did not provide meaningful data. As previously shown by Hermeling et al (J Hypertens 2008 and 2009), FW is not appropriate for local stiffness measurement likely because of very early wave reflections.

We have previously proposed a novel method for measuring arterial stiffness using shear wave imaging (SWI). In this study, we evaluate the performance of this method on a healthy population (N=30) and we compare it to local measurement of the arterial pulse wave velocity (PWV) achieved at the same arterial site using ultrafast imaging. Ultrafast imaging was used to track shear wave induced remotely by acoustic radiation force at the carotid site at a frame rate of 10000 images/second with a 8 MHz ultrasound probe. SWI was acquired with a repetition rate of 7 Hz in order to measure stiffness variation over the cardiac cycle. The axial-velocity field in the imaging plane was obtained using conventional Doppler algorithm. As shown in a previous study, acoustic radiation force applied normally to the arterial wall induces mainly a flexural guided mode (F0) which propagates between 100 to 1500 Hz. The dispersion curve of this mode is extracted from the 2D-FFT of the shear wave spatio-temporal velocity field within and along the arterial wall. The shear modulus is then estimated by a theoretical fit of the experimental dispersion curve. Ultrafast imaging was also used to measure the tissue velocity of the arterial wall at the same site at a frame rate of 1000 images/s during 1 second. PWV was estimated by tracking the pulse wave along the arterial wall based on spatio-temporal velocity field at early and end-systole. Each ultrasound measurement was repeated 3 times on each carotid to estimate the reproducibility of the technique. Lower reproducibility was found on systolic PWV measurements. Thanks to its higher frequency content, the PWV at end-systole was measured more accurately and was found to be more reliable, but was not visible in all volunteers. In contrast, SWI offered high reproducibility. Moreover, arterial stiffness was achieved 6 times per seconds contrary to one time per second for PWV, giving access to the arterial stiffness time variation during the cardiac cycle.

To the Editor: In their recent article in Circulation , De Varennes et al1 proposed to test the efficacy of posterior leaflet extension with remodeling annuloplasty on 44 patients with type IIIb ischemic mitral regurgitation (MR). In their introduction, the authors explain that most often ischemic MR mechanism is complex, “and the resulting MR jet is composed of a central and posteriorly directed jet of regurgitation (Carpentier type I and III).” In the discussion, the authors further explain …

Background To report the rare diagnosis and the surgical treatment of a young patient presenting a symptomatic dissection of the abdominal aorta revealing a Takayasu’s arteritis (TA). Methods and Results A 24-year-old woman developed a painful chronic dissection of the infrarenal aorta associated with a claudication of both lower extremities. As the patient was still symptomatic despite an optimal medical treatment, a surgical revascularization was proposed. An aortobifemoral bypass was performed allowing the removal of infrarenal aorta and the histologic diagnosis of TA. Conclusion Isolated abdominal aortic dissection is an unusual event in TA, and this is the first surgically treated case. Only few reports of aortic dissection in TA have been published so far which are commented in this article.

The concept of shear wave elastography is applied to the heart. The goal of this study is to demonstrate the potential of this technique for quantifying the elasticity time variation of the myocardium. Experiments are performed in vivo on N=10 sheep with a linear high frequency probe placed directly on the myocardium. The feasibility of generating and imaging the propagation of shear wave in the beating heart and estimating locally the myocardium elasticity at each stage of a single heart cycle is investigated by repeating acquisition of shear wave propagation between 10 and 20 times per second. The dependence of estimated shear modulus with probe angle (short axis to long axis), depth and left ventricle pressure is studied in vivo and ex vivo. The short term effect of a local ischemia is also studied by coronary arteries ligature, showing the sensitivity of the technique to a local loss of contractility in the myocardium. Finally, this study shows the potential of shear wave elastography as a quantification tool of myocardium mechanical properties.

The concept of synthetic imaging using circular wave is proposed to image with a very large field of view and at a very high frame rate (≫1000 images/sec) heart motions with a conventional cardiac phased array probe. The goal of this study is to demonstrate in vivo the feasibility of this technique. Experiments are first performed in-vitro on ultrasound phantoms to optimize the trade-off between image quality and frame rate. An in vivo study is then performed on 10 sheep with a conventional phased array probe placed directly on the epicardium at different locations to obtain cine-loop of a complete heart cycle in the conventional imaging planes (long and short axis). After classical post processing of acquired cine-loop (wall tracking and tissue Doppler velocity estimation), the propagation of mechanical waves induced naturally during the heart cycle such as aortic and mitral valves closure can be observed.

The concept of shear wave elasticity imaging is applied to arteries. The goal of this study is to demonstrate the potential of this technique for precisely and non-invasively quantifying the elasticity of the arterial wall. Experiments are performed in arterial phantoms composed of elastic cylindrical shells that have an elastic modulus in the range of human arteries stiffness. The feasibility of imaging the shear wave propagation in real-time and measuring the frequency dispersion over a large bandwidth (100-1500 Hz) is demonstrated with good accuracy. Experimental dispersion curves are in good agreement with the theoretical curves computed for each phantom. Based on the dispersion measurement, a simple method is developed to derive the elastic modulus of the arterial wall. Finally, the feasibility of quantifying non-invasively the elastic modulus of the arterial wall is demonstrated in vivo on healthy volunteers.

