A Unique Collateral Artery Development Program Promotes Neonatal Heart Regeneration.

Collateral arteries are an uncommon vessel subtype that can provide alternate blood flow to preserve tissue following vascular occlusion. Some patients with heart disease develop collateral coronary arteries, and this correlates with increased survival. However, it is not known how these collaterals develop or how to stimulate them. We demonstrate that neonatal mouse hearts use a novel mechanism to build collateral arteries in response to injury. Arterial endothelial cells (ECs) migrated away from arteries along existing capillaries and reassembled into collateral arteries, which we termed "artery reassembly". Artery ECs expressed CXCR4, and following injury, capillary ECs induced its ligand, CXCL12. CXCL12 or CXCR4 deletion impaired collateral artery formation and neonatal heart regeneration. Artery reassembly was nearly absent in adults but was induced by exogenous CXCL12. Thus, understanding neonatal regenerative mechanisms can identify pathways that restore these processes in adults and identify potentially translatable therapeutic strategies for ischemic heart disease.

Comprehensive Ex Vivo Comparison of 5 Clinically Used Conduit Configurations for Valve-Sparing Aortic Root Replacement Using a 3-Dimensional-Printed Heart Simulator.

BACKGROUND: Many graft configurations are clinically used for valve-sparing aortic root replacement, some specifically focused on recapitulating neosinus geometry. However, the specific impact of such neosinuses on valvular and root biomechanics and the potential influence on long-term durability are unknown. METHODS: Using a custom 3-dimenstional-printed heart simulator with porcine aortic roots (n=5), the anticommissural plication, Stanford modification, straight graft (SG), Uni-Graft, and Valsalva graft configurations were tested in series using an incomplete counterbalanced measures design, with the native root as a control, to mitigate ordering effects. Hemodynamic and videometric data were analyzed using linear models with conduit as the fixed effect of interest and valve as a fixed nuisance effect with post hoc pairwise testing using Tukey's correction. RESULTS: Hemodynamics were clinically similar between grafts and control aortic roots. Regurgitant fraction varied between grafts, with SG and Uni-Graft groups having the lowest regurgitant fractions and anticommissural plication having the highest. Root distensibility was significantly lower in SG versus both control roots and all other grafts aside from the Stanford modification (P≤0.01 for each). All grafts except SG had significantly higher cusp opening velocities versus native roots (P<0.01 for each). Relative cusp opening forces were similar between SG, Uni-Graft, and control groups, whereas anticommissural plication, Stanford modification, and Valsalva grafts had significantly higher opening forces versus controls (P<0.01). Cusp closing velocities were similar between native roots and the SG group, and were significantly lower than observed in the other conduits (P≤0.01 for each). Only SG and Uni-Graft groups experienced relative cusp closing forces approaching that of the native root, whereas relative forces were >5-fold higher in the anticommissural plication, Stanford modification, and Valsalva graft groups. CONCLUSIONS: In this ex vivo modeling system, clinically used valve-sparing aortic root replacement conduit configurations have comparable hemodynamics but differ in biomechanical performance, with the straight graft most closely recapitulating native aortic root biomechanics.

Untwist the twist: instant hemodynamic improvement in known HeartMate 3 complication.

The HeartMate 3 [HM3 (Abbott, Abbott Park, Illinois)] is a left-ventricular assist device (LVAD) with excellent clinical results. Outflow graft occlusion as a complication secondary to outflow graft twisting was reported to occur in 1.6% within the MOMENTUM 3 trial. The anti-twist metal clip or modified bend relief is made to prevent this complication currently, however, there remain large numbers of early implanted HM3 which may develop this complication. There are limited reports illustrating diagnosis, surgical repair, and post-repair hemodynamic changes of these complications. Thus, we present a case of successful diagnosis and surgical repair of an outflow graft twist. Simple procedure through thoracotomy without cardiopulmonary bypass provides significant immediate hemodynamic improvement.

