scholarly journals Ex Vivo Model of Functional Mitral Regurgitation Using Deer Hearts

Author(s):  
Michal Jaworek ◽  
Andrea Mangini ◽  
Edoardo Maroncelli ◽  
Federico Lucherini ◽  
Rubina Rosa ◽  
...  

Abstract Transcatheter therapies are emerging for functional mitral regurgitation (FMR) treatment, however there is lack of pathological models for their preclinical assessment. We investigated the applicability of deer hearts for this purpose. 8 whole deer hearts were housed in a pulsatile flow bench. At baseline, all mitral valves featured normal coaptation. The pathological state was induced by 60-minutes intraventricular constant pressurization. It caused mitral annulus dilation (antero-posterior diameter increase from 31.8 ± 5.6 mm to 39.5 ± 4.9 mm, p = 0.001), leaflets tethering (maximal tenting height increase from 7.3 ± 2.5 mm to 12.7 ± 3.4 mm, p < 0.001) and left ventricular diameter increase (from 67.8 ± 7.5 mm to 79.4 ± 6.5 mm, p = 0.004). These geometrical reconfigurations led to restricted mitral valve leaflets motion and leaflet coaptation loss. Preliminary feasibility assessment of two FMR treatments was performed in the developed model. Deer hearts showed ability to dilate under constant pressurization and have potential to be used for realistic preclinical research of novel FMR therapies.

ASAIO Journal ◽  
2020 ◽  
Vol 66 (9) ◽  
pp. 1016-1024 ◽  
Author(s):  
Elorm J. Agra ◽  
Kirthana Sreerangathama Suresh ◽  
Qi He ◽  
Daisuke Onohara ◽  
Robert A. Guyton ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Samantha Zhan Moodie ◽  
Kirthana Sreerangathama Suresh ◽  
Dongyang Xu ◽  
Muralidhar Padala

Introduction: Undersizing annuloplasty (UA), which is the current standard to correct functional mitral regurgitation (FMR) is effective, but the resulting unphysiological systolic geometry causes FMR recurrence. On the other hand, papillary muscle approximation (PMA), a sub-annular technique, reduces inter-papillary separation and tethering forces, mobilizing the leaflets. Objective: To investigate the effect of PMA on mitral valve tethering forces and systolic coaptation geometry, compared to UA. Methods: A left heart model with pig mitral valves was used to create a tethered mitral valve geometry and to perform surgical repairs ( Fig. A ). Mitral valve geometry, and marginal and strut chordal forces acting on both leaflets were measured. Eight individual pig valves (n=8) were studied, with hemodynamic and mechanics data acquired at normal geometry (BASELINE) ( Fig. B) , after tethering (FMR) ( Fig. C) , undersizing annuloplasty (UA) to size 34 (Edwards Lifesciences Physio ring) ( Fig. D) , papillary muscle approximation (PMA), and combination (PMA+UA). Results: Tenting height, which increased after FMR, was least with PMA (0.46 cm± 0.21) and PMA+UA (0.50± 0.16) but remained significantly high with UA (0.73±0.21, p=0.03) ( Fig. E ). Excursion angles of anterior and posterior leaflets were restored close to baseline values after PMA and PMA+UA but remained significantly tethered after UA ( Fig. F & G ). Tethering of the valve increased the strut and marginal chordae forces from 0.47 and 0.14 N to 0.89 and 0.21 N, an increase of 89% and 50% respectively. PMA reduced the forces by 47% and 34%, and PMA+UA reducing it by 43% and 34%to 0.51 while UA only reduced it by 15% and 20% ( Fig. H & I ). Conclusion: PMA significantly reduced the tethering forces on both marginal and strut chordae of both leaflets. Decrease in tethering forces restored the physiologically favorable valve geometry enabling better leaflet mobility and coaptation compared to UA.


Author(s):  
Chetan Pasrija ◽  
Rachael Quinn ◽  
Mehrdad Ghoreishi ◽  
Thomas Eperjesi ◽  
Eric Lai ◽  
...  

Objective Durability of mitral valve (MV) repair for functional mitral regurgitation (FMR) remains suboptimal. We sought to create a highly reproducible, quantitative ex vivo model of FMR that functions as a platform to test novel repair techniques. Methods Fresh swine hearts ( n = 10) were pressurized with air to a left ventricular pressure of 120 mmHg. The left atrium was excised and the altered geometry of FMR was created by radially dilating the annulus and displacing the papillary muscle tips apically and radially in a calibrated fashion. This was continued in a graduated fashion until coaptation was exhausted. Imaging of the MV was performed with a 3-dimensional (3D) structured-light scanner, which records 3D structure, texture, and color. The model was validated using transesophageal echocardiography in patients with normal MVs and severe FMR. Results Compared to controls, the anteroposterior diameter in the FMR state increased 32% and the annular area increased 35% ( P < 0.001). While the anterior annular circumference remained fixed, the posterior circumference increased by 20% ( P = 0.026). The annulus became more planar and the tenting height increased 56% (9 to 14 mm, P < 0.001). The median coaptation depth significantly decreased (anterior leaflet: 5 vs 2 mm; posterior leaflet: 7 vs 3 mm, P < 0.001). The ex vivo normal and FMR models had similar characteristics as clinical controls and patients with severe FMR. Conclusions This novel quantitative ex vivo model provides a simple, reproducible, and inexpensive benchtop representation of FMR that mimics the systolic valvular changes of patients with FMR.


