Impact of Anchor Location on Mitral Neochordae Forces: An In Vitro Study.

PURPOSE: This study examined changes in force distribution between the neochordae corresponding to different ventricular anchor locations. DESCRIPTION: Seven porcine mitral valves were mounted in a left heart simulator. Neochordae (expanded polytetrafluoroethylene) originated from either a simulated left ventricular apex, papillary muscle base, or papillary muscle tip location. The neochordae were attached at three sites along the P2 leaflet segment: P2Lateral; P2Center, and P2Medial. Mitral regurgitation was induced by cutting posterior leaflet P2 marginal chordae. The forces on each neochord required to restore normal mitral valve coaptation were quantified for different ventricular anchoring origins and leaflet insertion sites. EVALUATION: The results showed that under both normotensive and hypertensive conditions, the force exerted was much higher at P2Center than either P2Lateral or P2Medial, independent of ventricular anchor location. Also, forces on both P2Lateral and P2Medial were not statistically different. CONCLUSIONS: Artificial neochordae treatment for all anchoring locations was effective in correcting induced mitral regurgitation. The P2 central neochordae had a significantly higher force than both lateral neochords under all conditions.

Demonstration of proof-of-concept of StrokeShield system for complete closure and occlusion of the left atrial appendage for non-valvular atrial fibrillation therapy.

In the US, the most significant morbidity and mortality associated with non-valvular atrial fibrillation (NVAF) is embolic stroke, with 90% of thrombus originating from the left atrial appendage (LAA). Anticoagulation is the preferred treatment for the prevention of stroke in NVAF patients, but clinical studies have demonstrated high levels of non-compliance and increased risk of bleeding or ineligibility for anticoagulation therapy, especially in the elderly population where the incidence of NVAF is highest. Alternatively, stroke may be preventing using clinically approved surgical and catheter-based devices to exclude or occlude the LAA, but these devices continue to be plagued by peri-device leaks and thrombus formation because of residual volume. To overcome these limitations, Cor Habere (Louisville, KY) and the University of Louisville are developing a LAA closure device (StrokeShield) that completely occludes and collapses the LAA to minimize the risk of stroke. The StrokeShield device is a collapsible occluder (nitinol reinforced membrane) that completely covers the LAA orifice with an expandable conical coil anchor that attaches to the myocardium. The device is designed for catheter-based delivery and expands to completely occlude the LAA orifice and collapse the LAA. The primary advantages of the StrokeShield system are a completely sealed LAA (no peri-device flow or residual space) and smooth endothelialized connection to the left atrial wall with minimal risk of cardiac bleeding and tamponade. We tested proof-of-concept of a prototype StrokeShield device in acute (n = 2) and chronic 60-day (n = 2) healthy canine models. Acute results demonstrated that the conical coil securely attached to the myocardium (5N pull-out force) and the Nitinol umbrella fully deployed and covered the LAA ostium. Results from the chronic implants demonstrated long-term feasibility of device placement with no procedural or device-related intra- or post-operative complications, secure placement and correct positioning of the device with no device migration. The device successfully occluded the LAA ostium and collapsed the LAA with no interference with the mitral valve, circumflex coronary artery, or pulmonary veins. Necropsy demonstrated no gross signs of thrombus or end-organ damage and the device was encapsulated in the LAA. Histology demonstrated mature neointima covering the device with expected foreign body inflammatory response. These early positive results will help to guide the iterative design process for the continued development of the StrokeShield system.

New mitral annular force transducer optimized to distinguish annular segments and multi-plane forces.

Limited knowledge exists about the forces acting on mitral valve annuloplasty repair devices. The aim of this study was to develop a new mitral annular force transducer to measure the forces acting on clinically used mitral valve annuloplasty devices. The design of an X-shaped transducer in the present study was optimized for simultaneous in- and out-of-plane force measurements. Each arm was mounted with strain gauges on four circumferential elements to measure out-of-plane forces, and the central parts of the X-arms were mounted with two strain gauges to measure in-plane forces. A dedicated calibration setup was developed to calibrate isolated forces with tension and compression for in- and out-of-plane measurements. With this setup, it was possible with linear equations to isolate and distinguish measured forces between the two planes and minimize transducer arm crosstalk. An in-vitro test was performed to verify the crosstalk elimination method and the assumptions behind it. The force transducer was implanted and evaluated in an 80kg porcine in-vivo model. Following crosstalk elimination, in-plane systolic force accumulation was found to be in average 4.0±0.1N and the out-of-plane annular segments experienced an average force of 1.4±0.4N. Directions of the systolic out-of-plane forces indicated movements towards a saddle shaped annulus, and the transducer was able to measure independent directional forces in individual annular segments. Further measurements with the new transducer coupled with clinical annuloplasty rings will provide a detailed insight into the biomechanical dynamics of these devices.