Left thoracotomy vs full sternotomy for centrifugal durable LVAD implantation: 1-year outcome comparison post-LVAD and post-heart transplantation.

Left ventricular assist device (LVAD) implantations have traditionally been approached through a full median sternotomy (FS). Recently, a minimally invasive left thoracotomy (LT) approach has been popularized. This study sought to compare the outcomes of FS and LT patients post-primary LVAD implantation and post-subsequent heart transplant (HT). This was a single-center retrospective study. 83 patients who underwent primary centrifugal durable LVAD implantation from January 2014 to June 2018 were included (FS, n = 41; LT, n = 42). 41 patients had a subsequent HT (FS, n = 19; LT, n = 22). Pre-operative patient demographics, intraoperative variables, post-operative 1-year survival, length of hospital stay, complications, and outcomes for LVAD implantation and following HT were analyzed. Intraoperative data showed that the LT group had a 23.4% longer mean LVAD implant surgical time (p < 0.01). One-year post-LVAD survival was similar between the two groups (p = 0.05). Complication rates, with the exception of the rate of hemorrhagic stroke (p = 0.04) post-LVAD implant were similar. One-year survival post-HT was similar between groups (p = 0.35). Complication rates and mean length of hospital stay were also similar (p = 1.0) post-HT. Our study demonstrated that LT approach does not negatively affect post-LVAD implantation or post-HT outcomes. Further, larger studies may determine more detailed effects of LT approach.

Multi-phase catheter-injectable hydrogel enables dual-stage protein-engineered cytokine release to mitigate adverse left ventricular remodeling following myocardial infarction in a small animal model and a large animal model.

Although ischemic heart disease is the leading cause of death worldwide, mainstay treatments ultimately fail because they do not adequately address disease pathophysiology. Restoring the microvascular perfusion deficit remains a significant unmet need and may be addressed via delivery of pro-angiogenic cytokines. The therapeutic effect of cytokines can be enhanced by encapsulation within hydrogels, but current hydrogels do not offer sufficient clinical translatability due to unfavorable viscoelastic mechanical behavior which directly impacts the ability for minimally-invasive catheter delivery. In this report, we examine the therapeutic implications of dual-stage cytokine release from a novel, highly shear-thinning biocompatible catheter-deliverable hydrogel. We chose to encapsulate two protein-engineered cytokines, namely dimeric fragment of hepatocyte growth factor (HGFdf) and engineered stromal cell-derived factor 1α (ESA), which target distinct disease pathways. The controlled release of HGFdf and ESA from separate phases of the hyaluronic acid-based hydrogel allows extended and pronounced beneficial effects due to the precise timing of release. We evaluated the therapeutic efficacy of this treatment strategy in a small animal model of myocardial ischemia and observed a significant benefit in biological and functional parameters. Given the encouraging results from the small animal experiment, we translated this treatment to a large animal preclinical model and observed a reduction in scar size, indicating this strategy could serve as a potential adjunct therapy for the millions of people suffering from ischemic heart disease.

Development and Ex Vivo Validation of Novel Force-Sensing Neochordae for Measuring Chordae Tendineae Tension in the Mitral Valve Apparatus Using Optical Fibers With Embedded Bragg Gratings.

Few technologies exist that can provide quantitative data on forces within the mitral valve apparatus. Marker-based strain measurements can be performed, but chordal geometry and restricted optical access are limitations. Foil-based strain sensors have been described and work well, but the sensor footprint limits the number of chordae that can be measured. We instead utilized fiber Bragg grating (FBG) sensors-optical strain gauges made of 125 µm diameter silica fibers-to overcome some limitations of previous methods of measuring chordae tendineae forces. Using FBG sensors, we created a force-sensing neochord (FSN) that mimics the natural shape and movement of native chordae. FBG sensors reflect a specific wavelength of light depending on the spatial period of gratings. When force is applied, the gratings move relative to one another, shifting the wavelength of reflected light. This shift is directly proportional to force applied. The FBG sensors were housed in a protective sheath fashioned from a 0.025 in. flat coil, and attached to the chordae using polytetrafluoroethylene suture. The function of the force-sensing neochordae was validated in a three-dimensional (3D)-printed left heart simulator, which demonstrated that FBG sensors provide highly sensitive force measurements of mitral valve chordae at a temporal resolution of 1000 Hz. As ventricular pressures increased, such as in hypertension, chordae forces also increased. Overall, FBG sensors are a viable, durable, and high-fidelity sensing technology that can be effectively used to measure mitral valve chordae forces and overcome some limitations of other such technologies.

