Frederick A. Tibayan

Geometric Distortions of the Mitral Valvular-Ventricular Complex in Chronic Ischemic Mitral Regurgitation

Background—Better understanding of the precise 3-dimensional geometric changes of the mitral valvular-ventricular complex in chronic ischemic mitral regurgitation (CIMR) is needed in order to devise better surgical repair techniques. We hypothesized that changes after inferior myocardial infarction would be different in hearts that developed CIMR compared with those that did not. Methods and Results—Twenty-four sheep underwent coronary snare and marker placement (annulus, papillary muscles, and anterior and posterior leaflets). After 8 days, cinefluoroscopy provided 3-dimensional marker data, and snare occlusion of obtuse marginal branches created inferior myocardial infarction, including the posterior papillary muscle. After 7 weeks, the 16 surviving animals were studied again and grouped by mitral regurgitation grade (≥ 2+, n=10 versus ≤ 1+, n=6). End-systolic mitral annulus dimensions, components of papillary muscle and leaflet displacement, were calculated. After inferior myocardial infarction, total displacement of the posterior papillary muscle from the midseptal annulus (“saddle horn”) was greater in CIMR(+) animals: 6.5±3.2 versus 3.1±2.7 (P =0.02), with the posterior papillary muscle moving more laterally (6.8±3.4 versus 2.5±3.5 mm, P =0.01). Increase in mitral annular septal-lateral diameter was greater in animals with CIMR (4.9±2.7 versus 2.3±2.0, P =0.02), and apical displacement of the posterior leaflet (PL) margin was also greater in the CIMR(+) group (1.7±1.0 versus 0.3±0.5, P =0.01). Conclusions—The CIMR(+) group had greater septal-lateral annular dilatation, lateral posterior papillary muscle displacement, and apical PL restriction, indicating that these associated geometric alterations may be important in the pathogenesis of CIMR. Treatment of CIMR should address both annular septal-lateral dilatation and lateral displacement of the posterior papillary muscle.

Importance of Mitral Valve Second-Order Chordae for Left Ventricular Geometry, Wall Thickening Mechanics, and Global Systolic Function

Background—Mitral valvular–ventricular continuity is important for left ventricular (LV) systolic function, but the specific contributions of the anterior leaflet second-order “strut” chordae are unknown. Methods and Results—Eight sheep had radiopaque markers implanted to silhouette the LV, annulus, and papillary muscles (PMs); 3 transmural bead columns were inserted into the mid-lateral wall between the PMs. The strut chordae were encircled with exteriorized wire snares. Three-dimensional marker images and hemodynamic data were acquired before and after chordal cutting. Preload recruitable stroke work (PRSW) and end-systolic elastance (Ees) were calculated to assess global LV systolic function (n=7). Transmural strains were measured from bead displacements (n=4). Chordal cutting caused global LV dysfunction: Ees (1.48±1.12 versus 0.98±1.30 mm Hg/mL, P=0.04) and PRSW (69±16 versus 60±15 mm Hg, P=0.03) decreased. Although heart rate and time from ED to ES were unchanged, time of mid-ejection was delayed (125±18 versus 136±19 ms, P=0.01). Globally, the LV apex and posterior PM tip were displaced away from the fibrous annulus and LV base-apex length increased at end-diastole and end-systole (all +1 mm, P<0.05). Locally, subendocardial end-diastolic strains occurred: Longitudinal strain (E22) 0.030±0.013 and radial thickening (E33) 0.081±0.041 (both P<0.05 versus zero). Subendocardial systolic shear strains were also perturbed: Circumferential-longitudinal “micro-torsion” (E12) (0.099±0.035 versus 0.075±0.025) and circumferential radial shear (E13) (0.084±0.023 versus 0.039±0.008, both P<0.05). Conclusion—Cutting second-order chords altered LV geometry, remodeled the myocardium between the PMs, perturbed local systolic strain patterns affecting micro-torsion and wall-thickening, and caused global systolic dysfunction, demonstrating the importance of these chordae for LV structure and function.