2013 ◽  
Vol 16 (6) ◽  
pp. 329
Author(s):  
Eric Monnet ◽  
Kristal Pouching

<p><b>Objective:</b> Functional mitral regurgitation (FMR) is a common sequelae of myocardial ischemic disease. It results from annular dilation and outward rotation of the posterior papillary muscle. Different surgical techniques are under investigation for the treatment of FMR. However, an ex vivo model of FMR would be valuable to develop and compare the effect of techniques on the geometry of the left ventricle and the correction of FMR.</p><p><b>Methods:</b> FMR was induced in explanted ovine hearts (n = 12) by manual dilation of the mitral annulus or by posterior papillary muscle repositioning with a patch. Left ventricular dimensions were measured. Mitral regurgitant volume (MRV) was measured in a continuous flow system.</p><p><b>Results:</b> Annular dilation significantly increased MRV from 93.0 � 110.4 to 472.2 � 211.8 mL/min (<i>P</i> = 0.031), and the patch increased it from 37.8 � 55.2 to 365 � 189.6 mL/min (<i>P</i> = 0.031), with no significant differences between the 2 groups. When both techniques were applied, MRV significantly increased to 1383.5 � 567.0 mL/min (<i>P</i> = 0.0005). The left ventricular sphericity index decreased from 3.25 � 0.7 to 2.34 � 0.6 (<i>P</i> = 0.0025) after application of the patch. The posterior papillary muscle was displaced after patch placement, following an outward rotation.</p><p><b>Conclusion:</b> This ex vivo model reproduces annular dilation and outward rotation of the posterior papillary muscle, which are both present during FMR after ischemic myocardial disease. This model could be used to evaluate and compare interventions to treat FMR.</p>


Author(s):  
Bo Gao ◽  
Zhaoming He

Functional mitral regurgitation, which occurs as a consequence of regional of global left ventricular or global left ventricular dysfunction despite structurally normal mitral valve (MV), is a common complication in patients with ischemic or non-ischemic cardiomyopathies [1].


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kitamura ◽  
T Schmidt ◽  
D Schewel ◽  
H Alessandrini ◽  
K.-H Kuck ◽  
...  

Abstract Background In patients with functional mitral regurgitation (FMR), deformation of the mitral valve (MV) apparatus leads to deteriorating coaptation of both leaflets. The MV geometry is essential to predict procedural success of using the MitraClip™ for FMR patients. Persistent such mitral regurgitation (MR) and post-procedural mitral stenosis (MS) are parameters for an increasing mortality rate after MitraClip implantation. The anterior-to-posterior mitral annulus diameter (MAD) is simple to evaluate with a high reproducibility rate. However, the predictive effect has not been determined to date. Purpose We evaluated the predictive effect of baseline anterior-to-posterior MAD on persistent MV dysfunctions after MitraClip™ implantation. Methods We investigated the prevalence of procedural failure (MR at discharge > grade 2+) and post-procedural MS (mean transmitral gradient (mTMG) at discharge ≥6 mmHg) in a patient cohort with FMR (n=190), who underwent MitraClip™ implantation. We measured the MV apparatus geometry on mid-systole using transoesophageal echocardiography before the index procedure. The MAD was stratified by interquartile ranges (IQR) in the comparison. (≤34 mm, 35 to 37 mm, 38 to 40 mm, and ≥41 mm, respectively) Results The mean age was 75±9 years, and 63 patients (33%) were female. The mean left ventricular ejection fraction was 34±14%. Moderate-to-severe (3+) or severe MR (4+) were documented in all patients before the procedure. Transthoracic echocardiography at discharge revealed residual MR (>2+) in 10 patients (5%) and post-procedural MS in 13 patients (7%), in which one patient presented with both residual MR and MS. After stratification by the IQRs of MAD, there were significant differences in body weight (p<0.001), height (p<0.001), and body surface area (p<0.001), but no significant differences in the other baseline characteristics. Notably, significant differences in the prevalence of procedural failure (p=0.004) and post-procedural MS (p=0.022) were observed among the groups. (Figure) Specifically, in the cohort with the 4th IQR (MAD ≥41 mm, n=44), procedural failure was observed in 7 patients (16%), although the prevalence was only 2% in the other IQR groups. Moreover, the cohorts with the 1st and 2nd IQR presented with higher prevalence of post-procedural MS (6 of 46 patients (13%) in the 1st IQR group, and 6 of 51 (12%) in the 2nd IQR group) than those with the 3rd and 4th IQRs. (1 of 49 patients (2%) in the 3rd IQR, and none of 44 patients in the 4th IQR) Figure 1 Conclusion In this analysis we showed that the mitral annulus size affected MV dysfunction after MitraClip™. Anterior-to-posterior MAD was useful to predict the procedural result. For FMR candidates with dilated mitral annulus larger than 40 mm, new-generation MitraClip-XTR™ system or other therapeutic concept such as annuloplasty may be reasonable to obtain satisfactory MV function.