Heart Transplant Waitlist Outcomes and Wait Time by Center Volume in the Pre-2018 Allocation Change Era.

Although the transplant outcomes of centers are heavily monitored and compared, with a particular link between posttransplant outcomes and center volume demonstrated, little data exist comparing waitlist outcomes. Here, we explored waitlist outcomes by transplant center volume. We performed a retrospective analysis of adults listed for primary heart transplantation (HTx) from 2008 to 2018 using the United Network for Organ Sharing database. Transplant centers were split into low (<10 HTx/year), medium (10-30 HTx/year), and high (>30 HTx/year) volume, and waitlist outcomes were compared. Of the 35,190 patients included in our study, 23,726 (67.4%) underwent HTx, 4,915 (14.0%) died or deteriorated before receiving HTx, 1,356 (3.9%) were delisted due to recovery, and 1,336 (3.8%) underwent left ventricular assist device (LVAD) implantation. High-volume centers had higher rates of survival to transplant (71.3% vs. 60.6% for low-volume centers and 64.9% for medium-volume centers), and low rates of death or deterioration (12.6% vs. 14.6% for low-volume centers and 15.1% for medium-volume centers). Listing at a low-volume center was independently associated with death or delisting before HTx (HR 1.18, p = 0.007), whereas listing at a high-volume center (HR 0.86; p < 0.001) and prelisting LVAD (HR 0.67, p < 0.001) were protective. Death or delisting before HTx was lowest for patients listed in higher volume centers.

Career Progression and Research Productivity of Women in Academic Cardiothoracic Surgery.

BACKGROUND: The objective of this work was to delineate career progression and research productivity of women practicing cardiothoracic surgery in the academic setting. METHODS: Cardiothoracic surgeons at the 79 accredited US cardiothoracic surgery training programs in 2020 were included in this cross-sectional analysis. Data regarding subspecialization, training, practice history, and publications were gathered from public sources including department websites, CTSNet, and Scopus. RESULTS: A total of 1065 surgeons (51.3% cardiac, 32.1% thoracic, 16.6% congenital) were identified. Women accounted for 10.6% (113) of the population (7.9% of cardiac, 15.5% of thoracic, 9.6% of congenital surgeons). The median number of cardiothoracic surgeons per institution was 12 (interquartile range [IQR], 10-17), with a median of 1 woman (IQR, 0-2). Fifteen of 79 programs (19%) had no women. Among women faculty 5.3% were clinical instructors, 51.3% were assistant professors, 23.0% were associate professors, 16.8% were full professors, and 3.5% had unspecified titles (vs 2.0%, 32.9%, 23.0%, 37.5%, and 4.6% among men, respectively; P < .001). Women and men authored a comparable number of first-author (0.4 [IQR, 0.0-1.3] vs 0.5 [IQR, 0.0-1.1], P = .56) publications per year but fewer last-author (0.1 [IQR, 0.0-0.7] vs 0.4 [IQR, 0.0-1.3], P < .0001) and total publications per year (2.7 [IQR, 1.0-6.2] vs 3.7 [IQR, 1.3-7.8], P = .05) than men. The H-index was lower for women than for men overall (8.0 [IQR, 3.0-15.0] vs 15.0 [IQR, 7.0-28.0], P < .001) but was similar between men and women who had been practicing for 10 to 20 years. CONCLUSIONS: Gender disparities persist in academic cardiothoracic surgery. Efforts should be made to support women in achieving senior roles and academic productivity.