Early feasibility testing and engineering development of a sutureless beating heart connector for left ventricular assist devices.

APK Advanced Medical Technologies (Atlanta, GA) is developing a sutureless beating heart (SBH) left ventricular assist device (LVAD) connector system consisting of anchoring titanium coil, titanium cannula with integrated silicone hemostatic valve, coring and delivery tool, and LVAD locking mechanism to facilitate LVAD inflow surgical procedures. Feasibility testing was completed in human cadavers (n = 4) under simulated normal and hypertensive conditions using saline to observe seal quality in degraded human tissue and assess anatomic fit; acutely in ischemic heart failure bovine model (n = 2) to investigate short-term performance and ease of use; and chronically for 30 days in healthy calves (n = 2) implanted with HeartWare HVAD to evaluate performance and biocompatibility. Complete hemostasis was achieved in human cadavers and animals at LV pressures up to 170 mm Hg. In animals, off-pump (no cardiopulmonary bypass) anchoring of the connector was accomplished in less than 1 minute with no residual bleeding after full delivery and locking of the LVAD; and implant of connector and LVAD were successfully completed in under 10 minutes with total procedure blood loss less than 100 ml. In chronic animals before necropsy, no signs of leakage or disruption at the attachment site were observed at systolic LV pressures >200 mm Hg.

In-vivo mitral annuloplasty ring transducer: implications for implantation and annular downsizing.

Mitral annuloplasty has been a keystone to the success of mitral valve repair in functional mitral regurgitation. Understanding the complex interplay between annular-ring stresses and left ventricular function has significant implications for patient-ring selection, repair failure, and patient safety. A step towards assessing these challenges is developing a transducer that can be implanted in the exact method as commercially available rings and can quantify multidirectional ring loading. An annuloplasty ring transducer was developed to measure stresses at eight locations on both the in-plane and out-of-plane surfaces of an annuloplasty ring's titanium core. The transducer was implanted in an ovine subject using 10 sutures at near symmetric locations. At implantation, the ring was observed to undersize the mitral annulus. The flaccid annulus exerted both compressive (-) and tensile stresses (+) on the ring ranging from -3.17 to 5.34 MPa. At baseline hemodynamics, stresses cyclically changed and peaked near mid-systole. Mean changes in cyclic stress from ventricular diastole to mid-systole ranged from -0.61 to 0.46 MPa (in-plane direction) and from -0.49 to 1.13 MPa (out-of-plane direction). Results demonstrate the variability in ring stresses that can be introduced during implantation and the cyclic contraction of the mitral annulus. Ring stresses at implantation were approximately 4 magnitudes larger than the cyclic changes in stress throughout the cardiac cycle. These methods will be extended to ring transducers of differing size and geometry. Upon additional investigation, these data will contribute to improved knowledge of annulus-ring stresses, LV function, and the safer development of mitral repair techniques.

Contractile mitral annular forces are reduced with ischemic mitral regurgitation.