Critical limb ischemia is associated with a high risk of amputation and death. Several medical options have been tested on patients who cannot be revascularized surgically, but none has shown any effect on the amputation rate at 6 months.Gene and cell therapy intended to stimulate angiogenesis have been tested in phase I and II clinical trials. These innovative approaches appear both feasible and safe. Large randomized clinical trials are necessary to demonstrate their benefits and long-term safety.

Background. We have previously demonstrated that severing two second-order chordae to the anterior mitral leaflet (AL) in sheep does not adversely affect LV size and function acutely. Objectives. This study tested whether chordal cutting exacerbates long-term LV remodeling when applied to treat ischemic mitral regurgitation (MR) in a chronic myocardial infarction (MI). Methods. A posterolateral MI was created in 18 sheep by ligation of obtuse marginal branches. After chronic remodeling and MR development at 2 months, sheep were randomized to sham surgery versus anterior leaflet (AntL) or bileaflet (BiL) second-order chordal cutting (n=6 each), techniques in clinical application. 2D and 3D echo at baseline, chronic infarction (2 months), and follow-up at a mean of 6.5 months post-MI (sacrifice) measured LV end-diastolic and end-systolic volume (EDV and ESV), ejection fraction (EF), wall motion score index (WMSi), and posterior leaflet (PL) restriction angle relative to the annulus. Results. All measurements were comparable among groups at baseline and chronic MI. At sacrifice, AntL and BiL chordal cutting limited the progressive remodeling seen in controls. LVESV increased by 33.0±7.2% and 28.0±5.0% relative to chronic MI with AntL and BiL chordal cutting, versus 109.0±8.7% in controls (p Conclusions: Cutting secondary chordae in the chronic post-MI setting does not adversely affect long-term LV remodeling, and limits progressive increases in LV volumes.

Human embryonic stem (HES) cells can give rise to cardiomyocytes in vitro. However, whether undifferentiated HES cells also feature a myocardial regenerative capacity after in vivo engraftment has not been established yet. We compared two HES cell lines (HUES-1 and I6) that were specified toward a cardiac lineage by exposure to bone morphogenetic protein-2 (BMP2) and SU5402, a fibroblast growth factor receptor inhibitor. Real-time polymerase chain reaction (PCR) revealed that the cardiogenic inductive factor turned on expression of mesodermal and cardiac genes (Tbx6, Isl1, FoxH1, Nkx2.5, Mef2c, and α-actin). Thirty immunosuppressed rats underwent coronary artery ligation and, 2 weeks later, were randomized and received in-scar injections of either culture medium (controls) or BMP2 (±SU5402)-treated HES cells. After 2 months, human cells were detected by anti-human lamin immunostaining, and their cardiomyocytic differentiation was evidenced by their expression of cardiac markers by reverse transcription-PCR and immunofluorescence using an anti-β myosin antibody. No teratoma was observed in hearts or any other organ of the body. The ability of cardiac-specified HES cells to differentiate along the cardiomyogenic pathway following transplantation into infarcted myocardium raises the hope that these cells might become effective candidates for myocardial regeneration. Disclosure of potential conflicts of interest is found at the end of this article.

Diabetes mellitus is an independent risk factor for peripheral artery disease. Life expectancy is 41 months for diabetic patients with an ischemic ulcer. The characteristics of diabetic arteriopathy make its treatment more difficult than in non-diabetic patients. Few data are available about the surgical treatment of arteriopathy in diabetic patients (including angioplasty or bypass), especially in case of distal arteriopathy. The choice of the procedure depends on multiple factors such as the disease localization, its extent, distal blood flow and vascular disease-related surgical risk. The principal aim of revascularisation is to restore direct flow to the foot in order to ensure wound healing and limb salvage. With percutaneous endoluminal angioplasty, limb salvage can be achieved in more than 80% of patients at 1-3 years. The percutaneous procedure is less invasive than open surgery, there are fewer complications, and morbidity and mortality rates are reduced; moreover, a second procedure remains possible in the future. With bypass surgery, the rate of limb salvage exceeds 80% at five years. Nevertheless, peri-operative mortality reaches 3% and arterial anatomy, patient-related risks factors or venous graft availability may be limitations. New endovascular techniques especially designed for the distal arteries of the lower limbs enable very distal revascularization with morbidity and mortality rates lower than with surgery.