The Effects of Percutaneous Left Ventricular Assist Device Placement on Native Valve Competency.

Impella left ventricular assist devices (LVADs) (Abiomed, Danvers, MA) are implanted in the left ventricle across the aortic valve. Several cases of secondary aortic insufficiency (AI) or mitral regurgitation (MR) after Impella LVAD use have been reported. Secondary valvulopathies can worsen cardiac function. This single center retrospective study sought to characterize the incidence of secondary AI and MR development after Impella LVAD support. One hundred fifty-two patients who underwent Impella LVAD support between April 2014 and August 2019 were included. Patient demographics, implant indications, duration of support, pre- and post-Impella LVAD echocardiograms, and incidence of increased AI/MR were analyzed. Impella 5.0 and Impella CP were subanalyzed. Following exclusion criteria, AI and MR were analyzed in 93 and 78 patients, respectively. An increase in AI and MR was seen in 17.2% and 12.8% of patients with an event per support days of 0.03 and 0.02, respectively. Clinically significant increases in AI and MR were seen in 3.2% (n = 3), 6.4% (n = 5), respectively. The incidences of increased AI (p = 0.33) and MR (p = 0.45) were similar between Impella 5.0 and Impella CP patients. Worsening AI and MR clinically occur at a low incidence with Impella LVAD use. However, careful follow-up is still warranted.

A neonatal leporine model of age-dependent natural heart regeneration after myocardial infarction.

OBJECTIVES: Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction. METHODS: New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n = 94), postnatal day 4 (n = 11), or postnatal day 7 (n = 52). Hearts were explanted 1 day postsurgery to confirm ischemic injury, at 1 week postsurgery to assess cardiomyocyte proliferation, and at 3 weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean ± standard deviation. RESULTS: Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3% ± 5.4% vs 42.3% ± 4.7%, P = .9984). Echocardiography confirmed severely reduced ejection fraction at 1 day after postnatal day 1 myocardial infarction (33.7% ± 5.3% vs 65.2% ± 5.5% for postnatal day 1 sham, P = .0001), but no difference at 3 weeks after postnatal day 1 myocardial infarction (56.0% ± 4.0% vs 58.0% ± 3.3% for postnatal day 1 sham, P = .2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2% ± 1.8% vs 58.5% ± 5.8% for postnatal day 4 sham, P = .0109) and postnatal day 7 myocardial infarction (39.0% ± 7.8% vs 60.2% ± 5.0% for postnatal day 7 sham, P &lt; .0001). At 3 weeks after infarction, fibrotic scar represented 5.3% ± 1.9%, 14.3% ± 4.9%, and 25.4% ± 13.3% of the left ventricle area in the postnatal day 1, postnatal day 4, and postnatal day 7 groups, respectively. An increased proportion of peri-infarct cardiomyocytes expressed Ki67 (15.9% ± 1.8% vs 10.2% ± 0.8%, P = .0039) and aurora B kinase (4.0% ± 0.9% vs 1.5% ± 0.6%, P = .0088) after postnatal day 1 myocardial infarction compared with sham, but no increase was observed after postnatal day 7 myocardial infarction. CONCLUSIONS: A neonatal leporine myocardial infarction model reveals that newborn rabbits are capable of age-dependent natural heart regeneration.

Natural cardiac regeneration conserves native biaxial left ventricular biomechanics after myocardial infarction in neonatal rats.

