Wolfgang Bothe

Material properties of the ovine mitral valve anterior leaflet in vivo from inverse finite element analysis

We measured leaflet displacements and used inverse finite-element analysis to define, for the first time, the material properties of mitral valve (MV) leaflets in vivo. Sixteen miniature radiopaque markers were sewn to the MV annulus, 16 to the anterior MV leaflet, and 1 on each papillary muscle tip in 17 sheep. Four-dimensional coordinates were obtained from biplane videofluoroscopic marker images (60 frames/s) during three complete cardiac cycles. A finite-element model of the anterior MV leaflet was developed using marker coordinates at the end of isovolumic relaxation (IVR; when the pressure difference across the valve is approximately 0), as the minimum stress reference state. Leaflet displacements were simulated during IVR using measured left ventricular and atrial pressures. The leaflet shear modulus (G(circ-rad)) and elastic moduli in both the commisure-commisure (E(circ)) and radial (E(rad)) directions were obtained using the method of feasible directions to minimize the difference between simulated and measured displacements. Group mean (+/-SD) values (17 animals, 3 heartbeats each, i.e., 51 cardiac cycles) were as follows: G(circ-rad) = 121 +/- 22 N/mm2, E(circ) = 43 +/- 18 N/mm2, and E(rad) = 11 +/- 3 N/mm2 (E(circ) > E(rad), P < 0.01). These values, much greater than those previously reported from in vitro studies, may result from activated neurally controlled contractile tissue within the leaflet that is inactive in excised tissues. This could have important implications, not only to our understanding of mitral valve physiology in the beating heart but for providing additional information to aid the development of more durable tissue-engineered bioprosthetic valves.

Stress-Strain Behavior of Mitral Valve Leaflets in the Beating Ovine Heart

Excised anterior mitral leaflets exhibit anisotropic, non-linear material behavior with pre-transitional stiffness ranging from 0.06 to 0.09 N/mm(2) and post-transitional stiffness from 2 to 9 N/mm(2). We used inverse finite element (FE) analysis to test, for the first time, whether the anterior mitral leaflet (AML), in vivo, exhibits similar non-linear behavior during isovolumic relaxation (IVR). Miniature radiopaque markers were sewn to the mitral annulus, AML, and papillary muscles in 8 sheep. Four-dimensional marker coordinates were obtained using biplane videofluoroscopic imaging during three consecutive cardiac cycles. A FE model of the AML was developed using marker coordinates at the end of isovolumic relaxation (when pressure difference across the valve is approximately zero), as the reference state. AML displacements were simulated during IVR using measured left ventricular and atrial pressures. AML elastic moduli in the radial and circumferential directions were obtained for each heartbeat by inverse FEA, minimizing the difference between simulated and measured displacements. Stress-strain curves for each beat were obtained from the FE model at incrementally increasing transmitral pressure intervals during IVR. Linear regression of 24 individual stress-strain curves (8 hearts, 3 beats each) yielded a mean (+/-SD) linear correlation coefficient (r(2)) of 0.994+/-0.003 for the circumferential direction and 0.995+/-0.003 for the radial direction. Thus, unlike isolated leaflets, the AML, in vivo, operates linearly over a physiologic range of pressures in the closed mitral valve.

Implantation of the permanent Jarvik-2000 left ventricular assist device: A single-center experience

OBJECTIVES We sought to evaluate the surgical results and effects of continuous support with the permanent Jarvik-2000 left ventricular assist device (LVAD). We report the early outcomes. BACKGROUND A shortage of transplant donors necessitates the testing of alternative treatments. The Jarvik-2000 is an axial flow pump with a percutaneous retro-auricular power connector, designed for permanent use. METHODS Patients with severe heart failure (HF), unsuitable for heart transplantation or conventional LVAD support, were offered implantation. The surgical approach included a left lateral thoracotomy. The device was implanted into the left ventricular apex on femoro-femoral bypass. It is set to allow pulsatile flow with an aortic valve opening. Anticoagulation is adjusted the same as for patients with a heart valve. RESULTS Between May 2001 and August 2001, we implanted the Jarvik-2000 in two patients with dilated cardiomyopathy and in one with cardiac amyloidosis, all with severe HF (cardiac index 1.8 +/- 0.3 l/m(2) per min). One patient required preoperative inotropic support. All patients did well, with no repeat operations or infections. Patients received 4.3 +/- 3.2 packed red blood cells and were intubated at 14 +/- 3 h, and the intensive care unit stay was 7.0 +/- 0.5 days. The cardiac index increased from 3.7 +/- 1.5 l/min per m(2) at 8,000 rpm to 5.9 +/- 2.9 l/min per m(2) at 12,000 rpm. All patients currently have mild hemolysis not requiring transfusion. The following postoperative events were recorded: a transient ischemic attack with complete recovery, a short re-intubation due to ventricular arrhythmia, loss of consciousness with a battery change while standing, knee-joint effusion after ergometry training, a minor wound problem and a short hospital re-admission due to dehydration. Patients were discharged home after 49 +/- 7 days; one has returned to work. All quality-of-life scores have improved. CONCLUSIONS The permanent Jarvik-2000 appears safe. It can be used for dilative or restrictive disease. The Jarvik-2000 might prove a valid option for the long-term treatment of patients with severe HF.

