Electromechanical coupling between skeletal and cardiac muscle. Implications for infarct repair

Skeletal myoblasts form grafts of mature muscle in injured hearts, and these grafts contract when exogenously stimulated. It is not known, however, whether cardiac muscle can form electromechanical junctions with skeletal muscle and induce its synchronous contraction. Here, we report that undifferentiated rat skeletal myoblasts expressed N-cadherin and connexin43, major adhesion and gap junction proteins of the intercalated disk, yet both proteins were markedly downregulated after differentiation into myo-tubes. Similarly, differentiated skeletal muscle grafts in injured hearts had no detectable N-cadherin or connexin43; hence, electromechanical coupling did not occur after in vivo grafting. In contrast, when neonatal or adult cardiomyocytes were cocultured with skeletal muscle, approximately 10% of the skeletal myotubes contracted in synchrony with adjacent cardiomyocytes. Isoproterenol increased myotube contraction rates by 25% in coculture without affecting myotubes in monoculture, indicating the cardiomyocytes were the pacemakers. The gap junction inhibitor heptanol aborted myotube contractions but left spontaneous contractions of individual cardiomyocytes intact, suggesting myotubes were activated via gap junctions. Confocal microscopy revealed the expression of cadherin and connexin43 at junctions between myotubes and neonatal or adult cardiomyocytes in vitro. After microinjection, myotubes transferred dye to neonatal cardiomyocytes via gap junctions. Calcium imaging revealed synchronous calcium transients in cardiomyocytes and myotubes. Thus, cardiomyocytes can form electromechanical junctions with some skeletal myotubes in coculture and induce their synchronous contraction via gap junctions. Although the mechanism remains to be determined, if similar junctions could be induced in vivo, they might be sufficient to make skeletal muscle grafts beat synchronously with host myocardium.     

Multidisciplinary decision-making in mitral valve disease: the mitral valve heart team

Background

Although decision-making using the heart-team approach is apparently intuitive and has a class I recommendation in most recent guidelines, supportive data is still lacking. The current study aims to demonstrate the individualised clinical pathway for mitral valve disease patients and to evaluate the outcome of all patients referred to the dedicated mitral valve heart team.

Methods

All patients who were evaluated for mitral valve pathology with or without concomitant cardiac disease between 1 January 2016 and 31 December 2016 were prospectively followed and included. Patients were evaluated, and a treatment strategy was determined by the dedicated mitral valve heart team.

Results

One hundred and fifty-eight patients were included; 67 patients were treated surgically (isolated and concomitant surgery), 20 by transcatheter interventions and 71 conservatively. Surgically treated patients had a higher 30-day mortality rate (4.4%), which decreased when specified to a dedicated surgeon (1.7%) and in primary, elective cases (0%). This was also observed for major adverse events within 30 days. Residual mitral regurgitation >grade 2 was more frequent in the catheter-based intervention group (23.5%) compared to the surgical group (4.8%).

Conclusion

In conclusion, the implementation of a multidisciplinary heart team for mitral valve disease is a valuable approach for the selection of patients for different treatment modalities. Our research group will focus on a future comparative study using historical cohorts to prove the potential superiority of the dedicated multidisciplinary heart-team approach.

     

Mechanics of the mitral valve

Alterations in mitral valve mechanics are classical indicators of valvular heart disease, such as mitral valve prolapse, mitral regurgitation, and mitral stenosis. Computational modeling is a powerful technique to quantify these alterations, to explore mitral valve physiology and pathology, and to classify the impact of novel treatment strategies. The selection of the appropriate constitutive model and the choice of its material parameters are paramount to the success of these models. However, the in vivo parameters values for these models are unknown. Here, we identify the in vivo material parameters for three common hyperelastic models for mitral valve tissue, an isotropic one and two anisotropic ones, using an inverse finite element approach. We demonstrate that the two anisotropic models provide an excellent fit to the in vivo data, with local displacement errors in the sub-millimeter range. In a complementary sensitivity analysis, we show that the identified parameter values are highly sensitive to prestrain, with some parameters varying up to four orders of magnitude. For the coupled anisotropic model, the stiffness varied from 119,021 kPa at 0 % prestrain via 36 kPa at 30 % prestrain to 9 kPa at 60 % prestrain. These results may, at least in part, explain the discrepancy between previously reported ex vivo and in vivo measurements of mitral leaflet stiffness. We believe that our study provides valuable guidelines for modeling mitral valve mechanics, selecting appropriate constitutive models, and choosing physiologically meaningful parameter values. Future studies will be necessary to experimentally and computationally investigate prestrain, to verify its existence, to quantify its magnitude, and to clarify its role in mitral valve mechanics.     