After myocardial infarction (MI), adult mammals exhibit scar formation, adverse left ventricular (LV) remodeling, LV stiffening, and impaired contractility, ultimately resulting in heart failure. Neonatal mammals, however, are capable of natural heart regeneration after MI. We hypothesized that neonatal cardiac regeneration conserves native biaxial LV mechanics after MI. Wistar rat neonates (1 day old, n = 46) and adults (8-10 weeks old, n = 20) underwent sham surgery or permanent left anterior descending coronary artery ligation. At 6 weeks after neonatal MI, Masson's trichrome staining revealed negligible fibrosis. Echocardiography for the neonatal MI (n = 15) and sham rats (n = 14) revealed no differences in LV wall thickness or chamber diameter, and both groups had normal ejection fraction (72.7% vs 77.5%, respectively, p = 0.1946). Biaxial tensile testing revealed similar stress-strain curves along both the circumferential and longitudinal axes across a full range of physiologic stresses and strains. The circumferential modulus (267.9 kPa vs 274.2 kPa, p = 0.7847), longitudinal modulus (269.3 kPa vs 277.1 kPa, p = 0.7435), and maximum shear stress (3.30 kPa vs 3.95 kPa, p = 0.5418) did not differ significantly between the neonatal MI and sham groups, respectively. In contrast, transmural scars were observed at 4 weeks after adult MI. Adult MI hearts (n = 7) exhibited profound LV wall thinning (p < 0.0001), chamber dilation (p = 0.0246), and LV dysfunction (ejection fraction 45.4% vs 79.7%, p < 0.0001) compared to adult sham hearts (n = 7). Adult MI hearts were significantly stiffer than adult sham hearts in both the circumferential (321.5 kPa vs 180.0 kPa, p = 0.0111) and longitudinal axes (315.4 kPa vs 172.3 kPa, p = 0.0173), and also exhibited greater maximum shear stress (14.87 kPa vs 3.23 kPa, p = 0.0162). Our study is the first to show that native biaxial LV mechanics are conserved after neonatal heart regeneration following MI, thus adding biomechanical support for the therapeutic potential of cardiac regeneration in the treatment of ischemic heart disease.

Biodegradable external wrapping promotes favorable adaptation in an ovine vein graft model.

Vein grafts, the most commonly used conduits in multi-vessel coronary artery bypass grafting surgery, have high intermediate- and long-term failure rates. The abrupt and marked increase in hemodynamic loads on the vein graft is a known contributor to failure. Recent computational modeling suggests that veins can more successfully adapt to an increase in mechanical load if the rate of loading is gradual. Applying an external wrap or support at the time of surgery is one way to reduce the transmural load, and this approach has improved performance relative to an unsupported vein graft in several animal studies. Yet, a clinical trial in humans has shown benefits and drawbacks, and mechanisms by which an external wrap affects vein graft adaptation remain unknown. This study aims to elucidate such mechanisms using a multimodal experimental and computational data collection pipeline. We quantify morphometry using magnetic resonance imaging, mechanics using biaxial testing, hemodynamics using computational fluid dynamics, structure using histology, and transcriptional changes using bulk RNA-sequencing in an ovine carotid-jugular interposition vein graft model, without and with an external biodegradable wrap that allows loads to increase gradually. We show that a biodegradable external wrap promotes luminal uniformity, physiological wall shear stress, and a consistent vein graft phenotype, namely, it prevents over-distension, over-thickening, intimal hyperplasia, and inflammation, and it preserves mechanotransduction. These mechanobiological insights into vein graft adaptation in the presence of an external support can inform computational growth and remodeling models of external support and facilitate design and manufacturing of next-generation external wrapping devices. STATEMENT OF SIGNIFICANCE: External mechanical support is emerging as a promising technology to prevent vein graft failure following coronary bypass graft surgery. While variants of this technology are currently under investigation in clinical trials, the fundamental mechanisms of adaptation remain poorly understood. We employ an ovine carotid-jugular interposition vein graft model, with and without an external biodegradable wrap to provide mechanical support, and probe vein graft adaptation using a multimodal experimental and computational data collection pipeline. We quantify morphometry using magnetic resonance imaging, mechanics using biaxial testing, fluid flow using computational fluid dynamics, vascular composition and structure using histology, and transcriptional changes using bulk RNA sequencing. We show that the wrap mitigates vein graft failure by promoting multiple adaptive mechanisms (across biological scales).

