Search

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

OBJECTIVE: New transapical minimally invasive artificial chordae implantation devices are a promising alternative to traditional open-heart repair, with the potential for decreased postoperative morbidity and reduced recovery time. However, these devices can place increased stress on the artificial chordae. We designed an artificial papillary muscle to alleviate artificial chordae stresses and thus increase repair durability. METHODS: The artificial papillary muscle device is a narrow elastic column with an inner core that can be implanted during the minimally invasive transapical procedure via the same ventricular incision site. The device was 3-dimensionally printed in biocompatible silicone for this study. To test efficacy, porcine mitral valves (n = 6) were mounted in a heart simulator, and isolated regurgitation was induced. Each valve was repaired with a polytetrafluoroethylene suture with apical anchoring followed by artificial papillary muscle anchoring. In each case, a high-resolution Fiber Bragg Grating sensor recorded forces on the suture. RESULTS: Hemodynamic data confirmed that both repairs—with and without the artificial papillary muscle device—were successful in eliminating mitral regurgitation. Both the peak artificial chordae force and the rate of change of force at the onset of systole were significantly lower with the device compared with apical anchoring without the device (P < .001 and P < .001, respectively). CONCLUSIONS: Our novel artificial papillary muscle could integrate with minimally invasive repairs to shorten the artificial chordae and behave as an elastic damper, thus reducing sharp increases in force. With our device, we have the potential to improve the durability of off-pump transapical mitral valve repair procedures.

Objective The objective was to design and evaluate a clinically relevant, novel ex vivo bicuspid aortic valve model that mimics the most common human phenotype with associated aortic regurgitation. Methods Three bovine aortic valves were mounted asymmetrically in a previously validated 3–dimensional-printed left heart simulator. The non-right commissure and the non-left commissure were both shifted slightly toward the left–right commissure, and the left and right coronary cusps were sewn together. The left–right commissure was then detached and reimplanted 10 mm lower than its native height. Free margin shortening was used for valve repair. Hemodynamic status, high-speed videography, and echocardiography data were collected before and after the repair. Results The bicuspid aortic valve model was successfully produced and repaired. High-speed videography confirmed prolapse of the fused cusp of the baseline bicuspid aortic valve models in diastole. Hemodynamic and pressure data confirmed accurate simulation of diseased conditions with aortic regurgitation and the subsequent repair. Regurgitant fraction postrepair was significantly reduced compared with that at baseline (14.5 ± 4.4% vs 28.6% ± 3.4%; P = .037). There was no change in peak velocity, peak gradient, or mean gradient across the valve pre- versus postrepair: 293.3 ± 18.3 cm/sec versus 325.3 ± 58.2 cm/sec (P = .29), 34.3 ± 4.2 mm Hg versus 43.3 ± 15.4 mm Hg (P = .30), and 11 ± 1 mm Hg versus 9.3 ± 2.5 mm Hg (P = .34), respectively. Conclusions An ex vivo bicuspid aortic valve model was designed that recapitulated the most common human phenotype with aortic regurgitation. These valves were successfully repaired, validating its potential for evaluating valve hemodynamics and optimizing surgical repair for bicuspid aortic valves.

OBJECTIVES The severity of acute papillary muscle (PM) rupture varies according to the extent and site of the rupture. However, the haemodynamic effects of different rupture variations are still poorly understood. Using a novel ex vivo model, we sought to study acute PM rupture to improve clinical management. METHODS Using porcine mitral valves (n = 32) mounted within an ex vivo left heart simulator, PM rupture was simulated. The mitral valve was divided into quadrants for analysis according to the PM heads. Acute PM rupture was simulated by incrementally cutting from 1/3 to the total number of chordae arising from 1 PM head of interest. Haemodynamic parameters were measured. RESULTS Rupture >2/3 of the chordae from 1 given PM head or regurgitation fraction >60% led to markedly deteriorated haemodynamics. Rupture at the anterolateral PM had a stronger negative effect on haemodynamics than rupture at the posteromedial PM. Rupture occurring at the anterior head of the anterolateral PM led to more marked haemodynamic instability than rupture occurring at the other PM heads. CONCLUSIONS The haemodynamic effects of acute PM rupture vary considerably according to the site and extent of the rupture. Rupture of ≤2/3 of chordae from 1 PM head or rupture at the posteromedial PM lead to less marked haemodynamics effects, suggesting a higher likelihood of tolerating surgery. Rupture at the anterolateral PM, specifically the anterior head, rupture of >2/3 of chordae from 1 PM head or regurgitation fraction >60% led to marked haemodynamic instability, suggesting the potential benefit from bridging strategies prior to surgery.

