Short-Term Outcomes, Functional Status, and Risk Factors for Requiring Extracorporeal Life Support After Norwood Operation: A Single-Center Retrospective Study.

Patients requiring extracorporeal life support (ECLS) post-Norwood operation constitute an extremely high-risk group. We retrospectively described short-term outcomes, functional status, and assessed risk factors for requiring ECLS post-Norwood operation between January 2010 and December 2020 in a high-volume center. During the study period, 269 patients underwent a Norwood procedure of which 65 (24%) required ECLS. Of the 65 patients, 27 (41.5%) survived to hospital discharge. Mean functional status scale (FSS) score at discharge increased from 6.0 on admission to 8.48 (p < 0.0001). This change was primary in feeding (p < 0.0001) and respiratory domains (p = 0.017). Seven survivors (26%) developed new morbidity, and two (7%) developed unfavorable functional outcomes. In the regression analysis, we showed that patients with moderate-severe univentricular dysfunction on pre-Norwood transthoracic echocardiogram (odds ratio [OR] = 6.97), modified Blalock Taussig Thomas (m-BTT) shunt as source of pulmonary blood flow (OR = 2.65), moderate-severe atrioventricular valve regurgitation on transesophageal echocardiogram (OR = 8.50), longer cardiopulmonary bypass time (OR = 1.16), longer circulatory arrest time (OR = 1.20), and delayed sternal closure (OR = 3.86), had higher odds of requiring ECLS (p < 0.05). Careful identification of these risk factors is imperative to improve the care of this high-risk cohort and improve overall outcomes.

In vivo efficacy of a polymer layered decellularized matrix composite as a cell honing cardiovascular tissue substitute.

Cardiovascular surgery involves reconstruction of tissues that are under cyclical mechanical loading, and in constant contact with pulsatile blood flow. Durable biomaterials for such tissue reconstruction are scarce, as they need to be mechanically strong, hemocompatible, and resist structural deterioration from calcification. While homografts are ideal, they are scarce; xenografts are immunogenic and rendered inactive from glutaraldehyde fixation, causing them to calficy and structurally deteriorate over time; decellularized xenografts are devoid of cells, mechanically weak; and synthetic polymeric scaffolds are thrombogenic or too dense to enable host cell infiltration. In this work, we report the in vivo feasibility of a new polymer-decellularized matrix composite material (decellularized bovine pericardium-polycaprolactone: chitosan) fabricated by electrospinning, which is designed to be mechanically strong and achieve programmed host cell honing to integrate into the host. In a rodent and sheep model, this new material was found to be hemocompatible, and enabled host cell infiltration into the polymer and the decellularized matrix core underlying the polymer. Presence of M2 macrophages and several vascular cell types, with matrix remodeling in the vicinity of the cells was observed in the explanted tissues. In summary, the proposed composite material is a novel approach to create in-situ host integrating tissue substitutes, with better non-thrombogenicity, reduced infections and endocarditis, and potentially the ability to grow with the patient and remodeling into a native tissue structure.

A Biohybrid Material With Extracellular Matrix Core and Polymeric Coating as a Cell Honing Cardiovascular Tissue Substitute.

Objective: To investigate the feasibility of a hybrid material in which decellularized pericardial extracellular matrix is functionalized with polymeric nanofibers, for use as a cardiovascular tissue substitute. Background: A cardiovascular tissue substitute, which is gradually resorbed and is replaced by host's native tissue, has several advantages. Especially in children and young adults, a resorbable material can be useful in accommodating growth, but also enable rapid endothelialization that is necessary to avoid thrombotic complications. In this study, we report a hybrid material, wherein decellularized pericardial matrix is functionalized with a layer of polymeric nanofibers, to achieve the mechanical strength for implantation in the cardiovascular system, but also have enhanced cell honing capacity. Methods: Pericardial sacs were decellularized with sodium deoxycholate, and polycaprolactone-chitosan fibers were electrospun onto the matrix. Tissue-polymer interaction was evaluated using spectroscopic methods, and the mechanical properties of the individual components and the hybrid material were quantified. In-vitro blood flow loop studies were conducted to assess hemocompatibility and cell culture methods were used to assess biocompatibility. Results: Encapsulation of the decellularized matrix with 70 µm thick matrix of polycaprolactone-chitosan nanofibers, was feasible and reproducible. Spectroscopy of the cross-section depicted new amide bond formation and C-O-C stretch at the interface. An average peel strength of 56.13 ± 11.87 mN/mm2 was measured, that is sufficient to withstand a high shear of 15 dynes/cm2 without delamination. Mechanical strength and extensibility ratio of the decellularized matrix alone were 18,000 ± 4,200 KPa and 0.18 ± 0.03% whereas that of the hybrid was higher at 20,000 ± 6,600 KPa and 0.35 ± 0.20%. Anisotropy index and stiffness of the biohybrid were increased as well. Neither thrombus formation, nor platelet adhesion or hemolysis was measured in the in-vitro blood flow loop studies. Cellular adhesion and survival were adequate in the material. Conclusion: Encapsulating a decellularized matrix with a polymeric nanofiber coating, has favorable attributes for use as a cardiovascular tissue substitute.

Hemodynamic outcomes after undersizing ring annuloplasty and focal suture annuloplasty for surgical repair of functional tricuspid regurgitation.