Therapy with insulin in cardiac surgery: controversies and possible solutions.

Insulin has been used in the treatment of patients undergoing cardiac surgery or suffering from acute myocardial infarction. Most of these investigations have demonstrated that the metabolic cocktail consisting of glucose-insulin-potassium (GIK) improves recovery of function and outcome after cardiac surgery and substantially reduces mortality of patients with acute myocardial infarction. There is also evidence suggesting that insulin is not effective under these conditions, as demonstrated in a recent large randomized trial in cardiac surgery. It is therefore not surprising that insulin or GIK is not used routinely in clinical practice. Many hypotheses have been advanced to explain the effects of insulin and GIK but none of them has enjoyed convincing support. In cardiac surgery the many different application protocols described make it difficult to compare the results. The application of GIK after cardiac surgery may be complicated by severe disturbances in glucose or potassium homeostasis. In this article we review the literature in this field, addressing the areas of controversy. We discuss the different mechanisms suggested and we propose potential solutions. We conclude that a multifactorial mechanism is likely to explain the effects of insulin or GIK after ischemia and we propose that in a practical sense the application of high-dose insulin during reperfusion, utilizing a newly described, direct nonmetabolic effect, is a convincing concept. We will further demonstrate our clinical experience in establishing a protocol for putting this concept into clinical practice.

Mitral Valve Annuloplasty A Quantitative Clinical and Mechanical Comparison of Different Annuloplasty Devices

Mitral valve annuloplasty is a common surgical technique used in the repair of a leaking valve by implanting an annuloplasty device. To enhance repair durability, these devices are designed to increase leaflet coaptation, while preserving the native annular shape and motion; however, the precise impact of device implantation on annular deformation, strain, and curvature is unknown. In this article, we quantify how three frequently used devices significantly impair native annular dynamics. In controlled in vivo experiments, we surgically implanted 11 flexible-incomplete, 11 semi-rigid-complete, and 12 rigid-complete devices around the mitral annuli of 34 sheep, each tagged with 16 equally spaced tantalum markers. We recorded four-dimensional marker coordinates using biplane videofluoroscopy, first with device and then without, which were used to create mathematical models using piecewise cubic splines. Clinical metrics (characteristic anatomical distances) revealed significant global reduction in annular dynamics upon device implantation. Mechanical metrics (strain and curvature fields) explained this reduction via a local loss of anterior dilation and posterior contraction. Overall, all three devices unfavorably caused reduction in annular dynamics. The flexible-incomplete device, however, preserved native annular dynamics to a larger extent than the complete devices. Heterogeneous strain and curvature profiles suggest the need for heterogeneous support, which may spawn more rational design of annuloplasty devices using design concepts of functionally graded materials.

In-vivo dynamic strains of the ovine anterior mitral valve leaflet

Understanding the mechanics of the mitral valve is crucial in terms of designing and evaluating medical devices and techniques for mitral valve repair. In the current study we characterize the in vivo strains of the anterior mitral valve leaflet. On cardiopulmonary bypass, we sew miniature markers onto the leaflets of 57 sheep. During the cardiac cycle, the coordinates of these markers are recorded via biplane fluoroscopy. From the resulting four-dimensional data sets, we calculate areal, maximum principal, circumferential, and radial leaflet strains and display their profiles on the averaged leaflet geometry. Average peak areal strains are 13.8±6.3%, maximum principal strains are 13.0±4.7%, circumferential strains are 5.0±2.7%, and radial strains are 7.8±4.3%. Maximum principal strains are largest in the belly region, where they are aligned with the circumferential direction during diastole switching into the radial direction during systole. Circumferential strains are concentrated at the distal portion of the belly region close to the free edge of the leaflet, while radial strains are highest in the center of the leaflet, stretching from the posterior to the anterior commissure. In summary, leaflet strains display significant temporal, regional, and directional variations with largest values inside the belly region and toward the free edge. Characterizing strain distribution profiles might be of particular clinical significance when optimizing mitral valve repair techniques in terms of forces on suture lines and on medical devices.

Active stiffening of mitral valve leaflets in the beating heart.