Alterations in Left Ventricular Torsion and Diastolic Recoil After Myocardial Infarction With and Without Chronic Ischemic Mitral Regurgitation

Background—Chronic ischemic mitral regurgitation (CIMR) is associated with heart failure that continues unabated whether the valve is repaired, replaced, or ignored. Altered left ventricular (LV) torsion dynamics, with deleterious effects on transmural gradients of oxygen consumption and diastolic filling, may play a role in the cycle of the failing myocardium. We hypothesized that LV dilatation and perturbations in torsion would be greater in animals in which CIMR developed after inferior myocardial infarction (MI) than in those that it did not. Methods—8±2 days after marker placement in sheep, 3-dimensional fluoroscopic marker data (baseline) were obtained before creating inferior MI by snare occlusion. After 7±1 weeks, the animals were restudied (chronic). Inferior MI resulted in CIMR in 11 animals but not in 9 (non-CIMR). End-diastolic septal-lateral and anterior-posterior LV diameters, maximal torsional deformation (&phgr;max, rotation of the LV apex with respect to the base), and torsional recoil in early diastole (&phgr;5%, first 5% of filling) for each LV free wall region (anterior, lateral, posterior) were measured. Results—Both CIMR and non-CIMR animals demonstrated derangement of LV torsion after inferior MI. In contrast to non-CIMR, CIMR animals exhibited greater LV dilation and significant reductions in posterior maximal torsion (6.1±4.3° to 3.9±1.9°* versus 4.4±2.5° to 2.8±2.0°; mean±SD, baseline to chronic, *P<0.05) and anterior torsional recoil (−1.4±1.1° to −0.2±1.0° versus −1.2±1.0° to −1.3±1.6°). Conclusion—MI associated with CIMR resulted in greater perturbations in torsion and recoil than inferior MI without CIMR. These perturbations may be linked to more LV dilation in CIMR, which possibly reduced the effectiveness of fiber shortening on torsion generation. Altered torsion and recoil may contribute to the “ventricular disease” component of CIMR, with increased gradients of myocardial oxygen consumption and impaired diastolic filling. These abnormalities in regional torsion and recoil may, in part, underlie the “ventricular disease” of CIMR, which may persist despite restoration of mitral competence.

Undersized mitral annuloplasty alters left ventricular shape during acute ischemic mitral regurgitation.

Background—Underlying left ventricular (LV) dysfunction contributes to poor survival after operation to correct ischemic mitral regurgitation (IMR). Many surgeons do not appreciate that a key component of the Bolling undersized mitral ring annuloplasty concept is to decrease LV wall stress by altering LV shape, but precise 3-dimensional (3-D) geometric data do not exist substantiating this effect. We tested the hypothesis that annular reduction decreases regional circumferential LV radius of curvature (ROC) in a model of acute IMR. Methods—Eight adult sheep underwent insertion of an adjustable Paneth-type annuloplasty suture and radiopaque markers on the LV and mitral annulus. The animals were studied with biplane videofluoroscopy during baseline conditions, then before and after tightening the annuloplasty suture during proximal left circumflex occlusion. End-systolic circumferential regional LV ROC and mitral annular area were computed. Results—Acute IMR was eliminated (MR grade 2.1±0.4 to 0.4±0.4, mean±SD, P<0.05) by tightening the Paneth annuloplasty suture. Paneth suture tightening during circumflex occlusion also decreased end-systolic regional circumferential radii of curvature at the basal (anterior, 3.40±0.16 to 3.34±0.14 cm; posterior, 3.31±0.23 to 3.24±0.26 cm; P<0.05) and equatorial levels (anterior, 2.99±0.21 to 2.89±0.29 cm; posterior, 2.86±0.38 to 2.81±0.41 cm; P<0.05). Conclusions—Acute proximal circumflex occlusion caused IMR and increased end-systolic LV radii of curvature in this experimental preparation. Annular reduction sufficient to abolish IMR also decreased end-systolic anterior and posterior LV ROC, which would be expected to reduce LV wall stress and oxygen consumption in these regions, both potentially beneficial effects. The long-term effects of undersized annuloplasty on LV remodeling and function, however, will require further study in chronic animal preparations or patients with chronic IMR.