OBJECTIVE: Surgical annuloplasty for functional tricuspid regurgitation (FTR) is on the rise and can be performed in several ways with varied outcomes. In this study, we sought to compare the hemodynamic outcomes of tricuspid annuloplasty performed with a commercially available annuloplasty ring (tricuspid valve annuloplasty [TVA]) compared with focal suture annuloplasty (Hetzer) in an experimental FTR model. METHODS: An ex vivo FTR model was developed by inducing right ventricular dilatation by acute afterload elevation, causing severe tricuspid valve tethering and annular dilatation, leading to regurgitation. Ten porcine hearts in which FTR was induced underwent TVA with a 26-mm Edwards MC3 ring and Hetzer annuloplasty with a pledgeted suture cinching the anteroposterior and septal annulus. FTR was measured before after each repair, and tenting geometry, valve kinematics, and subvalvular geometry were measured with echocardiography. RESULTS: At baseline, none of the hearts had FTR, but upon afterload elevation an FTR volume of 17.7 ± 9.2 mL (26.38 ± 17.47% regurgitant fraction) was measured (P < .0001). TVA reduced regurgitation by 50% and Hetzer annuloplasty by 56% , respectively, but both left persistent FTR. Anteroseptal tenting area was 279.0 ± 158.9 mm2 before repair and decreased significantly to 147.2 ± 134.8 mm2 (P = .0195) with Hetzer but not with TVA. Posteroseptal tenting area was 425.1 ± 169.2 mm2 before repair and was significantly reduced by both techniques (TVA: 200.3 ± 102.9 mm2 [P = .0012]; Hetzer: 237.6 ± 127.6 mm2 [P = .0270]). CONCLUSIONS: Tricuspid annuloplasty with a ring or a focal suture can reduce FTR but not eliminate it. Annular approaches did not relieve tricuspid valve tethering and reduced leaflet mobility persisted. Either subannular repairs or judicious use of valve replacement may be necessary.

Effect of early versus late onset mitral regurgitation on left ventricular remodeling in ischemic cardiomyopathy in an animal model.

BACKGROUND: Patients who survive a myocardial infarction have progressive cardiac dysfunction and ventricular remodeling. Mitral regurgitation is often diagnosed in these patients, and is a risk factor that portends poor prognosis. Whether such postinfarction mitral regurgitation magnifies adverse left ventricular remodeling is unclear, which was studied in an animal model. METHODS: Forty-one adult rats were induced with myocardial infarction using left coronary artery ligation and assigned to 3 groups: group 1, myocardial infarction only; group 2, myocardial infarction with severe mitral regurgitation introduced after 4 weeks; and group 3, myocardial infarction with severe mitral regurgitation introduced after 10 weeks. Valve regurgitation was introduced by advancing a transapical ultrasound-guided needle into the mitral valve anterior leaflet. Animals were survived to 20 weeks from the index procedure, with biweekly cardiac ultrasound, and invasive hemodynamics and histology at termination. RESULTS: At 20 weeks, end diastolic volume was largest in the groups with mitral regurgitation, compared with the group without the valve lesion (group 1, 760.9 ± 124.6 µL; group 2, 958.0 ± 115.1 µL; group 3, 968.3 ± 214.9 µL). Similarly, end systolic volume was larger in groups with regurgitation (group 1, 431.2 ± 152.6 µL; group 2, 533.2 ± 130.8 µL; group 3, 533.1 ± 177.5 µL). In the infarction-only group, left ventricular remodeling was maximal until 6 weeks and plateaued thereafter. In groups with mitral regurgitation, left ventricular remodeling was significantly elevated at the onset of regurgitation and persisted. CONCLUSIONS: Mitral regurgitation is a potent driver of adverse cardiac remodeling after a myocardial infarction, irrespective of the timing of its onset.

Hemodynamic and transcriptomic studies suggest early left ventricular dysfunction in a preclinical model of severe mitral regurgitation.

OBJECTIVE: Primary mitral regurgitation is a valvular lesion in which the left ventricular ejection fraction remains preserved for long periods, delaying a clinical trigger for mitral valve intervention. In this study, we sought to investigate whether adverse left ventricular remodeling occurs before a significant fall in ejection fraction and characterize these changes. METHODS: Sixty-five rats were induced with severe mitral regurgitation by puncturing the mitral valve leaflet with a 23-G needle using ultrasound guidance. Rats underwent longitudinal cardiac echocardiography at biweekly intervals and hearts explanted at 2 weeks (n = 15), 10 weeks (n = 15), 20 weeks (n = 15), and 40 weeks (n = 15). Sixty age- and weight-matched healthy rats were used as controls. Unbiased RNA-sequencing was performed at each terminal point. RESULTS: Regurgitant fraction was 40.99 ± 9.40%, with pulmonary flow reversal in the experimental group, and none in the control group. Significant fall in ejection fraction occurred at 14 weeks after mitral regurgitation induction. However, before 14 weeks, end-diastolic volume increased by 93.69 ± 52.38% (P < .0001 compared with baseline), end-systolic volume increased by 118.33 ± 47.54% (P < .0001 compared with baseline), and several load-independent pump function indices were reduced. Transcriptomic data at 2 and 10 weeks before fall in ejection fraction indicated up-regulation of myocyte remodeling and oxidative stress pathways, whereas those at 20 and 40 weeks indicated extracellular matrix remodeling. CONCLUSIONS: In this rodent model of mitral regurgitation, left ventricular ejection fraction was preserved for a long duration, yet rapid and severe left ventricular dilatation, and biological remodeling occurred before a clinically significant fall in ejection fraction.