Right ventricular undersizing is associated with increased 1-year mortality.

OBJECTIVES: Right heart hemodynamic management is critical, because many post-heart transplantation (HTx) complications are related to right ventricular (RV) failure. However, current guidelines on size and sex matching rely primarily on weight matching, with recent literature using total ventricular mass (TVM), which places less emphasis on the impact of RV mass (RVM) matching. The aim of the present study was to analyze the relationship of RVM matching and survival after HTx. METHODS: We performed the retrospective analysis using the UNOS database of adult HTx performed between January 1997 and December 2017. Previously validated equations were used to calculate TVM and RVM. The percent difference in ventricular mass in the donor and recipient pair was used for the size mismatch. All donor-recipient pairs were divided into 4 RVM groups by their mismatch ratio. We analyzed RVM matching and explored how RVM undersizing impacted outcomes. The primary outcome measure was 1-year survival; secondary outcomes measured included stroke and dialysis within 1 year and functional status. RESULTS: A total of 38,740 donor-recipient pairs were included in our study. The 4 RVM match groupings were as follows: <0%, 0% to 20%, 20% to 40%, and >40%. Utilization of donors who were older and of female sex resulted in greater RVM undersizing. Survival analysis demonstrated patients with RVM undersizing had worse 1-year survival (P < .001). RVM undersizing was an independent predictor of higher 1-year mortality (hazard ratio, 1.23; 95% confidence interval, 1.11 to 1.34; P < .001). RVM undersizing was also associated with higher rates of dialysis within 1-year of transplantation and poorer postoperative functional status. CONCLUSIONS: RVM undersizing is an independent predictor for worse 1-year survival. Donors who are older and female have lower absolute predicted RVM and may be predisposed to RVM undersizing. RVM-undersized transplantation requires careful risk/benefit considerations.

Women in Thoracic Surgery Scholarship: Impact on Career Path and Interest in Cardiothoracic Surgery.

BACKGROUND: Women remain underrepresented in cardiothoracic surgery (CTS). In 2005, Women in Thoracic Surgery (WTS) began offering scholarships to promote engagement of women in CTS careers. This study explores the effect of WTS scholarships on CTS career milestones. METHODS: We assessed career development using the number of awardees matching into CTS residency/fellowship, American Board of Thoracic Surgery (ABTS) certification, and academic CTS appointment. Scholarship awardee data were obtained from our WTS database. Comparison data were gathered from the National Residency Match Program and ABTS. Details of the current roles of ABTS-certified women were determined from public resources. Qualitative results were gathered from post-scholarship surveys. RESULTS: A total of 106 WTS scholarships have been awarded to 38 medical students (36%), 41 general surgery residents (39%), and 27 CTS residents/fellows (25%). Among medical students, 26% of awardees entered integrated CTS residency (vs <0.1% for medical students, P < .001), and 37% entered general surgery residency (vs 4.8% for medical students, P < .001). Of general surgery awardees, 59% entered CTS fellowships (vs 7.7% for general surgery residents, P < .001), and of CTS resident/fellow awardees, 100% earned ABTS certification (vs 73% ABTS pass rate, P = .01). Of ABTS-certified awardees, 44% are practicing cardiothoracic surgeons at US academic training institutions (vs 33% of non-awardee ABTS-certified women, P = .419). All awardees reported that their scholarship was valuable in their development. CONCLUSIONS: Receipt of a WTS scholarship is associated with successful pursuit of CTS career milestones at significantly higher rates than contemporaries. These scholarships foster a supportive community for women trainees in CTS.

Off-Pump Minithoracotomy Versus Sternotomy for Left Anterior Descending Myocardial Bridge Unroofing.