OBJECTIVE: Forces acting on mitral annular devices in the setting of ischemic mitral regurgitation are currently unknown. The aim of this study was to quantify the cyclic forces that result from mitral annular contraction in a chronic ischemic mitral regurgitation ovine model and compare them with forces measured previously in healthy animals. METHODS: A novel force transducer was implanted in the mitral annulus of 6 ovine subjects 8 weeks after an inferior left ventricle infarction that produced progressive, severe chronic ischemic mitral regurgitation. Septal-lateral and transverse forces were measured continuously for cardiac cycles reaching a peak left ventricular pressure of 90, 125, 150, 175, and 200 mm Hg. Cyclic forces and their rate of change during isovolumetric contraction were quantified and compared with those measured in healthy animals. RESULTS: Animals with chronic ischemic mitral regurgitation exhibited a mean mitral regurgitation grade of 2.3 ± 0.5. Ischemic mitral regurgitation was observed to decrease significantly septal-lateral forces at each level of left ventricular pressure (P < .01). Transverse forces were consistently lower in the ischemic mitral regurgitation group despite not reaching statistical significance. The rate of change of these forces during isovolumetric contraction was found to increase significantly with peak left ventricular pressure (P < .005), but did not differ significantly between animal groups. CONCLUSIONS: Mitral annular forces were measured for the first time in a chronic ischemic mitral regurgitation animal model. Our findings demonstrated an inferior left ventricular infarct to decrease significantly cyclic septal-lateral forces while modestly lowering those in the transverse. The measurement of these forces and their variation with left ventricular pressure contributes significantly to the development of mitral annular ischemic mitral regurgitation devices.

Dynamic assessment of mitral annular force profile in an ovine model.

BACKGROUND: Limited knowledge exists regarding the forces that act on devices implanted in the mitral annulus. Determining the peak magnitudes, directions, rates, variation throughout the cardiac cycle, and change with left ventricular pressure (LVP) will aid in device development and evaluation. METHODS: Novel transducers with the ability to measure forces in the septal-lateral and transverse directions were implanted in six healthy ovine subjects. Forces were measured for cardiac cycles reaching a peak LVP of 90, 125, 150, 175, and 200 mm Hg. RESULTS: The septal-lateral force was observed to significantly increase from 3.9 ± 0.8 N (90) to 5.2 ± 1.0 N (125) p < 0.001, 5.9 ± 0.9 N (150) p < 0.001, 6.4 ± 1.2 N (175) p < 0.001, and 6.7 ± 1.5 N (200 mm Hg) p < 0.001. Similarly, the transverse force was seen to increase from 2.6 ± 0.6 N (90) to 3.8 ± 1.0 N (125) p < 0.01, 4.6 ± 1.3 N (150) p < 0.001, 4.3 ± 1.2 N (175) p < 0.001, and 3.5 ± 0.7 N (200 mm Hg) p < 0.05. In comparison, the septal-lateral force was significantly greater than the transverse force at 90 (p < 0.05), 125 (p < 0.05), 175 (p < 0.001), and 200 mm Hg (p < 0.0005). CONCLUSIONS: Annular forces and their variations with LVP through the cardiac cycle are described. The results demonstrate differences in force magnitude and rate for increasing levels of LVP between the septal-lateral and transverse directions. These directional differences have strong implications in the development of future mitral devices.

In-vivo transducer to measure dynamic mitral annular forces.

Limited knowledge exists regarding the forces which act on devices implanted to the heart's mitral valve. Developing a transducer to measure the peak force magnitudes, time rates of change, and relationship with left ventricular pressure will aid in device development. A novel force transducer was developed and implanted in the mitral valve annulus of an ovine subject. In the post-cardioplegic heart, septal-lateral and transverse forces were continuously measured for cardiac cycles reaching a peak left ventricular pressure of 90 mmHg. Each force was seen to increase from ventricular diastole and found to peak at mid-systole. The mean change in septal-lateral and transverse forces throughout the cardiac cycle was 4.4±0.2 N and 1.9±0.1 N respectively. During isovolumetric contraction, the septal-lateral and transverse forces were found to increase at peak rate of 143±8 N/s and 34±9 N/s, respectively. Combined, this study provides the first quantitative assessment of septal-lateral and transverse forces within the contractile mitral annulus. The developed transducer was successful in measuring these forces whose methods may be extended to future studies. Upon additional investigation, these data may contribute to the safer development and evaluation of devices aimed to repair or replace mitral valve function.

Transapical beating heart cardioscopy technique for off-pump visualization of heart valves.