Edge-to-edge mitral valve repair without ring annuloplasty for acute ischemic mitral regurgitation

BackgroundAlfieri edge-to-edge mitral repair has been used clinically with ring annuloplasty to correct ischemic mitral regurgitation (IMR), but its efficacy without concomitant ring annuloplasty has not been described in this setting. MethodsSeventeen sheep underwent implantation of 9 radiopaque markers on the left ventricle, 8 on the mitral annulus (MA), 1 on each papillary muscle (PM) tip, and 1 on the anterior and posterior leaflet edges near the anterior and posterior commissures. Alfieri repair was performed in 7 animals, and 10 were controls. Biplane videofluoroscopy and transesophageal echocardiography (TEE) were performed (open chest) before and continuously during left circumflex coronary artery occlusion to induce acute IMR. MA area (MAA), anterior (APM), and posterior (PPM) papillary muscle tip distances to midseptal MA (“saddle horn”), and distance of each leaflet marker to the mitral annular plane were calculated from 3-dimensional marker coordinates at end-systole (ES). ResultsSeverity of IMR was not different between groups (+1.9±0.7 versus +1.4±0.5 for Control and Alfieri, respectively; P =not significant [NS]). Mitral annular area (MAA; 21±15 versus 19±9%; P =NS) and septal-lateral (SL) annular diameter (12±6 versus 12±11%; P =NS) increased similarly during ischemia. While PPM-saddle horn distance increased in both groups (1.5±1.3 and 1.6±1.4 mm for Control and Alfieri, respectively; P <0.05 versus preischemia), APM-saddle horn distance increased in Control (1.0±1.2 mm; P =0.03) but not in the Alfieri animals (0.8±08 mm; P =0.07). Leaflet edge displacements from the annular plane during ischemia were similar in both groups. ConclusionsAlfieri repair did not prevent acute IMR nor alter ischemic valvular or subvalvular geometric perturbations. Adjunct surgical procedures, such as ring annuloplasty, are also necessary.

Evidence of adaptive mitral leaflet growth

Ischemic mitral regurgitation is mitral insufficiency caused by myocardial infarction. Recent studies suggest that mitral leaflets have the potential to grow and reduce the degree of regurgitation. Leaflet growth has been associated with papillary muscle displacement, but role of annular dilation in leaflet growth is unclear. We tested the hypothesis that chronic leaflet stretch, induced by papillary muscle tethering and annular dilation, triggers chronic leaflet growth. To decipher the mechanisms that drive the growth process, we further quantified regional and directional variations of growth. Five adult sheep underwent coronary snare and marker placement on the left ventricle, papillary muscles, mitral annulus, and mitral leaflet. After eight days, we tightened the snares to create inferior myocardial infarction. We recorded marker coordinates at baseline, acutely (immediately post-infarction), and chronically (five weeks post-infarction). From these coordinates, we calculated acute and chronic changes in ventricular, papillary muscle, and annular geometry along with acute and chronic leaflet strains. Chronic left ventricular dilation of 17.15% (p<0.001) induced chronic posterior papillary muscle displacement of 13.49 mm (p=0.07). Chronic mitral annular area, commissural and septal-lateral distances increased by 32.50% (p=0.010), 14.11% (p=0.007), and 10.84% (p=0.010). Chronic area, circumferential, and radial growth were 15.57%, 5.91%, and 3.58%, with non-significant regional variations (p=0.868). Our study demonstrates that mechanical stretch, induced by annular dilation and papillary muscle tethering, triggers mitral leaflet growth. Understanding the mechanisms of leaflet adaptation may open new avenues to pharmacologically or surgically manipulate mechanotransduction pathways to augment mitral leaflet area and reduce the degree of regurgitation.