BACKGROUND: Myocardial bridge (MB) of the left anterior descending (LAD) coronary artery occurs in approximately 25% of the population. When medical therapy fails in patients with a symptomatic, hemodynamically significant MB, MB unroofing represents the optimal surgical management. Here, we evaluated minimally invasive MB unroofing in selected patients compared with sternotomy. METHODS: MB unroofing was performed in 141 adult patients by sternotomy on-pump (ST-on, n = 40), sternotomy off-pump (ST-off, n = 62), or minithoracotomy off-pump (MT, n = 39). Angina symptoms were assessed preoperatively and 6 months postoperatively using the Seattle Angina Questionnaire. Matching included all MT patients and 31 ST-off patients with similar MB characteristics, no previous cardiac operations or coronary interventions, and no concomitant procedures. RESULTS: MT patients tended to have a shorter MB length than ST-on and ST-off patients (2.57 vs 2.93 vs 3.09 cm, P = .166). ST-on patients had a longer hospital stay than ST-off and MT patients (5.0 vs 4.0 vs 3.0 days, P < .001), and more blood transfusions (15.2% vs 0.0% vs 2.6%, P = .002). After matching, MT patients had a shorter hospital stay than ST-off patients (3.0 vs 4.0 days, P = .005). No deaths or major complications occurred in any group. In all groups, MB unroofing yielded significant symptomatic improvement regarding physical limitation, angina stability, angina frequency, treatment satisfaction, and quality of life. CONCLUSIONS: We report our single-center experience of off-pump minimally invasive MB unroofing, which may be safely performed in carefully selected patients, yielding dramatic improvements in angina symptoms at 6 months after the operation.

A novel 3D-Printed preferential posterior mitral annular dilation device delineates regurgitation onset threshold in an ex vivo heart simulator.

Mitral regurgitation (MR) due to annular dilation occurs in a variety of mitral valve diseases and is observed in many patients with heart failure due to mitral regurgitation. To understand the biomechanics of MR and ultimately design an optimized annuloplasty ring, a representative disease model with asymmetric dilation of the mitral annulus is needed. This work shows the design and implementation of a 3D-printed valve dilation device to preferentially dilate the posterior mitral valve annulus. Porcine mitral valves (n = 3) were sewn into the device and mounted within a left heart simulator that generates physiologic pressures and flows through the valves, while chordal forces were measured. The valves were incrementally dilated, inducing MR, while hemodynamic and force data were collected. Flow analysis demonstrated that MR increased linearly with respect to percent annular dilation when dilation was greater than a 25.6% dilation threshold (p < 0.01). Pre-threshold, dilation did not cause significant increases in regurgitant fraction. Forces on the chordae tendineae increased as dilation increased prior to the identified threshold (p < 0.01); post-threshold, the MR resulted in highly variable forces. Ultimately, this novel dilation device can be used to more accurately model a wide range of MR disease states and their corresponding repair techniques using ex vivo experimentation. In particular, this annular dilation device provides the means to investigate the design and optimization of novel annuloplasty rings.

Mitral chordae tendineae force profile characterization using a posterior ventricular anchoring neochordal repair model for mitral regurgitation in a three-dimensional-printed ex vivo left heart simulator.