OBJECTIVE: Endoscopic methods to perform intracardiac procedures are of enormous interest, with the introduction of transcatheter techniques for complex cardiac procedures. In the present study, we demonstrate the use of a novel transapical cardioscopy system to visualize intracardiac structures in a porcine model. METHODS: The cardioscope was designed to mount a miniature CCD camera at its tip and was covered in a blunt convex Plexiglass top that allowed displacement and visualization of the tissue in front of the cardioscope. Transapical access for 11-mm cardioscopy was performed by way of a median sternotomy (n = 4) and minithoracotomy (n = 1) in an anesthetized porcine model, and various cardiac structures were imaged under beating heart conditions. The images from the camera were projected onto a monitor for the operator to guide cardioscope positioning. RESULTS: Video images and identification of structures on the left side of an in vivo beating porcine heart were obtained. Initially, the papillary muscle and mitral valve components were evaluated. The left atrium was entered, and the pulmonary vein orifices and atrial appendage were confirmed. Next, the camera was positioned within the left ventricle, and the ventricular portion of the trileaflet aortic valve was inspected. Using direct visualization, the camera was passed into the proximal ascending aorta. The left and right coronary arteries were also visualized. A catheter was introduced by way of a side port to confirm the position of the aortic valve leaflets during visualization. The pig experienced no significant decrease in blood pressure and maintained a stable heart rate throughout the procedure. The port was removed, and the transapical incision was closed with minimal blood loss during the procedure and closure of the orifice. CONCLUSIONS: Transapical cardioscopy is a novel approach that allows for precise visualization of intracardiac structures within a beating porcine heart without the use of cardiopulmonary bypass. This technique might allow for more successful minimally invasive valvular, intracardiac, or ascending aortic procedures without the use of radiation.

In vitro characterization of the mechanisms responsible for functional tricuspid regurgitation.

BACKGROUND: Functional tricuspid regurgitation (TR) is increasingly recognized as a source of morbidity. Current repair strategies focus on annular remodeling because annular dilatation is common in patients with TR. Although papillary muscle (PM) displacement is recognized in functional mitral regurgitation, its role in TR is less well characterized. The objective of this in vitro study was to further clarify the mechanisms by which TR occurs as an effect of annular dilatation and PM displacement. METHODS AND RESULTS: Porcine tricuspid valves (n=16) were studied in an in vitro right heart simulator. The valve dynamics were quantified with isolated annular dilatation starting with a normal annular size (6 cm(2)) and incrementally dilated up to 100%, isolated PM displacement, and a combination of the 2. All valves lost competence at 40% dilatation, resulting in a TR of 7.9 ± 3.4 mL (P ≤ 0.05) compared with baseline and central residual leaflet length of 0.5 ± 0.2 cm. Multidirectional displacement of the anterior and posterior/septal PMs and all PMs significantly (P ≤ 0.05) increased TR, with normal annular area. Malcoaptation was observed where the 3 leaflets joined with all significant levels of TR. The anterior leaflet had the greatest percent change in residual leaflet length, whereas PM displacement caused a reduction in residual leaflet length for the septal leaflet for all conditions. CONCLUSIONS: This study shows that although annular dilatation alone leads to TR, isolated PM displacement can also cause TR; annular remodeling strategies should be tailored in the setting of severe PM displacement.

Saddle shape of the mitral annulus reduces systolic strains on the P2 segment of the posterior mitral leaflet.

BACKGROUND: The three-dimensional saddle shape of the mitral annulus is well characterized in animals and humans, but the impact of annular nonplanarity on valve function or mechanics is poorly understood. In this study, we investigated the impact of the saddle shaped mitral annulus on the mechanics of the P2 segment of the posterior mitral leaflet. METHODS: Eight porcine mitral valves (n = 8) were studied in an in-vitro left heart simulator with an adjustable annulus that could be changed from flat to different degrees of saddle. Miniature markers were placed on the atrial face of the posterior leaflet, and leaflet strains at 0%, 10%, and 20% saddle were measured using dual-camera stereophotogrammetry. Averaged areal strain and the principal strain components are reported. RESULTS: Peak areal strain magnitude decreased significantly from flat to 20% saddle annulus, with a 78% reduction in the measured strain over the entire P2 region. In the radial direction (annulus free edge), a 44.4% reduction in strain was measured, whereas in the circumferential direction (commissure-commissure), a 34% reduction was measured from flat to 20% saddle. CONCLUSIONS: Nonplanar shape of the mitral annulus significantly reduced the mechanical strains on the posterior leaflet during systolic valve closure. Reduction in strain in both the radial and circumferential directions may reduce loading on the suture lines and potentially improve repair durability, and also inhibit progression of valve degeneration in patients with myxomatous valve disease.

