D C Miller’s research while affiliated with Stanford University and other places

Objective: To evaluate the role of commissure orientation on downstream blood flow patterns and ascending aortic wall shear stress (WSS) in patients with bicuspid aortic valves (BAV) after valve-sparing aortic root replacement (V-SARR). Methods: Nineteen BAV patients after V-SARR (9 Sievers' type 1/LR [type 1 valve with fusion of the left and right cusps] and 10 Sievers' type 0/LAT [''naturally perfect''; type 0 valve without the presence of a raphe, and with the 2 commissures oriented right-anterior-to-left-posterior]) were imaged using time-resolved 3-D phase contrast magnetic resonance imaging. A control group of 5 unoperated tricuspid aortic valve patients were used for comparison purposes. Wall shear stress and eccentricity of flow normalized to aortic diameter were measured in planes placed perpendicular to the axis of the ascending aorta at the level of the sinotubular junction (proximal ascending), main pulmonary artery (mid-ascending), and origin of the brachiocephalic (distal ascending).

Aims: Recent annuloplasty ring annuloplasty ring designs to treat functional/ischemic mitral regurgitation (FMR/IMR) include disproportionate downsizing of the septal-lateral (S-L) mitral annular dimension to maximize mitral leaflet coaptation, intending also to reshape the dilated, spherical left ventricle (LV). The study objective was to quantify the effects of different disease-specific FMR/IMR ring types on LV sphericity during acute myocardial ischemia in the beating ovine heart. Methods: In thirty adult sheep radiopaque markers were placed as opposing pairs on the S-L and anterior-posterior (A-P) aspects of the mitral annulus (ANN) and the basal level of the LV (Fig, A). Ten true-sized Carpentier-Edwards Physio 1, Edwards IMR ETLogix, and GeoForm annuloplasty rings were inserted in a releasable fashion. ARs were true-sized by assessing the bare area of the anterior mitral leaflet. Under acute open chest conditions 4-D marker coordinates were obtained using biplane videofluoroscopy with ring inserted at baseline (data not shown) and after 90 seconds of left circumflex artery occlusion (RING_ISCH). After ring release, another dataset was acquired before (data not shown) and after left circumflex artery occlusion (No_Ring_ISCH). S-L and A-P diameters for ANN and LV were computed as the distances between the respective marker pairs at end-diastole. Sphericity was calculated by dividing S-L diameters by A-P diameters. Results: While all ring types significantly reduced mitral annular (ANN) sphericity, none of the ring types altered the sphericity of the LV (Fig, B). Fig. 1: Bothe LV sphericity w rings DGTHG 2013 Conclusion: These findings from the acutely ischemic ovine heart indicate that disease-specific FMR/IMR annuloplasty rings may not be effective in restoring a more elliptical LV shape in patients with FMR/IMR and LV dilatation.

Objective: It has recently been proposed that cusp configuration of the bicuspid aortic valve (BAV, Sievers' type 0 [S0] or 1 [S1]) might have an impact on functional outcome, valve durability, and reoperation after valve-sparing aortic root replacement (V-SARR). We tested this hypothesis retrospectively. Methods: 74 BAV-patients (59 male, age 45±10 years) underwent V-SARR (T. David-V) from 2000 to 2011. Detailed BAV-configuration was documented intra-operatively. Follow-up TTE was done early and late post-operatively (6±3 days and 2.9±1.7 years, respectively, cumulative follow-up=172 patient-years). Patients were grouped according to their Sievers' BAV configuration. Kaplan-Meier, logrank calculations and Cox proportional hazards models were used to compare functional valvular outcome between groups (endpoints: Freedom from 1+ AR, 2+ AR, and AR progression) and test continuous covariates' impact on post-operative valvular function. Results: 50 patients had S1-BAV (n=44 RL, n=4 RN, n=2 NL) and 24 had S0-BAV. 54 BAV had AR, 20 were normal, and none were stenotic. At eight years, overall survival was 98.6%, freedom from reoperation 96% and freedom from infectious complications 98.6%. Overall freedom from AR progression at five years was 47%, and 35% at seven years (40% for S1-BAV, 60% for S0-BAV). 18 patients (24%) had AR progression (20% of S0-BAV and 26% of S1-BAV), increasing from no or trace AR to AR 1+ (n=15) and to AR 2+ (n=3). Freedom from AR grades higher than 2+ at eight years was 100%. As by Cox Model, covariates including annular size (mean preop. 28±3mm) and annular diameter reduction (mean 4.7±3.3mm) per se did not significantly affect AR progression (p=0.6). Presence of a regurgitant S1-BAV was linked to higher rate of progressive AR (p=0.017) and higher rate of 1+ AR (p=0.008) when compared to others. Conclusion: The “naturally perfect” S0-BAV (2 sinuses, 2 cusps, 2 commissures) is the best substrate for V-SARR. The “majority type” S1- BAV, especially when associated with annular dilatation and AR, is associated with a higher likelihood of mid-term functional valve deterioration. Longer-term investigation is needed to evaluate fully the impact of BAV configuration on late valvular and clinical outcome after V-SARR.