2018 ◽  
Vol 21 (4) ◽  
pp. E275-E280
Author(s):  
Krishaporn Kradangnga ◽  
Eric Monnet

Background: Surgical method of choice for functional mitral regurgitation (FMR) is debatable, since recurrence of FMR post-annuloplasty has been reported in a significant number of cases. Developing a pulsatile FMR heart model by left ventricular dilatation can be a favorable option for usage in the primary stages of developing new surgical techniques that adjunctively targets the posterior papillary muscle (PPM) geometry.Methods: PPM of ex vivo ovine hearts (N = 22) was displaced by three different sizes of patches to induce left ventricular dilatation and FMR. Mitral regurgitation (MR) flow, left ventricular and annular geometry were measured from the dynamic pulsatile flow system before and after patch placement.Results: Outward displacement of PPM was significantly increased in all patch sizes compared to baseline (P = .016, P = .031, and P = .008 from small to large patch, respectively). Left ventricular volume (LVV) significantly increased from 18.53 (15.01-26.03) mL at baseline to 27.5 (19.45-42.46) mL after large patch placement (P = .031). However, the small and medium patch groups did not show significant changes in the LVV after patch placement. MR significantly increased 554 (185-1,919.3) mL/min after applying the large patch compared to baseline (P = .016). There were no significant changes from baseline in MR flow after applying the small and medium patch. Application of the large patch produced the highest proportion of FMR heart models (87.5%, P = .031).Conclusion: The large patch ex vivo pulsatile heart model demonstrated outward displacement of the PPM and significantly produced MR flow. This ex vivo pulsatile heart model can be used to facilitate surgical techniques that targets the PPM displacement in FMR patients.


Circulation ◽  
1999 ◽  
Vol 100 (suppl_2) ◽  
Author(s):  
G. Randall Green ◽  
Paul Dagum ◽  
Julie R. Glasson ◽  
George T. Daughters ◽  
Ann F. Bolger ◽  
...  

Background —Asymmetrical mitral annular (MA) dilatation and papillary muscle dislocation are implicated in the pathogenesis of functional mitral regurgitation (MR). Methods and Results —To determine the mechanism by which annular and papillary muscle geometric alterations result in MR, we implanted radiopaque markers in the left ventricle, mitral annulus, anterior and posterior mitral leaflets, and papillary muscle tips and bases in 2 groups of sheep. One group served as controls (CTL, n=7); an experimental group (EXP, n=9) underwent topical phenol application to obliterate anterior annular and leaflet muscle (confirmed histologically ex vivo). After 1 week of recovery, markers were imaged with biplane videofluoroscopy, and hemodynamic data were recorded. MA area (computed from 3-dimensional marker coordinates) was 11% to 13% larger in the EXP group than in the CTL group ( P <0.05 by ANOVA). This area increase resulted exclusively from intercommissural axis increase except in 1 heart with large (>1 cm) increases in both the intercommissural and septolateral annular axes. The anterior papillary muscle tip in EXP was displaced from CTL by 2.9±0.23 mm toward the anterolateral left ventricle and 2.5±0.12 mm toward the mitral annulus at end systole; the posterior papillary muscle geometry was unchanged. Transthoracic echocardiography revealed MR only in the heart exhibiting biaxial annular enlargement. Conclusions —MA dilatation in the intercommissural dimension with anterior papillary muscle tip displacement toward the annulus is insufficient to produce MR in sheep. Functional MR may require MA dilatation in the septolateral axis, as observed with proximal circumflex coronary occlusion.


2009 ◽  
Vol 5 (1) ◽  
pp. 67
Author(s):  
Lutz Buellesfeld ◽  
Lazar Mandinov ◽  
Eberhard Grube ◽  
◽  
◽  
...  

Functional mitral regurgitation affects a substantial proportion of patients with congestive heart failure due to myocardial infarction or dilated cardiomyopathy. Functional mitral regurgitation greatly increases morbidity and mortality. Surgical annuloplasty is the standard of care for symptomatic patients with moderate or severe functional mitral regurgitation; however, a large number of patients are refused surgery. Several percutaneous approaches have been developed to address the need for less invasive treatment of mitral annulus dilatation. Devices using coronary sinus to cinch the mitral annulus are relatively easy to use; however, a number of factors may limit their clinical application, such as suboptimal anatomical relationship between the coronary sinus and mitral annulus, risk of coronary artery compression, large variability in the coronary venous anatomy and conflict with other therapies such as ablation or cardiac resynchronisation. Direct mitral annuloplasty is anticipated to be more effective than the coronary sinus approaches; however, it has yet to prove its safety and efficacy in carefully designed clinical trials. The best candidates and the best timing for each percutaneous mitral annuloplasty therapy, whether direct or indirect, have yet to be identified.


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