Dans la leucemie myeloide chronique (LMC), malgre un benefice clinique evident du nilotinib, inhibiteur de tyrosine kinase de 2e generation, chez les patients resistants ou intolerants a l’imatinib et chez les patients nouvellement diagnostiques, des donnees recentes suggerent que le nilotinib a une propension a augmenter le risque d’evenements occlusifs arteriels. Methode Ceci survenant en particulier chez les patients presentant des facteurs de risque preexistants cardiovasculaires et etant donne le role cle des lipides dans les maladies cardiovasculaires, nous avons etudie le profil lipidique et le risque cardiovasculaire global avant et pendant le traitement par nilotinib dans une serie de 27 patients consecutifs, suivis au moins 12 mois, dans le cadre d’une etude monocentrique. Resultats Les analyses montrent que dans les 3 premiers mois de traitement par nilotinib, le cholesterol total est passe de 1,8 ± 0,38 g/L a 2,24 ± 0,47 g/L, le low density lipoprotein (LDL)-cholesterol de 1,13 ± 0,30 g/L a 1,46 ± 0,38 g/L et le high density lipoprotein (HDL)-cholesterol de 0,44 ± 0,15 g/L a 0,58 ± 0,18 g/l (p Conclusion Que l’hypercholesterolemie soit le principal moteur des evenements occlusifs arteriels est incertain : un suivi plus long serait necessaire afin de demontrer que l’hypercholesterolemie induite par le nilotinib augmente le risque a long terme de maladies atherosclerotiques. Neanmoins, etant donne les proprietes atherogenes du LDL-cholesterol, nous incitons a detecter les troubles lipidiques avant et pendant la prescription de nilotinib, compte tenu de leur frequence, et d’adapter en consequence les regles hygieno-dietetiques, voire introduire un hypolipemiant en raison du potentiel de complications cardiovasculaires a long terme.

Because measurement of arterial stiffness is highly dependent on blood pressure (BP), methods independent of BP are required. Ultrafast echography (UFE, Supersonic Imagine, Aix en Provence, France) makes use of very fast sampling rate (up to 10 kHz), so transient events such as pressure wave arrival can be tracked. This method has never been tested against classical echotracking (Artlab, Esaote, Maastricht, NL) and carotid-femoral pulse wave velocity (cf-PWV, Sphygmocor, AtCor, Sydney, Australia). We included 56 subjects, 27 normotensives (NT) and 29 essential hypertensives (HT), matched for age and sex. We optimized UFE algorithms for pressure wave detection and tracking, for both foot of the wave (FW) and dicrotic notch (DN) PWV. Feasibility appears good (FW: 78%, DN: 96%). The relations of arterial stiffness with age and blood pressure were stronger for echotracking and cf-PWV than for UFE. DN wave fronts appeared better associated with cf-PWV (r = 0.32, p < 0.001) and carotid PWV (r = 0.47, p < 0.001). FW was not associated with cf-PWV nor with carotid PWV. The residuals between DN and carotid PWV were not associated with BP or age. Similar associations between DN and cf-PWV/carotid PWV were found in NT and HT. Conclusion: After optimizing algorithms for wave front identification and tracking, UFE appears as a promising technique for assessing arterial stiffness. DN showed the best associations with echotracking, whereas FW did not provide meaningful data. As previously shown by Hermeling et al (J Hypertens 2008 and 2009), FW is not appropriate for local stiffness measurement likely because of very early wave reflections.

Background— Severing a limited number of second-order chordae to the anterior leaflet can improve ischemic mitral regurgitation (MR). Some concerns have been raised regarding possible influence on regional and global left ventricle (LV) function. We evaluated changes in cardiac function in 5 normal sheep with cutting of pre-instrumented chords in the beating heart to maintain constant load. Methods and Results— Under cardiopulmonary bypass, wires were placed around the 2 central basal chordae and brought outside the heart, which was restarted. Hemodynamic and imaging data were collected before and after chordal cutting by radiofrequency ablation using those wires. Segmental contractility was assessed invasively using sonomicrometers and noninvasively using Doppler tissue velocity and strain rate (with strain rate viewed as less load-dependent than ejection fraction) at 6 sites: base, mid-ventricle, and apex along the anteroseptal and posterolateral walls. We found no changes from before to after chordal cutting in LV end-diastolic volume (47.2±3.3 after cutting versus 48.4±4.6 mL before cutting, P =0.66), end-systolic volume (21.5±1.2 versus 22.3±2.8 mL, P =0.68), ejection fraction (54.2±1.8 versus 54.2±2.7%, P =0.96), systolic ventricular elastance (7.28±1.68 versus 7.66±2.11 mm Hg/mL, P =0.64), preload-recruitable stroke work (46.6±7.7 versus 50.2±10.7 mm Hg, P =0.76), and LVdP/dt (1480±238 versus 1392±250 mm Hg/s, P =0.45). Doppler tissue velocities and longitudinal strain rates surrounding the papillary muscles were unchanged, as were sonomicrometer longitudinal and mediolateral absolute strains. No wall motion abnormalities were visible around the papillary muscles, and no MR developed. Conclusion— We find no evidence for acutely decreased global or segmental LV contractility with chordal cutting. This absence of adverse effects is consistent with long-term clinical experience with cutting these chords in valve repair.

