Creation of nonischemic functional mitral regurgitation by annular dilatation and nonplanar modification in a chronic in vivo swine model.
ABSTRACT: Mechanisms and treatments of nonischemic functional mitral regurgitation (NIMR) are not fully established, in part, because of a lack of proper large animal models. We developed a novel technique of NIMR creation in a swine model by making multiple small incisions in the mitral annulus.Ex vivo experiments using isolated swine hearts (n=10) showed a 15% increase in annular area (6.8-7.8 cm(2)) after 16 incisions were made along the posterior mitral annulus of a pressurized left ventricle. In an in vivo swine model (n=7; 46.4 ± 2.2 kg), NIMR was created by making fourteen to twenty-six 2-mm incisions in the atrial aspect of the mitral annulus using a cardioport video-assisted imaging system in the beating heart. Animals were euthanized at 4 weeks (n=4) and 6 weeks (n=3). Three-dimensional (3D) echocardiography was obtained before and immediately after NIMR creation and at euthanasia; vena contracta area, mitral annular dimension, left ventricular volume, and inter-papillary muscle distance were measured. The mitral annular incisions resulted in mild to moderate mitral regurgitation and an increased vena contracta area. NIMR creation altered mitral valve geometry by decreasing mitral annular nonplanarity and increasing annular area, primarily in the anteroposterior dimension. NIMR creation did not significantly change left ventricular volume or inter-papillary muscle distance. Longer follow-up period did not significantly affect these outcomes.NIMR can successfully be created in a beating heart swine model and results in dilatation and 3D changes in mitral annular geometry. This model can enhance the experimental validation of new valve repair devices and techniques.
Project description:Recently, there has been increased interest in minimally invasive mitral valve prolapse repair techniques; however, these techniques have limitations. A new technique was developed for treating mitral valve prolapse that uses a novel leaflet plication clip to selectively plicate the prolapsed leaflet segment. The clip's efficacy was tested in an animal model.Yorkshire pigs (n = 7) were placed on cardiopulmonary bypass (CPB), and mitral valve prolapse was created by cutting chordae supporting the P2 segment of the posterior leaflet. Animals were weaned off CPB and mitral regurgitation (MR) was assessed echocardiographically. CPB was reinitiated and the plication clip was applied under direct vision to the P2 segment to eliminate the prolapse. The animals survived for 2 hours. Epicardial echocardiography was obtained before and after prolapse creation and 2 hours after clip placement to quantify MR grade and vena contracta area. Posterior leaflet mobility and coaptation height were analyzed before and after clip placement.There were no cases of clip embolization. Median MR grade increased from trivial (0-1.5) to moderate-severe after MR creation (2.5-4+) (P < .05), and decreased to mild after clip placement (0-3+) (P < .05). Vena contracta area tended to increase after cutting the chordae and decrease after clip placement: 0.08 ± 0.10 cm(2) versus 0.21 ± 0.15 cm(2) versus 0.16 ± 0.16 cm(2) (P = .21). The plication clip did not impair leaflet mobility. Coaptation height was restored to baseline: 0.51 ± 0.07 cm versus 0.44 ± 0.18 cm (P = 1.0).The leaflet plication clip can treat mitral valve prolapse in an animal model, restoring coaptation height without affecting leaflet mobility. This approach is a simple technique that may improve the effectiveness of beating-heart and minimally invasive valve surgery.
