Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model.

RATIONALE: Tissue engineering approaches may improve survival and functional benefits from human embryonic stem cell-derived cardiomyocyte transplantation, thereby potentially preventing dilative remodeling and progression to heart failure. OBJECTIVE: Assessment of transport stability, long-term survival, structural organization, functional benefits, and teratoma risk of engineered heart muscle (EHM) in a chronic myocardial infarction model. METHODS AND RESULTS: We constructed EHMs from human embryonic stem cell-derived cardiomyocytes and released them for transatlantic shipping following predefined quality control criteria. Two days of shipment did not lead to adverse effects on cell viability or contractile performance of EHMs (n=3, P=0.83, P=0.87). One month after ischemia/reperfusion injury, EHMs were implanted onto immunocompromised rat hearts to simulate chronic ischemia. Bioluminescence imaging showed stable engraftment with no significant cell loss between week 2 and 12 (n=6, P=0.67), preserving ≤25% of the transplanted cells. Despite high engraftment rates and attenuated disease progression (change in ejection fraction for EHMs, -6.7±1.4% versus control, -10.9±1.5%; n>12; P=0.05), we observed no difference between EHMs containing viable and nonviable human cardiomyocytes in this chronic xenotransplantation model (n>12; P=0.41). Grafted cardiomyocytes showed enhanced sarcomere alignment and increased connexin 43 expression at 220 days after transplantation. No teratomas or tumors were found in any of the animals (n=14) used for long-term monitoring. CONCLUSIONS: EHM transplantation led to high engraftment rates, long-term survival, and progressive maturation of human cardiomyocytes. However, cell engraftment was not correlated with functional improvements in this chronic myocardial infarction model. Most importantly, the safety of this approach was demonstrated by the lack of tumor or teratoma formation.

Surgical technique: papillary muscle sling for functional mitral regurgitation during minimally invasive valve surgery.

In patients with functional mitral regurgitation, the placement of a sling encircling both papillary muscles in conjunction with mitral annuloplasty appears to be a rational approach for surgical correction, because it addresses both the mitral valve and the deformities of the subvalvular mitral apparatus. Reports in the literature that describe the utilization of this technique are few, and mainly involve a median sternotomy approach. The purpose of this communication is to describe the technical details of performing this procedure via a minimally invasive approach.

Effects of targeted papillary muscle relocation on mitral leaflet tenting and coaptation.

BACKGROUND: Ischemic mitral valve (MV) repair for patients with severe left ventricular dilation remains challenging. The objective of this study was to investigate the efficacy of papillary muscle (PM) relocation to restore physiologic MV function. METHODS: Fresh ovine MVs (n = 6) were studied in a left-heart simulator under physiologic hemodynamics. Ischemic MV disease was simulated by annular dilation and PM displacement. Initial valvular repair was performed with mitral annuloplasty; further PM displacement simulated progressive left ventricular dilation. Basal PM repositioning (Kron procedure), performed to alleviate leaflet tethering, consisted of relocating (1) both PMs toward the commissures; (2) both PMs toward the trigones; (3) the posteromedial PM toward the ipsilateral commissure; and (4) the posteromedial PM toward the ipsilateral trigone. Coaptation length and tenting area were measured using three-dimensional echocardiography as surrogates of MV function. RESULTS: Papillary muscle relocation as an adjunct to mitral annuloplasty statistically improved coaptation length and tenting area compared with the disease condition. No statistical differences in coaptation length and tenting area were observed between final repaired conditions and control conditions. No statistical differences were observed between commissural and trigonal repairs at any incremental repair step. Coaptation length and tenting area were plotted against PM distance; the data were fit to linear regressions. CONCLUSIONS: In a realistic in vitro model of ischemic left ventricular dilation, apical-basal PM relocation, as an adjunct procedure to mitral annuloplasty, restored optimal MV closure. Trigonal or commissural traction suture location did not significantly affect the degree of restored coaptation. Linear relationships between PM positions and leaflet variables were established, which could be used to inform surgical repairs.

Papillary muscle sling placement for functional mitral regurgitation during minimally invasive valve surgery.

Herein, we report a case of a 39-year-old woman with an 18-month history of peripartum cardiomyopathy. Transthoracic echocardiography revealed severe functional mitral regurgitation and a left ventricular ejection fraction of 20%. Despite optimal medical therapy, she was in New York Heart Association heart failure class IV, with dyspnea on minimal exertion. The patient underwent minimally invasive mitral valve repair with placement of a papillary muscle sling, which improved her symptoms.

Variations in the papillary muscles of the normal mitral valve and their surgical relevance.

A mid-mitral plane passing through the middle of the aortic and mural leaflets divides the chordopapillary support of the mitral valve into anterolateral and posteromedial halves. The papillary muscles of the mitral valve were studied in 100 human autopsy hearts collected at random. The anterolateral papillary support had 1 belly in 67 hearts, 2 in 27, 3 in 4, 4 in 1, and 5 in 1 heart. Likewise, the posteromedial papillary support had 1 muscle belly in 50 hearts, 2 in 36, 3 in 11, and 4 in 3. The single papillary muscles were conical, mammillated, flat topped, grooved, stepped, wavy, arched, sloped or saucerized. When there were two bellies they presented a two tiered, interlinked, parallel, arched, V, Y, or H configuration. Three papillary muscles formed a parallel, interlinked or arched arrangement; or two bellies were interlinked or formed a two tiered arrangement with the third belly separate. When four or five bellies existed, they were parallel or interlinked. In the anterolateral and posteromedial group, the papillary muscle bellies were mostly intraluminal in 14% and 11%, mostly intraluminal with the tip anchored in 19% and 28%, equally sessile and intraluminal in 54.5% and 41.5%, mostly sessile in 12.5% and 19.5%, respectively. In the anterolateral group 19% of papillary muscle bellies arose from the upper third of the ventricle, 79.5% from middle third, and 1.5% from lower third. The corresponding figures for posteromedial group are 6%, 92.5%, and 1.5%, respectively. Four to 22 chordae originated from the anterolateral papillary group, ending in 14 to 72 chordal insertions into the corresponding half of the valve. Likewise, 2 to 18 chordae arose from the posteromedial papillary group ended in 12 to 80 leaflet insertions. The chordae in each group are best considered in toto as a fan. The configuration of the fan is unique in each heart. Imaging techniques need to be refined to outline these variations more precisely. The relevance of chordopapillary variations in rheumatic heart disease, reparative procedures, papillary muscle dysfunction, mitral valve prolapse, mitral valve replacement, and use of mitral valve homograft for mitral/tricuspid replacement is discussed.