Background— Skeletal myoblast (SM) transplantation (Tx) in a post-myocardial infarction (MI) scar experimentally improves left ventricular (LV) ejection fraction (EF). Short-term follow-up (FU) studies have suggested that a similar benefit could clinically occur despite an increased risk of LV arrhythmias. Methods and Results— We report the long-term FU of the first worldwide cohort of grafted patients (n =9, 61.8±11.6 years, previous MI, EF ≤35%) operated on (autologous SM Tx and bypass surgery) in 2000 to 2001 and evaluated before Tx, at 1 month (M1) and at a median FU of 52 (18 to 58) months after Tx (37 patient-years). NYHA class improved from 2.5±0.5 to 1.8±0.4 at M1 ( P =0.004 versus baseline) and 1.7±0.5 at FU ( P =not significant versus M1; P =0.0007 versus baseline). EF increased from 24.3±4% to 31±4.1% at M1 (+28%, P =0.001 versus baseline) and remained stable thereafter (28.7±8.1%, +18% versus baseline). There were 5 hospitalizations for heart failure in 3 patients at 28.6±9.9 months, allowing implant in 2 patients with a resynchronization pacemaker. An automatic cardiac defibrillator (ACD) was implanted in 5 patients for nonsustained (n =1) or sustained (n =4) ventricular tachycardia at 12.2±18.6 (1 to 45) months. Despite a beta-blocker/amiodarone combination therapy, there were 14 appropriate shocks for 3 arrhythmic storms in 3 patients at 6, 7, and 18 months after ACD implantation. Conclusions— In this cohort of severe heart failure patients both clinical status and EF stably improve over time with a strikingly low incidence of hospitalizations for heart failure (0.13/patient-years) and the arrhythmic risk can be controlled by medical therapy and/or on-request ACD implantation.

International audience; Objectives: This study was designed to assess whether post-myocardial infarction (MI) in-scar transplantation of skeletal myoblasts (SM) could reduce chronic ischemic mitral regurgitation (MR) by decreasing left ventricular (LV) remodeling.Background: Extensive work has confirmed the relationship between ischemic MR and post-myocardial infarction (MI) remodeling of the LV.Methods: An infero-posterior MI was created in 13 sheep, thereby resulting in increasing MR. Two months post-MI, the animals were randomized and in-scar injected with expanded autologous SM (n = 6, mean: 251 x 10(6) cells) or culture medium only (n = 7). Three-dimensional echocardiography was performed at baseline, before transplantation, and for two months thereafter (sacrifice), with measurements of LV end-diastolic and end-systolic volumes (ESV), ejection fraction (EF), MR stroke volume, and leaflet tethering distance; wall motion score index (WMSi) was assessed by two-dimensional echo.Results: Measurements were similar between groups at baseline and before transplantation. At sacrifice, transplantation was found to have reduced MR progression (regurgitant volume change: -1.83 +/- 0.32 ml vs. 5.9 +/- 0.7 ml in control group, p < 0.0001) and tethering distance (-0.41 +/- 0.09 cm vs. 0.44 +/- 0.12 cm in control group, p < 0.001), with significant improvement of EF (2.01 +/- 0.94% vs. -4.86 +/- 2.23%, p = 0.02), WMSi (-0.25 +/- 0.11 vs. 0.13 +/- 0.03 in controls, p < 0.01) and a trend to a lesser increase in ESV (23.3 +/- 3.5 ml vs. 35.4 +/- 4.2 ml in control group, p = 0.055).Conclusions: Autologous skeletal myoblast transplantation attenuates mild-to-moderate chronic ischemic MR, which otherwise is progressive, by decreasing tethering distance and improving EF and wall motion score, thereby enhancing valve coaptation. These data shed additional light on the mechanism by which skeletal myoblast transplantation may be cardioprotective.

Summary Background Heart failure develops after myocardial infarction and is a major cause of morbidity and mortality. The ability to direct differentiation of embryonic stem cells (ESC) towards a cardiomyogenic phenotype makes them an attractive therapeutic option for cardiac repair, but species-specific and individual-specific immunological imprinting remains a hurdle. Our aim was to ascertain whether the purported immune privilege of ESC allows for their cross-species engraftment in a clinically relevant large-animal model. Methods We studied engraftment and differentiation of cardiac-committed mouse ESC in 18 sheep in which a myocardial infarction had been induced; nine controls received medium and nine sheep (five of which were immunosuppressed) received ESC. The gain in myocardial function was measured by echocardiography 1 month after cell transplantation. Findings Cardiac-committed murine ESC engrafted in infarcted myocardium of immunosuppressed and immunocompetent sheep, and differentiated into mature cardiomyocytes that expressed connexins. Colonisation of the scar area by ESC was accompanied by a functional benefit of the damaged myocardium. Left-ventricular ejection fraction deteriorated in the control group by a median of 9·9% (range −20 to 0·3) relative to baseline (p=0·011) whereas in the treated group it improved by 6·6% (−5·7 to 50·8; comparison between groups p=0·002). Interpretation These findings obtained in a clinically relevant large-animal model of heart failure strengthen the potential therapeutic use of ESC to regenerate the severely dysfunctional myocardium and bring additional evidence for an immune privilege of these cells.