Project description:The extent of mitral annular (MA) remodeling and dysfunction is correlated with the severity of mitral regurgitation (MR) as well as left atrial (LA) and left ventricular (LV) dilation. MA dysfunction may be a useful prognostic factor for operative timing and MR recurrence after successful mitral valve (MV) repair. The aim of this study was to evaluate additive prognostic factors of MA non-planarity using real-time 3D transesophageal echocardiography (RT3D-TEE) analysis in patients with chronic severe MR and preserved LV systolic function.Forty-seven patients with chronic severe MR and preserved LV systolic function scheduled for MV repair were prospectively enrolled. Echocardiographic studies were performed before surgery and postoperatively within 2 weeks and at least 6 months after surgery. RT3D-TEE was performed before the operation and immediately post-operative.Mean age was 55.4 ± 15.1 years and 24 were male. Annulus height/body surface area (BSA) obtained via RT3D-TEE was correlated with the degree of postoperative LA remodeling. Patients were divided into two groups by average baseline annulus height/BSA. Patients with normal annular height had a smaller postoperative LV end-diastolic dimension, LV end-systolic dimension and LA volume index than patients with decreased annular height. Preoperative annulus height/BSA values strongly predicted postoperative LA remodeling.MA height may be a useful prognostic factor for determining the timing of surgery in patients with chronic primary MR. Annulus height/BSA assessed via RT3D-TEE may provide additional information predictive of postoperative LA remodeling after successful MV repair.
Project description:remodeling of the mitral annulus contributes to progression of mitral regurgitation (MR). In patients with moderate-to-severe MR, short-term treatment with ?-blockers has been shown to increase left ventricular (LV) end-diastolic and end-systolic volume, and this could deleteriously increase mitral valve annular dimensions. The objective of this study was to quantify the effects of a short duration of ?-blocker treatment on mitral annular dimensions and dynamics in patients with MR due to primary degenerative valve disease.twenty-five patients with moderate-to-severe degenerative MR and normal LV systolic function were studied in a double-blind crossover experiment using a ?1-selective adrenergic blocker and placebo administered for 14±3 days. Cardiac MRI images were acquired after each treatment period to quantify mitral annular dimensions. At end diastole, there was no change in annular area (1659±331 versus 1632±299 mm(2); P<0.19), annular perimeter (154.3±16.4 versus 152±13.9 mm; P<0.13), septal-lateral (SL) dimension (38.0±5 versus 39.0±4.5 mm; P<0.15), or annular height (9.8±3.8 versus 9.5±2.5 mm; P<0.53). ?-blockade resulted in significant end-diastole decreases in commissure-commissure dimension (48.9±4.6 versus 47.2±4.0 mm; P<0.01) and eccentricity (1.3±0.2 versus 1.2±0.1; P<0.01). At end systole (ES), ?-blockade conferred a small, but significant decrease in annular perimeter (161.0±19.3 versus 156.8±16.9 mm; P<0.04) and eccentricity (1.2±0.1 versus 1.1±0.1; P<0.02), and the SL dimension significantly increased (41.5±5.7 versus 43.0±5.3 mm; P<0.03). Commissure-commissure dimension, annular area, and annular height at ES were not significantly different.despite significant increases in LV end-diastolic and end-systolic volume, short-term ?-blocker treatment of patients with moderate-to-severe MR reduced or preserved all mitral annular dimensions except SL at ES.
Project description:OBJECTIVES:This study hypothesized that compensatory mitral leaflet area (MLA) adaptation occurs in patients with persistent atrial fibrillation (AF) without left ventricular (LV) dysfunction but has limitations that augment mitral regurgitation (MR). The study also explored whether asymmetrical annular dilation is matched by relative leaflet enlargement. BACKGROUND:Functional MR occurs in patients with AF and isolated annular dilation, but the relationship of MLA adaptation with annular area (AA) is unknown. METHODS:Three-dimensional echocardiographic images were acquired from 86 patients with quantified MR: 53 with nonvalvular persistent AF (23 MR+ with moderate or greater MR, 30 MR-) without LV dysfunction or dilation and 33 normal controls. Comprehensive 3-dimensional analysis included total diastolic MLA, adaptation ratios of MLA to annular area and MLA to leaflet closure area, and annular and tenting geometry. RESULTS:Total MLA was 22% larger in patients with AF than in controls, thus paralleling the increased AA. However, as AA increased, adaptive indices (MLA/AA ratio and ratio of MLA to closure area) plateaued, becoming lowest in MR+ patients (ratio of MLA to closure area = 1.63 ± 0.17 controls, 1.60 ± 0.11 MR-, 1.32 ± 0.10 MR+; p < 0.001). MR increased as the ratio of MLA to closure area decreased (R2 = 0.68; p < 0.001). The posterior-to-anterior MLA ratio remained constant, whereas the posterior-to-anterior mitral annulus perimeter increased (1.21 ± 0.16 controls, 1.32 ± 0.20 MR-, 1.46 ± 0.19 MR+; p < 0.001). Multivariate MR determinants were annular area, total MLA to closure area, and posterior-to-anterior perimeter ratios. CONCLUSIONS:MLA adaptively increases in AF with isolated annular dilation and normal LV function. This compensatory enlargement becomes insufficient with greater annular dilation, and the leaflets fail to match asymmetrical annular remodeling, thereby increasing MR. These findings can potentially help optimize therapeutic options and motivate basic studies of adaptive growth processes.