Cutting second-order chords does not prevent acute ischemic mitral regurgitation.

Background—Cutting anterior mitral leaflet second-order chordae has been proposed for repair in ischemic mitral regurgitation (IMR). We examined the efficacy of such chordal cutting in preventing acute IMR. Methods and Results—Six sheep underwent radiopaque marker placement (left ventricle, mitral annulus, papillary muscles [PMs], and leaflets). The largest second-order chord from each PM was encircled with exteriorized wire snares. Three-dimensional marker coordinates were obtained with biplane videofluoroscopy before and during acute ischemia (80 seconds of mid-circumflex occlusion). Color Doppler transesophageal echocardiography was used to grade MR on a 0 to 4+ scale. Data were acquired immediately before and after dividing second-order chordae. Slope of the end-diastolic volume–stroke work relationship (PRSW) was calculated to assess systolic function. Chordal cutting increased anterior leaflet inflection angle (155±12 versus 162±9 degrees; P=0.03), resulting in a flatter leaflet, but did not increase effective leaflet length (1.97±0.24 versus 2.08±0.23 cm; P=0.15); PRSW decreased (63±15 versus 56±12 mm Hg; P=0.008). Both before and after chordal cutting, ischemia caused: Septal–lateral annular dilation (P=0.005), posterior PM displacement away from the mid-septal annulus (P=0.06), increased leaflet tenting area (P=0.001), and increased leaflet tenting volume (P=0.002). Before chordal cutting, MR increased significantly during ischemia (0.5±0.3 versus 1.7±0.4; P<0.001), and IMR increased similarly even after the second-order chords were cut (0.7±0.4 versus 1.9±0.9; P<0.001). Conclusions—Cutting second-order chordae resulted in LV systolic dysfunction and neither prevented nor decreased the severity of acute IMR, septal–lateral annular dilation, leaflet tenting area, or leaflet tenting volume.

The effects of mitral annuloplasty rings on mitral valve complex 3-D geometry during acute left ventricular ischemia

OBJECTIVE Annuloplasty rings are used to treat ischemic mitral regurgitation (IMR), but their exact effects on 3-D geometry of the overall mitral valve complex during acute left ventricular (LV) ischemia remain unknown. METHODS Radiopaque markers were sutured to the mitral leaflet edges, annulus, papillary muscle tips, and ventricle in three groups of sheep. One group served as control (n = 5), and the others underwent Duran (n = 6) or Physio (n = 5) ring annuloplasty. One week later, 3-D marker coordinates at end-systole were obtained before and during balloon occlusion of the circumflex artery. RESULTS In all control animals, acute LV ischemia was associated with: (i) septal-lateral separation of the leaflet edges, which was predicted by lateral displacement of the lateral annulus during septal-lateral mitral annular dilatation; (ii) apical restriction of the posterior leaflet edge, which was predicted by displacement of the lateral annulus away from the non-ischemic anterior papillary muscle; (iii) displacement of the posterior papillary muscle, which was not predictive of either septal-lateral leaflet separation or leaflet restriction; and (iv) mitral regurgitation. In the Duran group during ischemia, the posterior leaflet edge shifted posteriorly due to posterior movement of the lateral annulus, but no IMR occurred. In the Physio group during ischemia, neither the posterior leaflet edge nor the lateral annulus changed positions, and there was no IMR. In both the Duran and Physio groups, displacement of the posterior papillary muscle did not lead to IMR. CONCLUSIONS Either annuloplasty ring prevented the perturbations of mitral leaflet and annular--but not papillary muscle tip--3-D geometry during acute LV ischemia. By fixing the septal-lateral annular dimension and preventing lateral displacement of the lateral annulus, annuloplasty rings prevented systolic septal-lateral leaflet separation and posterior leaflet restriction, and no acute IMR occurred. The flexible ring allowed posterior displacement of the posterior leaflet edge and the lateral annulus, which was not observed with a semi-rigid ring.