It has been postulated that systemic infection with pathogens such as Porphyromonas gingivalis (Pg) elevates the inflammatory response and increases susceptibility to atherosclerosis. We hypothesized that Doxycycline would be beneficial in diet- and/or Pg-induced atherosclerosis given its role in various cell functions and matrix remodeling.ApoE+/- mice were inoculated weekly with Pg and treated with either Doxycycline or saline; animals were fed either a high-fat or chow diet. Animals were euthanized at 14 or 24 weeks and histomorphometric analysis of atheromatous lesions in proximal aorta, levels of SAA and serum cytokine profiling were performed. Histomorphometric analysis demonstrated that in non-infected mice fed a high fat diet, Doxycycline treatment resulted in a reduction of mean lesions from 10.5%+/-.49 to 1.09%+/-0.102 (p0.05) at 14 weeks and a reduction from 21.5%+/-6.49 to 8.26%+/-0.162 (p=0.106) at 24 weeks. Chow-fed Pg mice treated with Doxyclycline also resulted in a reduction from 0.62%+/-0.128 to 0.0%+/-0.0 (p0.05) at 14 weeks and a reduction from 0.92%+/-0.23 to 0.0%+/-0.0 (p0.05) at 24 weeks. Administration of Doxycycline to mice fed a high fat diet and Pg-inoculated resulted in a reduction of mean percentage of atheromatous lesions from 16.46%+/-1.69 to 1.141%+/-0.23 (p0.05) at 14 weeks and a reduction from 25.27%+/-1.734 to 0.428%+/-0.033 (p0.05) at 24 weeks. At this timepoint, SAA levels in Pg-infected animals were reduced by five-fold and three-fold in Doxycycline-treated chow and high fat-diet groups, respectively. Cytokine antibody arrays revealed a marked reduction in the levels of pro-inflammatory cytokines in Doxycycline-treated groups whether Pg-infected or fed a high fat diet while anti-inflammatory cytokines were not affected. Consistent with the role of Doxycycline on matrix proteases, at 24 weeks MMP-9 Serum levels were markedly reduced by 60% (p0.05) and 30% (p0.05) with Doxycycline treatment in Pg-infected high fat and chow diet groups, respectively.Doxycycline decreases pro-inflammatory cytokines and results in reduction of atherosclerosis in ApoE+/-Pg-inoculated and/or high fat diet fed mice.

Background— Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Leaflet closure is restricted by tethering to displaced papillary muscles, and is, therefore, incompletely treated by annular reduction. In an acute ischemic model, we reduced such MR by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. Whether this is effective without prolapse, recurrent MR, or left ventricular (LV) failure in chronic persistent ischemic MR, despite greater LV remodeling, remains to be established. Therefore, we studied 7 sheep with chronic inferobasal infarcts known to produce progressive MR over 2 months. In all of those sheep, after a mean of 4.1 months, the 2 central basal (intermediate) chordae were cut at the chronic ischemic MR stage. 3-Dimensional echo quantified MR, LV function, and valve geometry. Five other sheep were followed for a mean of 7.8±1.2 months after inferobasal infarction with chordal cutting. Results— All 7 of the sheep with chronic ischemic MR (increased from 1.4±0.4 to 11.1±0.5 mL/beat, regurgitant fraction=39.0±4.2%, P P P =not significant [NS]). The five sheep with long-term follow-up showed no prolapse or MR, and no significant post-infarct decrease in LV ejection fraction (EF; 38.9±2.4% to 41.4±1.2%, P =NS). Conclusion— Cutting a minimum number of basal (intermediate) chordae can improve coaptation and reduce chronic persistent ischemic MR without impairing LVEF. No adverse effects were noted long-term after chordal cutting at the time of infarction.

Effective valve repair in patients with mitral regurgitation (MR) demands an understanding of its mechanism. In patients with ischemic heart disease and functional MR, which doubles late mortality, normal leaflets are apically displaced. This reflects an altered balance of forces acting on the leaflets: increased tethering forces restricting closure, resulting from an altered geometry of leaflet attachments, and decreased ventricular forces acting to close the leaflets. Extensive evidence confirms a central and predominant role of tethering as the final common pathway inducing functional MR; left ventricular (LV) pressure dynamically modulates the orifice area. Because ischemic MR is a disease of the entire mitral complex, including the remodeling LV, reducing annular size alone is often ineffective. Undersizing rings attempts to compensate for tethering; new and potentially more effective strategies directly address tethering by infarct plication, papillary muscle repositioning with a localized patch, or basal chordal cutting to increase coaptational surface area without prolapse. A comprehensive understanding of the valve in its ventricular context, therefore, provides new opportunities for successful valve repair in patients.

Objectif Determiner un score pronostique de risque de morbi-mortalite a un an pour les patients admis a l’hopital pour la prise en charge d’un arteriopathie des membres inferieurs symptomatique. Materiel et methodes Les facteurs associes a la morbi-mortalite a un an ont ete determines grâce au registre multicentrique COPART, incluant des patients consecutifs, hospitalises dans les services de medecine vasculaire des CHU de Toulouse, Bordeaux, Limoges et Paris HEGP. Les patients ont ete suivis prospectivement pendant un an. Un score de risque a ete construit sur une cohorte d’observation (cohorte de Toulouse), puis valide dans une cohorte de validation, independante de la premiere (cohorte de Bordeaux et Limoges). La valeur discriminante du score ainsi que sa transportabilite ont ete etudiees. Resultats Nous avons analyse les donnees de 623 patients arteriopathes pour la cohorte d’observation. Le score de risque comprend les facteurs suivants : âge ≥ 80 ans (+1,5) ; stade de Rutherford 4, 5, 6 (+2) ; antecedent d’insuffisance cardiaque (+2) ; clairance de la creatinine : ≤ 30 mL min −1 1,73 m −2 (+1,5) ; une clairance de la creatinine : 0,30–0,59 mL min −1 1,73 m −2 (+1) ; hyperleucocytose ≥ 10000 (+1) et un traitement par statine a l’admission (−1). Le risque de morbi-mortalite a un an augmente significativement avec le resultat du score : bas risque ( 3,5 points) = 60,5 % de morbi-mortalite. Les resultats de la validation de ce score seront presentes lors du congres. Conclusion Ce score est un outil de stratification du risque a l’admission pour les patients hospitalises pour la prise en charge d’un arteriopathie atheromateuse des membres inferieurs, base sur 6 variables facilement identifiables en pratique clinique. Une fois valide, il pourrait permettre d’optimiser la prise en charge medicale de ces patients.