Project description:Accurate quantification of mitral regurgitation (MR) is important for patient treatment and prognosis. Three-dimensional echocardiography allows for the direct measure of the regurgitant orifice area (ROA) by 3D-guided planimetry of the vena contracta area (VCA). We aimed to (1) establish 3D VCA ranges and cutoff values for MR grading, using the American Society of Echocardiography-recommended 2D integrative method as a reference, and (2) compare 2D and 3D methods of ROA to establish a common calibration for MR grading.Eighty-three patients with at least mild MR underwent 2D and 3D echocardiography. Direct planimetry of VCA was performed by 3D echocardiography. Two-dimensional quantification of MR included 2D ROA by proximal isovelocity surface area (PISA) method, vena contracta width, and ratio of jet area to left atrial area. There were significant differences in 3D VCA among patients with different MR grades. As assessed by receiver operating characteristic analysis, 3D VCA at a best cutoff value of 0.41 cm(2) yielded 97% of sensitivity and 82% of specificity to differentiate moderate from severe MR. There was significant difference between 2D ROA and 3D VCA in patients with functional MR, resulting in an underestimation of ROA by 2D PISA method by 27% as compared with 3D VCA. Multivariable regression analysis showed functional MR as etiology was the only predictor of underestimation of ROA by the 2D PISA method.Three-dimensional VCA provides a single, directly visualized, and reliable measurement of ROA, which classifies MR severity comparable to current clinical practice using the American Society of Echocardiography-recommended 2D integrative method. The 3D VCA method improves accuracy of MR grading compared with the 2D PISA method by eliminating geometric and flow assumptions, allowing for uniform clinical grading cutoffs and ranges that apply regardless of etiology and orifice shape.
Project description:Real-time three-dimensional transesophageal echocardiography has increased our understanding of the distinct pathomechanisms underlying functional, ischaemic or degenerative mitral regurgitation. However, potential differences in dynamic morphology between the subtypes of degenerative mitral prolapse have scarcely been investigated.In order to compare the dynamic behavior of the different phenotypes of degenerative mitral valve prolapse, real-time three-dimensional transesophageal echocardiography recordings of 77 subjects, 27 with Barlow disease (BD), 32 with Fibroelastic deficiency (FED) and 18 normal controls (NC) were analysed.Geometric annular and valvular parameters of the myxomatous patients were significantly larger compared to controls (BD vs. FED vs. NC 3D annular area: 15 ± 2.8 vs. 13.3 ± 2.4 vs. 10.6 ± 2.3cm(2), all p < 0.01). Beside similar ellipticity, BD annuli were significantly flatter compared to FED. Myxomatous annuli appeared less dynamic than normals, with decreased overall 3D area change, however only the BD group differed from NC significantly (BD vs. FED vs. NC normalized 3D area change 4.40 vs. 6.81 vs. 9.69 %; BD vs. NC p = 0.000; FED vs. NC p = not significant, BD vs. FED p = 0.025).BD and FED differ not only in terms of valve morphology, but also annular dynamics. Both pathologies are characterized by annular dilatation. However, in BD the annulus is remarkably flattened and hypodynamic, whereas in FED its saddle-shape and contractile function is relatively preserved. These features might influence the choice of repair technique and the selection of annuloplasty ring.