Bioprosthetic mitral valve thrombosis

Netherlands Heart Journal -     

Lambl's excrescences of the mitral valve

A young male patient, just recovered from a recent transient ischaemic attack, was operated on for mitral valve insufficiency due to suspected endocarditis. Multiple wear-and-tear lesions were found at the line of closure of the mitral valve, which appeared to be Lambl''s excrescences. The valve was replaced.     

Papillary fibroelastoma of the mitral valve

We present a case of a 69-year-old woman with a history of stroke five years previously and an abnormal ECG prior to eye surgery. There were no signs of cardiac disease. Echocardiography disclosed a tumour of the papillary muscle. Surgical excision was performed and histological examination confirmed the diagnosis of a papillary fibroelastoma.     

Electromechanical coupling of waves in nerve fibres

The propagation of an action potential (AP) in a nerve fibre is accompanied by mechanical and thermal effects. In this paper, an attempt is made to build up a mathematical model which couples the AP with a possible pressure wave (PW) in the axoplasm and waves in the nerve fibre wall (longitudinal—LW and transverse—TW) made of a lipid bilayer (biomembrane). A system of differential equations includes the governing equations of single waves with coupling forces between them. The single equations are kept as simple as possible in order to carry out the proof of concept. An assumption based on earlier studies is made that the coupling forces depend on changes (the gradient, time derivative) of the voltage. In addition, it is assumed that the transverse displacement of the biomembrane can be calculated from the gradient of the LW in the biomembrane. The computational simulation is focused to determining the influence of possible coupling forces on the emergence of mechanical waves from the AP. As a result, an ensemble of waves (AP, PW, LW, TW) emerges. The further experiments should verify assumptions about coupling forces.     

Comparison of mitral annulus geometry between patients with ischemic and non-ischemic functional mitral regurgitation: implications for transcatheter mitral valve implantation

Background

Transcatheter mitral valve replacement (TMVR) is a new therapeutic option for high surgical risk patients with mitral regurgitation (MR). Mitral valve (MV) geometry quantification is of paramount importance for success of the procedure and transthoracic 3D echocardiography represents a useful screening tool. Accordingly, we sought to asses MV geometry in patients with functional MR (FMR) that would potentially benefit of TMVR, focusing on the comparison of mitral annulus (MA) geometry between patients with ischemic (IMR) and non ischemic mitral regurgitation (nIMR).

Methods

We retrospectively selected 94 patients with severe FMR: 41 (43,6%) with IMR and 53 (56,4%) with nIMR. 3D MA analysis was performed on dedicated transthoracic 3D data sets using a new, commercially-available software package in two moments of the cardiac cycle (early-diastole and mid-systole). We measured MA dimension and geometry parameters, left atrial and left ventricular volumes.

Results

Maximum (MA area 10.7?±?2.5 cm² vs 11.6?±?2.7 cm², p?>?0.05) and the best fit plane MA area (9.9?±?2.3 cm² vs 10.7?±?2.5 cm², p?>?0.05, respectively) were similar between IMR and nIMR. nIMR patients showed larger mid-systolic 3D area (9.8?±?2.3 cm² vs 10.8?±?2.7 cm², p?<?0.05) and perimeter (11.2?±?1.3 cm vs 11.8?±?1.5 cm, p?<?0.05) with longer and larger leaflets, and wider aorto-mitral angle (135?±?10° vs 141?±?11°, p?<?0.05). Conversely, the area of MA at the best fit plane did not differ between IMR and nIMR patients (9?±?1.1 cm² vs 9.9?±?1.5 cm², p?>?0.05).

Conclusions

Patients with ischemic and non-ischemic etiology of FMR have similar maximum dimension, yet systolic differences between the two groups should be taken into account to tailor prosthesis’s selection.

Trial registration

N.A.

     

The relation between collagen fibril kinematics and mechanical properties in the mitral valve anterior leaflet