Background Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Because such MR is related to increased leaflet tethering by displaced attachments to the papillary muscles (PMs), it is incompletely treated by annular reduction. We therefore addressed the hypothesis that such MR can be reduced by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. This was tested in 8 mitral valves: a porcine in vitro pilot with PM displacement and 7 sheep with acute inferobasal infarcts studied in vivo with three-dimensional (3D) echo to quantify MR in relation to 3D valve geometry. Methods and Results In all 8 valves, PM displacement restricted leaflet closure, with anterior leaflet angulation at the basal chord insertion, and mild-to-moderate MR. Cutting the 2 central basal chordae reversed this without prolapse. In vivo, MR increased from 0.8±0.2 to 7.1±0.5 mL/beat after infarction and then decreased to 0.9±0.1 mL/beat with chordal cutting ( P r 2 =0.76). Conclusions Cutting a minimum number of basal chordae can improve coaptation and reduce ischemic MR. Such an approach also suggests the potential for future minimally invasive implementation.

Background Changes in mitral valve (MV) elasticity or distensibility occur in disease and directly affect MV function, contributing to MV prolapse (MVP) or flail vs restricted coaptation of stiffer leaflets in functional mitral regurgitation (FMR) and MV stenosis (MS). Recent studies suggest MV distensibility may be modified to reduce MR, but distensibility has only been measured in excised MVs. Our aim was to test the feasibility of obtaining a noninvasive measure of MV distensibility in patients by measuring systolic change in anterior leaflet length (ALL) or anterior leaflet strain; and to test the hypothesis that these measures vary in diseases with known altered MV elasticity. Methods ALL was quantified in a long-axis view standardized by 3D echo in 80 patients: 20 each with normal hearts, MVP, FMR and MS. Distensibility was measured as end-systolic (ES) – end-diastolic (ED) total ALL normalized to an ED reference; and alternatively as mid-leaflet strain measured by tracking echo features. Results ALL was greater in all disease groups vs normal (p 2-fold higher (17.6 ± 11.2%) in MVP; it was 63-76% lower (2.9 ± 3.0%, 1.9 ± 3.1%) in FMR and MS, with comparable results for segmental AL strain (Table). Conclusion Noninvasive echocardiographic measures of MV distensibility based on systolic changes in total length or segmental strain are feasible. Results are consistent with excised valve biomechanics, showing increased distensibility in MVP and decreased values in FMR and MS. Ultimately, these techniques have the potential to monitor response to new therapies that aim to improve MV biology and mechanics to reduce MR. Parameter unit Norm MVP FMR MS ALL systole mm. 26.6 ± 2.7 39.7 ± 5.6 * 32.7 ± 4.1 * 33.4 ± 5.0 * ALL diastole mm. 24.5 ± 3.1 33.5 ± 3.2 * 32.0 ± 4.2 * 32.8 ± 4.9 * ALL (sys-dia)/dia % 7.9 ± 7.4 17.6 ± 11.2 * 2.9 ± 3.0 * 1.9 ± 3.1 * SegL (ES-ED)/ED % 9.1 ± 4.8 19.6 ± 10.9 * 3.2 ± 2.6 * 2.7 ± 3.7 * * P