OBJECTIVES: Posterior ventricular anchoring neochordal (PVAN) repair is a non-resectional technique for correcting mitral regurgitation (MR) due to posterior leaflet prolapse, utilizing a single suture anchored in the myocardium behind the leaflet. This technique has demonstrated clinical efficacy, although a theoretical limitation is stability of the anchoring suture. We hypothesize that the PVAN suture positions the leaflet for coaptation, after which forces are distributed evenly with low repair suture forces. METHODS: Porcine mitral valves were mounted in a 3-dimensional-printed heart simulator and chordal forces, haemodynamics and echocardiography were collected at baseline, after inducing MR by severing chordae, and after PVAN repair. Repair suture forces were measured with a force-sensing post positioned to mimic in vivo suture placement. Forces required to pull the myocardial suture free were also determined. RESULTS: Relative primary and secondary chordae forces on both leaflets were elevated during prolapse (P < 0.05). PVAN repair eliminated MR in all valves and normalized chordae forces to baseline levels on anterior primary (0.37 ± 0.23 to 0.22 ± 0.09 N, P < 0.05), posterior primary (0.62 ± 0.37 to 0.14 ± 0.05 N, P = 0.001), anterior secondary (1.48 ± 0.52 to 0.85 ± 0.43 N, P < 0.001) and posterior secondary chordae (1.42 ± 0.69 to 0.59 ± 0.17 N, P = 0.005). Repair suture forces were minimal, even compared to normal primary chordae forces (0.08 ± 0.04 vs 0.19 ± 0.08 N, P = 0.002), and were 90 times smaller than maximum forces tolerated by the myocardium (0.08 ± 0.04 vs 6.9 ± 1.3 N, P < 0.001). DISCUSSION: PVAN repair eliminates MR by positioning the posterior leaflet for coaptation, distributing forces throughout the valve. Given extremely low measured forces, the strength of the repair suture and the myocardium is not a limitation.

Biomimetic six-axis robots replicate human cardiac papillary muscle motion: pioneering the next generation of biomechanical heart simulator technology.

Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitral valve leaflets for proper coaptation. As the ventricle contracts, the papillary muscles translate and rotate, impacting chordae and leaflet kinematics; this motion can be significantly affected in a diseased heart. In ex vivo heart simulation, an explanted valve is subjected to physiologic conditions and can be adapted to mimic a disease state, thus providing a valuable tool to quantitatively analyse biomechanics and optimize surgical valve repair. However, without the inclusion of papillary muscle motion, current simulators are limited in their ability to accurately replicate cardiac biomechanics. We developed and implemented image-guided papillary muscle (IPM) robots to mimic the precise motion of papillary muscles. The IPM robotic system was designed with six degrees of freedom to fully capture the native motion. Mathematical analysis was used to avoid singularity conditions, and a supercomputing cluster enabled the calculation of the system's reachable workspace. The IPM robots were implemented in our heart simulator with motion prescribed by high-resolution human computed tomography images, revealing that papillary muscle motion significantly impacts the chordae force profile. Our IPM robotic system represents a significant advancement for ex vivo simulation, enabling more reliable cardiac simulations and repair optimizations.

Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model.

Newborn mice and piglets exhibit natural heart regeneration after myocardial infarction (MI). Discovering other mammals with this ability would provide evidence that neonatal cardiac regeneration after MI may be a conserved phenotype, which if activated in adults could open new options for treating ischemic cardiomyopathy in humans. Here, we hypothesized that newborn rats undergo natural heart regeneration after MI. Using a neonatal rat MI model, we performed left anterior descending coronary artery ligation or sham surgery in one-day-old rats under hypothermic circulatory arrest (n = 74). Operative survival was 97.3%. At 1 day post-surgery, rats in the MI group exhibited significantly reduced ejection fraction (EF) compared to shams (87.1% vs. 53.0%, p < 0.0001). At 3 weeks post-surgery, rats in the sham and MI groups demonstrated no difference in EF (71.1% vs. 69.2%, respectively, p = 0.2511), left ventricular wall thickness (p = 0.9458), or chamber diameter (p = 0.7801). Masson's trichome and picrosirius red staining revealed minimal collagen scar after MI. Increased numbers of cardiomyocytes positive for 5-ethynyl-2'-deoxyuridine (p = 0.0072), Ki-67 (p = 0.0340), and aurora B kinase (p = 0.0430) were observed within the peri-infarct region after MI, indicating ischemia-induced cardiomyocyte proliferation. Overall, we present a neonatal rat MI model and demonstrate that newborn rats are capable of endogenous neocardiomyogenesis after MI.