Cleft closure and undersizing annuloplasty improve mitral repair in atrioventricular canal defects.

OBJECTIVE: Reoperation rates to correct left atrioventricular valve regurgitation after primary repair of atrioventricular canal defects remain relatively high. The causes of valvular regurgitation are likely multifactorial, and simple cleft closure is often insufficient to prevent recurrence. METHODS: To elucidate the mechanisms leading to regurgitation, we conducted hemodynamic studies using isolated native mitral valves. Anatomy of these valves was altered to mimic atrioventricular canal type valves and studied under pediatric hemodynamic conditions. The impact of subvalvular geometry, cleft closure, annular dilatation, and annular undersizing on regurgitation were investigated. RESULTS: Papillary muscle position did not have a significant effect on regurgitation. Cleft closure had a significant impact on valvular competence, with reduction in regurgitation volume with increased cleft closure. Regurgitation volume decreased from 12.5 +/- 2.4 mL/beat for an open cleft to 4.9 +/- 1.9 mL/beat for a partially closed cleft and to 1.4 +/- 1.6 mL/beat when the cleft was completely closed. Annular dilatation had a significant impact on regurgitation even after cleft closure. A 40% increase in annular size increased regurgitation by 59% for a partially closed cleft and by 84% for a fully closed cleft. Reducing the annular size by 20% from the physiologic level decreased the regurgitation volume by 12% for a fully open cleft and by 58% for the partially closed cleft case. CONCLUSIONS: Annular dilatation after primary repair has a potentially significant role in the recurrence of atrioventricular valve regurgitation. Reducing the annular size and restricting dilatation as an adjunct to cleft closure is a promising surgical approach in such valve anatomies.

A saddle-shaped annulus reduces systolic strain on the central region of the mitral valve anterior leaflet.

OBJECTIVES: Mitral valve repair for degenerative diseases has shown suboptimal results in selected patients. Improved postinterventional mitral valve mechanics are essential to increase repair durability. METHODS: Eight porcine mitral valves were tested in a physiologic left heart simulator under normal hemodynamic conditions. Leaflet strain was measured by tracking the displacement of a 5 x 8 marker array located on the central region of the anterior leaflet. Local leaflet strain and strain rates were calculated from measured displacements. The experiments were conducted in 4 different annular configurations associated with saddle height/commissural diameter ratios of 0%, 10%, 20%, and 30%. All experiments were conducted in the normal papillary muscle position. RESULTS: For all annular configurations, the anterior leaflet material showed anisotropy, with the major principal strain in the radial direction and the minor principal strain in the circumferential direction. The peak major principal strain was 0.22 +/- 0.07, whereas the peak minor principal strain was 0.11 +/- 0.049 in the normal annular configuration (saddle height/commissural diameter ratio of 20%). The peak major principal strain was reduced by 13.52% +/- 12.79%, 27.53% +/- 13.65%, and 29.72% +/- 29.79% for the 10%, 20%, and 30% saddle height/commissural diameter ratio configurations, respectively, when compared with reduction for the flat annular configuration. Peak strain in the circumferential direction was unaffected by annular curvature. Reduction in areal strain of 18.62% +/- 18.98% and 27.97% +/- 35.01% were observed for the 20% and 30% saddle height/commissural diameter ratio configurations, respectively. CONCLUSION: The strain in the central region of the anterior leaflet is reduced with increasing annular saddle curvature. Decreased leaflet strain and associated stress might improve mitral valve repair durability.

Efficacy of the edge-to-edge repair in the setting of a dilated ventricle: an in vitro study.