Background Nilotinib is approved for use in pts with CML after failure of imatinib and in newly diagnosed CP-CML. However, several studies report a nilotinib-associated risk of AOE, especially in pts with preexisting risk factors for CVD. Since CVD are a major cause of disability and death worldwide and result from complex interactions between multiple risk factors, we aimed at determining whether CVD risk estimation using the 2012 European Society of Cardiology (ESC) classification could be useful to identify patients at high risk of AOE during nilotinib therapy. Methods Pts (n=75) treated with nilotinib upfront or after failure of prior TKI at our institution were included provided that baseline risk factors for CVD and prior history of established CVD could be retrospectively collected. Risk factors included age, tobacco use, diabetes mellitus (DM), arterial hypertension (AH), dyslipidemia and increased body mass index (BMI). Patients were categorized into 2 groups according to ESC 2012 classification: low/moderate (L/M) and high/very high (H/VH) CVD risk. H/VH included pts with any of the following: established CVD, DM, severe AH, familial dysplipidemia or a SCORE (systematic coronary risk evaluation project) ≥5%. Results At nilotinib initiation, median age was 51 years (19-76), 41 pts (54.7%) were males. Nilotinib was given upfront in 28 pts (37%) and after failure of imatinib or dasatinib following imatinib in 47 pts (63%). Median time from diagnosis was 1 month (0.3-4) in the former group and 25 months (2-130) in the latter. Median duration of TKI exposure prior to nilotinib in the latter group was 22 months (0.4-91). Initial nilotinib dosing regimen was 400mg BID in 42 pts (56%) and 300mg BID in 33 pts (44%). Median duration of nilotinib treatment of 28 months (3-76) and median follow-up was 30 months (3-77). At baseline, medical history revealed H/VH risk category in 15 pts (20%) including established CVD in 6 pts (8%) (all diagnosed before CML), DM in 10 pts (13.3%), severe AH in 1 pt (1.3%), familial dyslipidemia in 1 pt (1.3%) and a SCORE ≥5% in 2 pts (2.6%). Median number of CVD risk factors was 1 (0-6) including age ≥ 45 years in men and ≥ 55 years in women in 37 pts (49.3%), active smoking or ceased during the previous year in 12 pts (16.7%), DM in 10 pts (13.3%), AH in 14 pts (18.7%), dyslipidemia in 10 pts (13.3%) and BMI ≥ 25 kg/m2in 20 pts (38.6). Nilotinib was discontinued in 23 pts (30.7%) due to adverse events (10 pts), resistance (7 pts), TKI discontinuation study (4 pts) or death (2 pts). AOE occurred in 12 pts after a median duration of nilotinib treatment of 24 months (9-47). AOE included myocardial infarction (MI) or coronary heart disease (CHD) (n=3), cerebrovascular events (CeVD) (n=3) and peripheral artery disease (PAD) (n=6). Overall, the cumulative incidence of AOE was 2.91% (95% CI: 0.74-11.42) by 12 months, 9.81% (95% CI: 4.57-21.08) by 24 months, 19.29 (95% CI: 10.77-34.56) by 36 months and 27.7% (95% CI: 16.2-47.35) by 48 months (discontinuation of nilotinib and death as competing risks). Cumulative incidence of AOE by 48 months was 72.22% (95% CI: 47.46-100) in the H/VH group and only 12.13% (95% CI: 4.32-34.08) in the L/M group. Log Rank comparison of Kaplan Meier analysis of 48-month survival without AOE showed a significant difference between the 2 groups (27.78% (95% CI: 0-58.9) versus 84.38% (95% CI: 67.04-100) p=0.0001). Sensitivity of the ESC classification in nilotinib-treated patients was 67% and specificity 89%. It is important to note that all pts with a history of AOE had recurrent AOE on nilotinib. Nilotinib was discontinued in 11 pts with AOE after a median time of 288 days (1-688), 7 pts had recurrent or worsening AOE before nilotinib discontinuation and 2 pts died from AOE. Conclusions In our retrospective study, CVD risk estimation according to the 2012 ESC classification reveals that pts who belong to the H/VH risk group at baseline are at very high risk of AOE during nilotinib therapy. These findings now need to be validated in a prospective fashion. Nevertheless, we readily recommend that assessment of CVD risk should be performed in all pts considered for nilotinib therapy. Alternative TKI may be chosen whenever possible in pts at H/VH risk of CVD. In those treated with nilotinib, CVD risk should be reassessed throughout therapy and risk factors should be tightly controlled according to current guidelines. Disclosures: Rea: BMS: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; ARIAD: Honoraria; Teva: Honoraria. Messas:Novartis: Honoraria.

Background Nilotinib is approved for use in pts with CML after failure of imatinib and in newly diagnosed CP-CML. In the ENESTnd trial, 1st line nilotinib was associated with a higher frequency of hypercholesterolemia than imatinib. Moreover, several studies reported a nilotinib-associated risk of artery occlusive disease (AOD). In ENESTnd, pre-existing treatment for dyslipidemia did not preclude pts from enrolment. To avoid this pitfall and to determine which cholesterol fractions are affected and whether triglycerides (TG) are modified, we prospectively studied the plasma lipid profile of nilotinib-treated pts without drug treatment for dyslipidemia. Methods Pts (n=25) in our center with CP-CML either newly diagnosed or after failure of imatinib were proposed 1st or 2nd line nilotinib provided that neither very high risk for fatal cardiovascular disease (CVD) nor nilotinib-resistant ABL kinase domain mutation were present at baseline. Pts with drug treatment for dyslipidemia at baseline were excluded from this study. Total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and TG were measured prior to the start of nilotinib and at 3, 6, 9 and 12 months. Fasting glucose (FG) and glycosylated hemoglobin (HbA1C) were also measured. Results are shown as medians (min-max). ESC/EAS 2012 guidelines were used to determine CVD risk categories and for the management of dyslipidemias. Results Median age at nilotinib initiation was 52 years (19-69), 13 were males (52%). Sokal risk group was low in 11 pts (44%), intermediate in 11 (44%) and high in 3 (12%). Nilotinib was given upfront in 20 pts (80%) and after 1st line imatinib in 5 pts (20%). Median time from diagnosis was 0.8 month (0.4-4.3) in the former and 15.7 months (2.5-47.9) in the latter. Initial nilotinib dosing regimen was 300mg BID in 22 pts (88%) and 400mg BID in 3 pts (12%). Baseline CVD risk factors included age ≥ 45 years in men and ≥ 55 years in women in 33 pts (52%), active smoking or ceased during the previous year in 6 pts (24%), body mass index (BMI) ≥ 25 kg/m2in 14 pts (56%), hypertension in 1 pt (4%), type 2 diabetes mellitus (DM) in 1 pt (4%). Two pts were discovered pre DM. The CVD risk was low in 12 pts (48%), moderate in 11 pts (44%) and high in 2 pts (8%). At baseline, no pt required drug intervention by lipid lowering agents based on LDL-C, 11 pts (44%) had low HDL-C (≤0.4g/L) and 7 (28%) had high TG (≥1.5g/L). Median FG and HBA1C were 0.88g/L (0.63-1.26) and 5.5% (4.7-6.5), respectively. All pts were given lifestyle medical advice. At M3, TC, LDL-C and HDL-C had increased by a mean of 26.9%, 31.8% and 36.3%, respectively. Median TC at baseline and M3 was 1.84g/L (1.17-2.74) and 2.27g/L (1.08-3.62) (p Three pts (12%) required statins during the first year of nilotinib therapy: 2 pts with a moderate CVD risk at baseline and in whom LDL-C rose above 1.9g/L and 1 pt with a moderate CVD risk at baseline who developed peripheral artery disease (PAD) at M12, leading to nilotinib discontinuation. By M12, the CVD risk changed from low to high in 1 pt due do to the onset of DM and from moderate to very high in the pt with PAD. Conclusions Nilotinib is associated with a significant and early increase in TC, LDL-C and HDL-C. In contrast, a decrease in TG occurs but this may be due to lifestyle medical advice given to our patients. All patients considered for nilotinib therapy should have an evaluation of blood lipids at baseline and early after the start of therapy. Requirement for lifestyle modifications and lipid lowering treatment by statins should be determined at baseline and throughout therapy according to TC, LDL-C and CVD risk category. The role of nilotinib-induced high LDL-C in the onset of AOD needs to be investigated. Disclosures: Rea: Novartis: Honoraria; BMS: Honoraria; Teva: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Gautier:Novartis: Honoraria. Messas:Novartis: Honoraria. Dombret:Novartis: Research Funding.