The implantation of annuloplasty rings is a common surgical treatment targeted to re-establish mitral valve competence in patients with mitral regurgitation. It is hypothesized that annuloplasty ring implantation influences leaflet curvature, which in turn may considerably impair repair durability. This research is driven by the vision to design repair devices that optimize leaflet curvature to reduce valvular stress. In pursuit of this goal, the objective of this manuscript is to quantify leaflet curvature in ovine models with and without annuloplasty ring using in vivo animal data from videofluoroscopic marker analysis. We represent the surface of the anterior mitral leaflet based on 23 radiopaque markers using subdivision surfaces techniques. Quartic box-spline functions are applied to determine leaflet curvature on overlapping subdivision patches. We illustrate the virtual reconstruction of the leaflet surface for both interpolating and approximating algorithms. Different scalar-valued metrics are introduced to quantify leaflet curvature in the beating heart using the approximating subdivision scheme. To explore the impact of annuloplasty ring implantation, we analyze ring-induced curvature changes at characteristic instances throughout the cardiac cycle. The presented results demonstrate that the fully automated subdivision surface procedure can successfully reconstruct a smooth representation of the anterior mitral valve from a limited number of markers at a high temporal resolution of approximately 60 frames per minute.

Rapid early diastolic left ventricular (LV) filling requires a highly compliant chamber immediately after systole, allowing inflow at low driving pressures. The transmural LV deformations associated with such filling are not completely understood. We sought to characterize regional transmural LV strains during diastole, with focus on early filling, in ovine hearts at 1 week and 8 weeks after myocardial marker implantation. In seven normal sheep hearts, 13 radiopaque markers were inserted to silhouette the LV chamber and a transmural beadset was implanted into the lateral equatorial LV wall to measure transmural strains. Four-dimensional marker dynamics were obtained 1 week and 8 weeks thereafter with biplane videofluoroscopy in closed-chest, anesthetized animals. LV transmural strains in both cardiac and fiber-sheet coordinates were studied from filling onset to the end of early filling (EOEF, 100 ms after filling onset) and at end diastole. At the 8 week study, subepicardial circumferential strain (ECC) had reached its final value already at EOEF, while longitudinal and radial strains were nearly zero at this time. Subepicardial ECC and fiber relengthening (Eff) at EOEF were reduced to 1 compared with 8 weeks after surgery (ECC:0.02+/-0.01 to 0.08+/-0.02 and Eff:0.00+/-0.01 to 0.03+/-0.01, respectively, both P<0.05). Subepicardial ECC during early LV filling was associated primarily with fiber-normal and sheet-normal shears at the 1 week study, but to all three fiber-sheet shears and fiber relengthening at the 8 week study. These changes in LV subepicardial mechanics provide a possible mechanistic basis for regional myocardial lusitropic function, and may add to our understanding of LV myocardial diastolic dysfunction.

Mitral annular (MA) excursion during diastole encompasses a volume that is part of total left ventricular (LV) filling volume (LVFV). Altered excursion or area variation of the MA due to changes in preload or inotropic state could affect LV filling. We hypothesized that changes in LV preload and inotropic state would not alter the contribution of MA dynamics to LVFV. Six sheep underwent marker implantation in the LV wall and around the MA. After 7-10 days, biplane fluoroscopy was used to obtain three-dimensional marker dynamics from sedated, closed-chest animals during control conditions, inotropic augmentation with calcium (Ca), preload reduction with nitroprusside (N), and vena caval occlusion (VCO). The contribution of MA dynamics to total LVFV was assessed using volume estimates based on multiple tetrahedra defined by the three-dimensional marker positions. Neither the absolute nor the relative contribution of MA dynamics to LVFV changed with Ca or N, although MA area decreased (Ca, P < 0.01; and N, P < 0.05) and excursion increased (Ca, P < 0.01). During VCO, the absolute contribution of MA dynamics to LVFV decreased (P < 0.001), based on a reduction in both area (P < 0.001) and excursion (P < 0.01), but the relative contribution to LVFV increased from 18 +/- 4 to 45 +/- 13% (P < 0.001). Thus MA dynamics contribute substantially to LV diastolic filling. Although MA excursion and mean area change with moderate preload reduction and inotropic augmentation, the contribution of MA dynamics to total LVFV is constant with sizeable magnitude. With marked preload reduction (VCO), the contribution of MA dynamics to LVFV becomes even more important.