A Swine Model of Percutaneous Intracoronary Ethanol Induced Acute Myocardial Infarction and Ischemic Mitral Regurgitation.

Ischemic mitral regurgitation (IMR) is a frequent complication after a myocardial infarction (MI), which doubles mortality. Transcatheter mitral repairs are emerging as alternative treatment options to open heart surgery for IMR, but animal models to test them are lacking. We report a percutaneous swine model of IMR. Seventeen swine were randomized to (group 1, n = 12) MI causing IMR, and (group 2, n = 5) controls. In group 1, MI was induced via percutaneous ethanol injection into the obtuse marginal branches of the left circumflex artery, resulting in ST elevating myocardial infarction. Nine animals were survived to 8-10 weeks with weekly echocardiograms and three swine were survived to 16-20 weeks with MRI at termination. In group 1 animals, average IMR fraction at termination was 26.6 ± 2.3% in the echo group, and 24.51 ± 0.41% in the MRI group. None of the animals in group 2 had IMR. Left ventricular dysfunction and significant dilatation were evident in group 1 animals, compared to the controls. In conclusion, a reproducible model of IMR is reported for use in pre-clinical testing of new mitral technologies.

Swine (Sus scrofa) as a Model of Postinfarction Mitral Regurgitation and Techniques to Accommodate Its Effects during Surgical Repair.

Mitral regurgitation (MR) is a common heart-valve lesion after myocardial infarction in humans. Because it is considered a risk factor for accelerated heart failure and death, various surgical approaches and catheter-based devices to correct it are in development. Lack of a reproducible animal model of MR after myocardial infarction and reliable techniques to perform open-heart surgery in these diseased models led to the use of healthy animals to test new devices. Thus, most devices that are deemed safe in healthy animals have shown poor results in human efficacy studies, hampering progress in this area of research. Here we report our experience with a swine model of postinfarction MR, describe techniques to induce regurgitation and perform open-heart surgery in these diseased animals, and discuss our outcomes, complications, and solutions.

The Impact of Intimal Tear Location and Partial False Lumen Thrombosis in Acute Type B Aortic Dissection.

BACKGROUND: Partial false lumen (FL) thrombosis is a risk factor for long-term mortality in acute type B aortic dissection (ATBAD). This study investigates FL pressures in models of ATBAD with patent and partially thrombosed FL. METHODS: Twenty-five porcine aortas were used to create five models of ATBAD that were connected to a pulsatile flow loop. Models A through C had a patent FL with the following morphologies: model A, single proximal tear; model B, single distal tear; and model C, single proximal and single distal tear. Models D and E had a single proximal and a single distal tear, with partial FL thrombosis. Model D had FL occlusion of the proximal tear, and model D had FL occlusion of the distal tear. True lumen (TL) and FL pressures were measured at 90 to 150 mm Hg. RESULTS: In model A, FL pressures were 6 mm Hg higher than TL pressures (p < 0.01). In model B, FL pressures were 10 mm Hg lower than TL pressures (p ≤ 0.01). In model C, TL and FL pressures were equivalent. In model D, FL pressures were 40 mm Hg lower than TL pressures (p < 0.001). In model E, FL pressures were 10 mm Hg higher than TL pressures (p < 0.01). CONCLUSIONS: In a biologic model of ATBAD, the number, location, and FL thrombosis status determine FL pressure. In the setting of partial FL thrombosis, the FL pressure is reduced with proximal tear occlusion and increased with distal tear occlusion. Reduced FL pressure is related to retrograde flow.

Pre-clinical Experience with a Multi-Chordal Patch for Mitral Valve Repair.

Surgical repair of flail mitral valve leaflets with neochordoplasty has good outcomes, but implementing it in anterior and bi-leaflet leaflet repair is challenging. Placing and sizing individual neochordae is time consuming and error prone, with persistent localized flail if performed incorrectly. In this study, we report our pre-clinical experience with a novel multi-chordal patch for mitral valve repair. The device was designed based on human cadaver hearts, and laser cut from expanded polytetrafluoroethylene. The prototypes were tested in: (stage 1) ex vivo hearts with leaflet flail (N = 6), (stage 2) acute swine induced with flail (N = 6), and (stage 3) two chronic swine survived to 23 and 120 days (N = 2). A2 and P2 prolapse were successfully repaired with coaptation length restored to 8.1 ± 2.2mm after posterior repair and to 10.2 ± 1.3mm after anterior repair in ex vivo hearts. In vivo, trace regurgitation was seen after repair with excellent patch durability, healing, and endothelialization at euthanasia. A new device for easier mitral repair is reported, with good early pre-clinical outcomes.

Temporal changes in interpapillary muscle dynamics as an active indicator of mitral valve and left ventricular interaction in ischemic mitral regurgitation.

BACKGROUND: Regional subpapillary myocardial hypokinesis may impair lateral reduction in the interpapillary muscle distance (IPMD) from diastole to systole, and adversely affect mitral valve geometry and tethering. OBJECTIVES: The goal of this study was to investigate the impact of impaired lateral shortening in the interpapillary muscle distance on mitral valve geometry and function in ischemic heart disease. METHODS: To quantify ventricular size/shape, regional myocardial contraction, lateral shortening of the IPMD, mitral valve geometry, and severity of mitral regurgitation, 67 patients with ischemic heart disease underwent cardiac magnetic resonance imaging, and a correlation analysis of measured parameters was performed. The impact of reduced IPMD shortening on mitral valve (dys)function was confirmed in swine and in a physiological computational mitral valve model. RESULTS: Lateral shortening of the IPMD from diastole to systole was severely reduced in patients with moderate/severe ischemic mitral regurgitation (9.6 ± 2.8 mm), but preserved in mild IMR (11.5 ± 3.4 mm). Left ventricular size and ejection fraction did not differ between the groups. In swine with subpapillary infarction and impaired IPMD, mitral regurgitation was evident within 1 week, compared to those pigs with a nonpapillary infarction and preserved IPMD. In the controlled computational valve model, IPMD had the maximal impact on regurgitation, and was exacerbated with additional annular dilation. CONCLUSIONS: By using cardiac magnetic resonance imaging in humans, we demonstrated that it is the impairment of lateral shortening between the papillary muscles, and not passive ventricular size, that governs the severity of mitral regurgitation. Loss of lateral shortening of IPMD tethers the leaflet edges and impairs their systolic closure, resulting in mitral regurgitation, even in small ventricles. Understanding the lateral dynamics of ventricular-valve interactions could aid the development of new repair techniques for ischemic mitral regurgitation.