BACKGROUND: The edge-to-edge repair to correct mitral regurgitation (MR) has shown substandard results in cases of ischemic MR or dilated cardiomyopathy. METHODS: Ten porcine mitral valves were investigated in a left heart simulator (120 mm Hg, 5 L/min). Pathologic conditions of a dilated ventricle were simulated by using an annular model capable of three levels of dilation (normal, 56%, and 120%) and by displacing papillary muscles (PMs) 10 mm in the apical, lateral, and posterior directions. The edge-to-edge repair was performed; a central stitch was investigated for symmetric and asymmetric PM displacements, and a paracommissural stitch was investigated for asymmetric PM displacements. Left ventricular pressure and mitral flow rate were monitored, and regurgitation fraction was calculated from the mitral flow curve. RESULTS: Under symmetric PM displacement, the repair reduced MR by 5.1% at dilation level one and by 9.1% at dilation level two. The repair decreased MR by 10.9% (dilation level two) after asymmetric displacement of the anterior-lateral PM, and by 5.4% (dilation level one) and 7.9% (dilation level two) after asymmetric displacement of the posterior-medial PM. The edge-to-edge repair reduced (p < 0.05) MR owing to annular dilation; however, it was unable to completely eliminate the MR. The repair did not significantly reduce MR caused by PM displacement, regardless of the displacement geometry. Stitch location did not affect repair efficacy. CONCLUSIONS: The edge-to-edge repair is not an effective procedure in correcting MR associated with PM displacement, although it is able to partially reduce MR caused by annular dilation.

Effects of annular size, transmitral pressure, and mitral flow rate on the edge-to-edge repair: an in vitro study.

BACKGROUND: Although edge-to-edge repair is an established adjunctive procedure, there is still debate on its long-term durability and efficacy. METHODS: Fifteen porcine mitral valves were studied in a physiologic left heart simulator with a variable size annulus (dilated = 8.22 cm2, normal = 6.86 cm2, contracted = 5.5 cm2). Mitral valves were tested under steady and physiologic pulsatile flow conditions (cardiac outputs: 4 to 6 L/min), at peak transmitral pressures between 100 mm Hg and 140 mm Hg. A miniature force transducer was used to measure the Alfieri stitch force (F(A)). Mitral flow rate (MFR), transmitral pressure, effective orifice area, mitral regurgitation, and F(A) were monitored. RESULTS: The edge-to-edge repair led to a decrease in effective orifice area of 16.55% +/- 8.22%; further reduction in effective orifice area was attained with annular contraction. Mitral regurgitation after the edge-to-edge repair was significantly higher (p <0.05) with annular dilation. In the pulsatile experiments, two peaks in F(A) were observed: one during systole (F(A) = 0.059 +/- 0.024 N) and a second during diastole (F(A) = 0.072 +/- 0.021 N). Multivariate analysis of variance analysis showed that during systole, transmitral pressure and mitral annular area (MAA) had significant effects on F(A) [F(A) = (4.40 x 10(-4)) transmitral pressure (mm Hg) + (5.0 x 10(-3)) MAA (cm2) - 0.05 (R2 = 0.80)], whereas during diastole MFR and MAA had significant effects on F(A) [F(A) = (1.03 x 10(-4)) MFR2 (L/min) - (1.60 x 10(-3)) MAA (cm2) + 0.02 (R2 = 0.90)]. CONCLUSIONS: With annular dilation, mitral regurgitation persisted even after the edge-to-edge repair. The edge-to-edge repair does not cause clinically relevant mitral valve stenosis in a normal size mitral valve. Mitral flow rate and transmitral pressure are the main determinants of F(A) during the cardiac cycle. Increasing annular area increases F(A) during systole but decreases F(A) during diastole. Systolic F(A) may become dominant with increases in MAA or peak transmitral pressure, or both.

Mechanics of the mitral valve: in vitro studies.

Improved knowledge of mitral valve (MV) mechanics is essential to understanding normal MV function and design; however, there is limited information about the mechanical properties of the MV during physiologic loading. These studies utilized different techniques to characterize the mechanical properties of the MV. Histological techniques were used to examine collagen, elastin, and cellular distribution on the chordae. Vessels were observed in both the longitudinal and circumferential directions. The presence of vessels characterize the chordae as complex living components that must work with the PM and MV leaflets to prevent MV prolapse and regurgitation. Force and strain distribution on the chordae and anterior leaflet were measured in a pathological papillary muscle (PM) positions. Tension distribution results showed that the intermediate chords on their respective leaflets. The slack PM position led to a delay in complete valve closure and more rapid leaflet loading in late systole. The chordae showed physiological strains, reaching maximum strain during valve closure. The in vitro studies demonstrated that chordal force distribution and valve function depend on the mechanical environment of the valve and the geometric relationships between its components.