Project description:We developed and tested a novel transcatheter circumferential annuloplasty technique to reduce mitral regurgitation in porcine ischemic cardiomyopathy.Catheter-based annuloplasty for secondary mitral regurgitation exploits the proximity of the coronary sinus to the mitral annulus, but is limited by anatomic variants and coronary artery entrapment.The procedure, "cerclage annuloplasty," is guided by magnetic resonance imaging (MRI) roadmaps fused with live X-ray. A coronary sinus guidewire traverses a short segment of the basal septal myocardium to re-enter the right heart where it is exchanged for a suture. Tension is applied interactively during imaging and secured with a locking device.We found 2 feasible suture pathways from the great cardiac vein across the interventricular septum to create cerclage. Right ventricular septal re-entry required shorter fluoroscopy times than right atrial re-entry, which entailed a longer intramyocardial traversal but did not cross the tricuspid valve. Graded tension progressively reduced septal-lateral annular diameter, but not end-systolic elastance or regional myocardial function. A simple arch-like device protected entrapped coronary arteries from compression even during supratherapeutic tension. Cerclage reduced mitral regurgitation fraction (from 22.8 +/- 12.7% to 7.2 +/- 4.4%, p = 0.04) by slice tracking velocity-encoded MRI. Flexible cerclage reduced annular size but preserved annular motion. Cerclage also displaced the posterior annulus toward the papillary muscles. Cerclage introduced reciprocal constraint to the left ventricular outflow tract and mitral annulus that enhanced leaflet coaptation. A sample of human coronary venograms and computed tomography angiograms suggested that most have suitable venous anatomy for cerclage.Transcatheter mitral cerclage annuloplasty acutely reduces mitral regurgitation in porcine ischemic cardiomyopathy. Entrapped coronary arteries can be protected. MRI provided insight into the mechanism of cerclage action.
Project description:The aim of this study was to examine the chronic effects of polyvinyl-alcohol (PVA) injection on mitral regurgitation (MR) reduction, mitral valve geometry, and left ventricular (LV) remodeling in a chronic ischemic MR sheep model.Previous studies have demonstrated acute efficacy of PVA hydrogel polymer injection into infarcted myocardium underlying the papillary muscle to relieve MR by papillary muscle repositioning. However, the chronic efficacy of PVA injection in the chronic infarction setting remains unclear.Sixteen sheep developed chronic MR 8 weeks after induced inferoposterior myocardial infarction. Ten consecutive sheep underwent PVA injection (PVA group) and 6 sheep served as control subjects with saline injection. Epicardial 2-/3-dimensional echocardiography was performed at the baseline, chronic MR (pre-injection), and sacrifice (8 weeks after injection) stages.Both groups were comparable at the baseline and chronic MR stages. At sacrifice, MR decreased from moderate to trace or mild (vena contracta: 0.17 ± 0.08 cm vs. 0.56 ± 0.10 cm, p < 0.001) in the PVA group but progressed to moderate to severe in the control group. End-systolic and -diastolic volumes remained stable in the PVA group but increased significantly in the control group (both p < 0.05). At sacrifice, compared with the control group, the PVA group had significantly less left ventricular remodeling (end-systolic volume: 41.1 ± 10.4 ml vs. 55.9 ± 12.4 ml, p < 0.05), lower MR severity (vena contracta: 0.17 ± 0.08 cm vs. 0.60 ± 0.14 cm, p < 0.01), and favorable changes in mitral valve geometry.Polymer injection in a chronic ischemic MR model results in persistent reduction of MR and attenuation of continued left ventricular remodeling over 8 weeks of follow-up.