Impact of Single-Ventricle Physiology on Death After Heart Transplantation in Adults With Congenital Heart Disease

BACKGROUND Prevalence of univentricular (1V) anatomy over time and whether 1V anatomy is associated with early death after heart transplant (HTx) among recipients with adult congenital heart disease (ACHD) is unknown. We investigated changes in case-mix over time, 1V vs biventricular (2V) status, and the effect of 1V anatomy on death after HTx among ACHD recipients. METHODS The Nationwide Inpatient Sample (NIS) was used to identify ACHD HTx recipients in the United States aged 14 years or older from 1993 to 2007, divided into era 1 (1993 to 2000) and era 2 (2001 to 2007). In-hospital death was compared among recipients with 1V and 2V anatomy. Multivariable determinants associated with an increased risk of in-hospital death were sought with logistic regression models. RESULTS From a national estimate of 509 ACHD recipients, 143 were 1V and 366 were 2V. Overall, 1V in-hospital mortality (23%) was higher than for 2V (8%; p<0.001) and remained associated with in-hospital death after adjustment for other factors (odds ratio, 3.9; 95% confidence interval, 1.29 to 11.74; p=0.02). All 1V diagnoses had higher mortality than all 2V diagnoses. Despite minor fluctuations, the proportion of 1V patients did not increase over time (era 1, 36%; era 2, 30%; p=0.46). CONCLUSIONS Overall case-mix of ACHD recipients (1V vs 2V) has not changed over time. Initial 1V anatomy increases post-HTx death among ACHD recipients, whereas 2V patients have mortality rates similar to non-CHD recipients. National and international transplant registries should include specific CHD diagnoses because this factor plays such a large role in determining early outcomes.

Mechanical Circulatory Support Pathways That Maximize Post-Heart Transplant Survival

BACKGROUND Heart transplant (HTx) recipients reach transplantation through increasing numbers of support pathways, including transition from one pathway to another. Outcomes of patients successfully bridged with various support pathways are unknown. We sought to identify mechanical circulatory support pathways that maximize survival after HTx. METHODS A supplemented United Network Organ Sharing Dataset tracked status 1 HTx outcomes from 2000 to 2010. Recipients were grouped based on support pathway before HTx, including those transitioning from one pathway to another. Multivariable factors for time-related death were sought using Cox proportional hazard regression models. RESULTS We identified 13,250 status 1 HTx recipients. Initial support pathways were inotropes (n = 7,607), left ventricular assist device (LVAD [n = 4,034]), intraaortic balloon pump (n = 729), biventricular assist device (n = 521), extracorporeal membrane oxygenation (ECMO [n = 316]), and right ventricular assist device (n = 43). Multivariable analysis demonstrated that LVAD use conferred a survival advantage (hazard ratio [HR] 0.71; p < 0.001), whereas all other support pathways, including inotropes (HR 1.1; p = 0.02), right ventricular assist device (HR 1.9; p = 0.01), and ECMO (HR 2.2; p < 0.001) increased the risk of post-HTx death. Support pathway transition (both escalation and reduction) occurred in 2,175 patients. Patients who transitioned from either ECMO or biventricular assist device support at listing to LVAD-only support at HTx had improved post-HTx survival that was comparable to patients who had LVAD-only therapy throughout their course (p = 0.74). CONCLUSIONS The LVAD supported HTx recipients have better posttransplant survival than patients after all other mechanical support pathways. Survival after HTx is optimized when ECMO or biventricular assist device support can be transitioned to LVAD-only support. Our findings should aid clinical decision making and inform organ allocation policy development intended to maximize societal benefits of HTx.