Background—Autologous skeletal myoblast (SM) transplantation improves function of infarcted myocardium, but pretransplantation cultures remain a complex process. This study assessed whether it could be optimized by muscle preconditioning with the local anesthetic bupivacaine or even bypassed with the use of the so-called mince technique.Methods and Results—Muscle preconditioning consisted of intramuscular injections of the tibialis anterior of rats, 2 days before harvest. After 7 days of culture, the number of available myoblasts was significantly increased compared with nonconditioned controls (1 683 147 versus 85 300,P=0.0013). The mince technique was then assessed. A myocardial infarction was created in 66 rats by coronary artery ligation. One week later, rats were reoperated on and intramyocardially injected with culture medium alone (controls, n=23), autologous cultured SM (3.5×106, n=21), or autologous muscle minced into a fine slurry, which was immediately transplanted (n=22). All muscles had been preconditioned. Left ventricular function was assessed by 2D echocardiography. Whereas end-diastolic volumes expanded over time in all groups, left ventricular ejection fraction (%, mean±SEM) was increased only in the cultured SM–transplanted group at 1 (P=0.0006) and 2 months (P=0.0008) versus baseline (37.52±1.92 and 40.92±2.17 versus 30.34±1.74), with a significant additional benefit between 1 and 2 months (P=0.0069).Conclusions—Cell culture remains mandatory for SM transplantation to be successful but, in a clinical perspective, this process can be made more expeditious by preharvest muscle conditioning with bupivacaine, which greatly enhances the baseline cell yield.

Objectifs Rapporter le diagnostic rare et le traitement chirurgical d’un jeune patient present une dissection symptomatique de l’aorte abdominale revelant une arterite de Takayasu (TA). Methodes et resultats Une femme de 24 ans a developpe une dissection chronique douloureuse de l’aorte sous-renale avec une claudication des deux membres inferieurs. Comme la patiente restait symptomatique en depit d’un traitement medical optimal, on a propose une revascularisation chirurgicale. Un pontage aortobifemoral a ete fait avec resection de l’aorte sous-renale et le diagnostic histologique de TA. Conclusion La dissection aortique abdominale isolee est un evenement rare au cours d’une TA, et c’est le premier cas traite chirurgicalement. Peu de cas de dissection aortique avec TA ont ete publies, qui sont commentes dans cet article.

BackgroundIn ischemic mitral regurgitation (IMR), leaflet tethering is caused by post-MI LV and annular remodeling. Severing second-order mitral chordae significantly decreases tethering and MR. We tested whether undersized ring annuloplasty can improve chordal cutting efficacy by reducing annulus-related tethering.MethodsPosterolateral MI created chronic remodeling and MR in 28 sheep. At 3 months, sheep were randomized to sham surgery vs isolated annuloplasty undersized by 2 sizes vs isolated bileaflet chordal cutting vs at the combined therapy (n=7 each). At baseline, chronic MI (3 months) and sacrifice (6.6 months) we measured LV volumes and ejection fraction (EF), wall motion score index (WMSi), MR Regurgitation fraction (MRRF) and vena contracta (VC), Mitral annulus area (MAA) and posterior leaflet (PL) restriction angle (PL to MAA) by 2D and 3D echo.ResultsAll groups were comparable at baseline and chronic MI, with mild- moderate MR (MRVC 4.6±1.0mm, MRRF 24±2.6%) and MA dilatation (p