Project description:Progressive superior shift of the mitral valve (MV) during systole is associated with abnormal papillary muscle (PM) superior shift in late systolic MV prolapse (MVP). The causal relation of these superior shifts remains unclarified. We hypothesized that the MV superior shift is related to augmented MV superiorly pushing force by systolic left ventricular pressure due to MV annular dilatation, which can be corrected by surgical MV plasty, leading to postoperative disappearance of these superior shifts. In 35 controls, 28 patients with holosystolic MVP, and 28 patients with late systolic MVP, the MV coaptation depth from the MV annulus was measured at early and late systole by two-dimensional echocardiography. The PM tip superior shift was monitored by echocardiographic speckle tracking. MV superiorly pushing force was obtained as MV annular area?×?(systolic blood pressure - 10). Measurements were repeated after MV plasty in 14 patients with late systolic MVP. Compared with controls and patients with holosystolic MVP, MV and PM superior shifts and MV superiorly pushing force were greater in patients with late systolic MVP [1.3 (0.5) vs. 0.9 (0.6) vs. 3.9 (1.0) mm/m2, 1.3 (0.5) vs. 1.2 (1.0) vs. 3.3 (1.3) mm/m2, and 487 (90) vs. 606 (167) vs. 742 (177) mmHg·cm2·m-2, respectively, means (SD), P < 0.001]. MV superior shift was correlated with PM superior shift ( P < 0.001), which was further related to augmented MV superiorly pushing force ( P < 0.001). MV and PM superior shift disappeared after surgical MV plasty for late systolic MVP. These data suggest that MV annulus dilatation augmenting MV superiorly pushing force may promote secondary superior shift of the MV (equal to late systolic MVP) that causes subvalvular PM traction in patients with late systolic MVP. NEW & NOTEWORTHY Late systolic mitral valve prolapse (MVP) is associated with mitral valve (MV) and papillary muscle (PM) abnormal superior shifts during systole, but the causal relation remains unclarified. MV and PM superior shifts were correlated with augmented MV superiorly pushing force by annular dilatation and disappeared after surgical MV plasty with annulus size and MV superiorly pushing force reduction. This suggests that MV annulus dilatation may promote secondary superior shifts of the MV (late systolic MVP) that cause subvalvular PM traction.
Project description:BACKGROUND:Catheter-tissue contact force is an important factor influencing lesion size and efficacy and thereby potential for arrhythmia recurrence following accessory pathway (AP) radiofrequency ablation. We aim to evaluate adequacy and perception of catheter contact on the tricuspid and mitral annuli. METHODS:Data were collected from 42 patients undergoing catheter ablation. Operators were blinded to contact force information and reported perceived contact (poor, moderate, or good) while positioning the catheter at four tricuspid annular sites (12, 9, 6 and 4 o'clock positions; abbreviated as TA12, TA9, TA6 and TA4) and three mitral annular sites (3, 5 and 7 o'clock positions; abbreviated as MA3, MA5 and MA7) through long vascular sheaths. RESULTS:The highest and lowest mean contact forces were obtained at MA7 (13.3 ± 1.7 g) and TA12 (3.6 g ± 1.3 g) respectively. Mean contact force on tricuspid annulus (6.1 g ± 0.9 g) was lower than mitral annulus (9.8 ± 0.9 g) locations (p = 0.0036), with greater proportion of sites with <10 g contact force (81.7% vs 60.4%; p = 0.0075). Perceived contact had no impact on measured mean contact force for both mitral and tricuspid annular positions (p = 0.959 and 0.671 respectively). There was correlation of both impedance and atrial electrogram amplitude with contact force, though insufficient to be clinically applicable. CONCLUSION:A high proportion of annular catheter applications have low contact force despite being performed with long vascular sheaths in the hands of experienced operators. In addition, there was no impact of operator perceived contact force on actual measured contact force. This may carry implications for success of AP ablation.