The anterior leaflet of the mitral valve (MV), viewed traditionally as a passive membrane, is shown to be a highly active structure in the beating heart. Two types of leaflet contractile activity are demonstrated: 1) a brief twitch at the beginning of each beat (reflecting contraction of myocytes in the leaflet in communication with and excited by left atrial muscle) that is relaxed by midsystole and whose contractile activity is eliminated with beta-receptor blockade and 2) sustained tone during isovolumic relaxation, insensitive to beta-blockade, but doubled by stimulation of the neurally rich region of aortic-mitral continuity. These findings raise the possibility that these leaflets are neurally controlled tissues, with potentially adaptive capabilities to meet the changing physiological demands on the heart. They also provide a basis for a permanent paradigm shift from one viewing the leaflets as passive flaps to one viewing them as active tissues whose complex function and dysfunction must be taken into account when considering not only therapeutic approaches to MV disease, but even the definitions of MV disease itself.

Characterization of mitral valve annular dynamics in the beating heart

The objective of this study is to establish a mathematical characterization of the mitral valve annulus that allows a precise qualitative and quantitative assessment of annular dynamics in the beating heart. We define annular geometry through 16 miniature markers sewn onto the annuli of 55 sheep. Using biplane videofluoroscopy, we record marker coordinates in vivo. By approximating these 16 marker coordinates through piecewise cubic splines, we generate a smooth mathematical representation of the 55 mitral annuli. We time-align these 55 annulus representations with respect to characteristic hemodynamic time points to generate an averaged baseline annulus representation. To characterize annular physiology, we extract classical clinical metrics of annular form and function throughout the cardiac cycle. To characterize annular dynamics, we calculate displacements, strains, and curvature from the discrete mathematical representations. To illustrate potential future applications of this approach, we create rapid prototypes of the averaged mitral annulus at characteristic hemodynamic time points. In summary, this study introduces a novel mathematical model that allows us to identify temporal, regional, and inter-subject variations of clinical and mechanical metrics that characterize mitral annular form and function. Ultimately, this model can serve as a valuable tool to optimize both surgical and interventional approaches that aim at restoring mitral valve competence.

Rigid, Complete Annuloplasty Rings Increase Anterior Mitral Leaflet Strains in the Normal Beating Ovine Heart

Background— Annuloplasty ring or band implantation during surgical mitral valve repair perturbs mitral annular dimensions, dynamics, and shape, which have been associated with changes in anterior mitral leaflet (AML) strain patterns and suboptimal long-term repair durability. We hypothesized that rigid rings with nonphysiological three-dimensional shapes, but not saddle-shaped rigid rings or flexible bands, increase AML strains. Methods and Results— Sheep had 23 radiopaque markers inserted: 7 along the anterior mitral annulus and 16 equally spaced on the AML. True-sized Cosgrove-Edwards flexible, partial band (n=12), rigid, complete St Jude Medical rigid saddle-shaped (n=12), Carpentier-Edwards Physio (n=12), Edwards IMR ETlogix (n=11), and Edwards GeoForm (n=12) annuloplasty rings were implanted in a releasable fashion. Under acute open-chest conditions, 4-dimensional marker coordinates were obtained using biplane videofluoroscopy along with hemodynamic parameters with the ring inserted and after release. Marker coordinates were triangulated, and the largest maximum principal AML strains were determined during isovolumetric relaxation. No relevant changes in hemodynamics occurred. Compared with the respective control state, strains increased significantly with rigid saddle-shaped annuloplasty ring, Carpentier-Edwards Physio, Edwards IMR ETlogix, and Edwards GeoForm (0.14±0.05 versus 0.16±0.05, P=0.024, 0.15±0.03 versus 0.18±0.04, P=0.020, 0.11±0.05 versus 0.14±0.05, P=0.042, and 0.13±0.05 versus 0.16±0.05, P=0.009), but not with Cosgrove-Edwards band (0.15±0.05 versus 0.15±0.04, P=0.973). Conclusions— Regardless of three-dimensional shape, rigid, complete annuloplasty rings, but not a flexible, partial band, increased AML strains in the normal beating ovine heart. Clinical studies are needed to determine whether annuloplasty rings affect AML strains in patients, and, if so, whether ring-induced perturbations in leaflet strain states are linked to repair failure.

Sizing for Mitral Annuloplasty: Where Does Science Stop and Voodoo Begin?

The implantation of an improperly sized annuloplasty ring may result in an incompetent valve after surgical mitral valve repair. Consequently, the procedure of ring size selection is considered critical. Although a plethora of sizing strategies are described, the opinions on how to select the appropriate ring size differ widely and often appear arbitrary (ie, without scientific justification). These inconsistencies raise the question where, with respect to ring sizing, science stops and voodoo begins.