We have recently demonstrated that the mitral valve anterior leaflet (MVAL) exhibited minimal hysteresis, no strain rate sensitivity, stress relaxation but not creep (Grashow et al., 2006, Ann Biomed Eng., 34(2), pp. 315-325; Grashow et al., 2006, Ann Biomed. Eng., 34(10), pp. 1509-1518). However, the underlying structural basis for this unique quasi-elastic mechanical behavior is presently unknown. As collagen is the major structural component of the MVAL, we investigated the relation between collagen fibril kinematics (rotation and stretch) and tissue-level mechanical properties in the MVAL under biaxial loading using small angle X-ray scattering. A novel device was developed and utilized to perform simultaneous measurements of tissue level forces and strain under a planar biaxial loading state. Collagen fibril D-period strain (epsilonD) and the fibrillar angular distribution were measured under equibiaxial tension, creep, and stress relaxation to a peak tension of 90 N/m. Results indicated that, under equibiaxial tension, collagen fibril straining did not initiate until the end of the nonlinear region of the tissue-level stress-strain curve. At higher tissue tension levels, epsilonD increased linearly with increasing tension. Changes in the angular distribution of the collagen fibrils mainly occurred in the tissue toe region. Using epsilonD, the tangent modulus of collagen fibrils was estimated to be 95.5+/-25.5 MPa, which was approximately 27 times higher than the tissue tensile tangent modulus of 3.58+/-1.83 MPa. In creep tests performed at 90 N/m equibiaxial tension for 60 min, both tissue strain and epsilonD remained constant with no observable changes over the test length. In contrast, in stress relaxation tests performed for 90 min epsilonD was found to rapidly decrease in the first 10 min followed by a slower decay rate for the remainder of the test. Using a single exponential model, the time constant for the reduction in collagen fibril strain was 8.3 min, which was smaller than the tissue-level stress relaxation time constants of 22.0 and 16.9 min in the circumferential and radial directions, respectively. Moreover, there was no change in the fibril angular distribution under both creep and stress relaxation over the test period. Our results suggest that (1) the MVAL collagen fibrils do not exhibit intrinsic viscoelastic behavior, (2) tissue relaxation results from the removal of stress from the fibrils, possibly by a slipping mechanism modulated by noncollagenous components (e.g. proteoglycans), and (3) the lack of creep but the occurrence of stress relaxation suggests a "load-locking" behavior under maintained loading conditions. These unique mechanical characteristics are likely necessary for normal valvular function.     

Fatigue exhaustion of the mitral valve tissue

Biomechanics and Modeling in Mechanobiology - Sudden failure and rupture of the tissue is a rare but serious short-term complication after the mitral valve surgical repair. Excessive cyclic loading...     

Percutaneous mitral valve repair: the necessity to redefine secondary mitral regurgitation

Netherlands Heart Journal - Interest in percutaneous mitral valve repair has increased during recent years. This is mainly driven by the significant number of patients being declined for mitral...     

Exuberant accessory mitral valve tissue with possible true parachute mitral valve: a case report

ABSTRACT: INTRODUCTION: A parachute mitral valve is defined as a unifocal attachment of mitral valve chordae tendineae independent of the number of papillary muscles. Data from the literature suggests that the valve can be distinguished on the basis of morphological features as either a parachute-like asymmetrical mitral valve or a true parachute mitral valve. A parachute-like asymmetrical mitral valve has two papillary muscles; one is elongated and located higher in the left ventricle. A true parachute mitral valve has a single papillary muscle that receives all chordae, as was present in our patient. Patients with parachute mitral valves during childhood have multilevel left-side heart obstructions, with poor outcomes without operative treatment. The finding of a parachute mitral valve in an adult patient is extremely rare, especially as an isolated lesion. In adults, the unifocal attachment of the chordae results in a slightly restricted valve opening and, more frequently, valvular regurgitation. CASE PRESENTATION: A 40-year-old Caucasian female patient was admitted to a primary care physician due to her recent symptoms of heart palpitation and chest discomfort on effort. Transthoracic echocardiography showed chordae tendineae which were elongated and formed an unusual net shape penetrating into left ventricle cavity. The parasternal short axis view of her left ventricle showed a single papillary muscle positioned on one side in the posteromedial commissure receiving all chordae. Her mitral valve orifice was slightly eccentric and the chordae were converting into a single papillary muscle. Mitral regurgitation was present and it was graded as moderate to severe. Her left atrium was enlarged. There were no signs of mitral stenosis or a subvalvular ring. She did not have a bicuspid aortic valve or coarctation of the ascending aorta. The dimensions and systolic function of her left ventricle were normal. Our patient had a normal body habitus, without signs of heart failure. Her functional status was graded as class I according to the New York Heart Association grading. CONCLUSIONS: A recently published review found that, in the last several decades, there have been only nine adult patients with parachute mitral valve disease reported, of which five had the same morphological characteristics as our patient. This case presentation should encourage doctors, especially those involved in echocardiography, to contribute their own experience, knowledge and research in parachute mitral valve disease to enrich statistical and epidemiologic databases and aid clinicians in getting acquainted with this rare disease.     

The serpentine mitral valve and cerebral embolism

Valvular strands, well-delineated filiform masses, attached to cardiac valve edges are associated with cerebral embolism and stroke. Strokes, caused by emboli from valvular strands, tend to occur among younger persons. In this case report a valvular strand, giving a peculiar serpentine appearance to the mitral valve is described. This mitral valvular strand was the only explanation for an episode of cerebral embolism, presenting with a transient right sided hemiparesis. It is proposed that a randomized study involving combined treatment with aspirin and clopidogrel is warranted in young patients with valvular strands, presenting with a first episode of cerebral embolism.