Objective Mitral valve repair is the gold standard treatment for degenerative mitral regurgitation; however, a multitude of repair techniques exist with little quantitative data comparing these approaches. Using a novel ex vivo model, we sought to evaluate biomechanical differences between repair techniques. Methods Using porcine mitral valves mounted within a custom 3-dimensional–printed left heart simulator, we induced mitral regurgitation using an isolated P2 prolapse model by cutting primary chordae. Next, we repaired the valves in series using the edge-to-edge technique, neochordoplasty, nonresectional remodeling, and classic leaflet resection. Hemodynamic data and chordae forces were measured and analyzed using an incomplete counterbalanced repeated measures design with the healthy pre-prolapse valve as a control. Results With the exception of the edge-to-edge technique, all repair methods effectively corrected mitral regurgitation, returning regurgitant fraction to baseline levels (baseline 11.9% ± 3.7%, edge-to-edge 22.5% ± 6.9%, nonresectional remodeling 12.3% ± 3.0%, neochordal 13.4% ± 4.8%, resection 14.7% ± 5.5%, P < 0.01). Forces on the primary chordae were minimized using the neochordal and nonresectional techniques whereas the edge-to-edge and resectional techniques resulted in significantly elevated primary forces. Secondary chordae forces also followed this pattern, with edge-to-edge repair generating significantly higher secondary forces and leaflet resection trending higher than the nonresectional and neochord repairs. Conclusions Although multiple methods of degenerative mitral valve repair are used clinically, their biomechanical properties vary significantly. Nonresectional techniques, including leaflet remodeling and neochordal techniques, appear to result in lower chordal forces in this ex vivo technical engineering model.

Resource-scarce regions with serious COVID-19 outbreaks do not have enough ventilators to support critically ill patients, and these shortages are especially devastating in developing countries. To help alleviate this strain, we have designed and tested the accessible low-barrier in vivo-validated economical ventilator (ALIVE Vent), a COVID-19-inspired, cost-effective, open-source, in vivo-validated solution made from commercially available components. The ALIVE Vent operates using compressed oxygen and air to drive inspiration, while two solenoid valves ensure one-way flow and precise cycle timing. The device was functionally tested and profiled using a variable resistance and compliance artificial lung and validated in anesthetized large animals. Our functional test results revealed its effective operation under a wide variety of ventilation conditions defined by the American Association of Respiratory Care guidelines for ventilator stockpiling. The large animal test showed that our ventilator performed similarly if not better than a standard ventilator in maintaining optimal ventilation status. The FiO2, respiratory rate, inspiratory to expiratory time ratio, positive-end expiratory pressure, and peak inspiratory pressure were successfully maintained within normal, clinically validated ranges, and the animals were recovered without any complications. In regions with limited access to ventilators, the ALIVE Vent can help alleviate shortages, and we have ensured that all used materials are publicly available. While this pandemic has elucidated enormous global inequalities in healthcare, innovative, cost-effective solutions aimed at reducing socio-economic barriers, such as the ALIVE Vent, can help enable access to prompt healthcare and life saving technology on a global scale and beyond COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s42242-021-00164-1.

We sought to understand how leaflet forces change in response to annular dilation and leaflet tethering (LT) in single ventricle physiology. Explanted fetal bovine tricuspid valves were sutured onto image-derived annuli and ventricular mounts. Control valves (CON) were secured to a size-matched hypoplastic left heart syndrome (HLHS)-type annulus and compared to: (1) normal tricuspid valves secured to a size-matched saddle-shaped annulus, (2) HLHS-type annulus with LT, (3) HLHS-type annulus with annular dilation (dilation valves), or (4) a combined disease model with both dilation and tethering (disease valves). The specimens were tested in a systemic heart simulator at various single ventricle physiologies. Leaflet forces were measured using optical strain sensors sutured to each leaflet edge. Average force in the anterior leaflet was 43.2% lower in CON compared to normal tricuspid valves (P0.001). LT resulted in a 6.6% increase in average forces on the anterior leaflet (P = 0.04), 10.7% increase on the posterior leaflet (P = 0.03), and 14.1% increase on the septal leaflet (P0.001). In dilation valves, average septal leaflet forces increased relative to the CON by 42.2% (P = 0.01). In disease valves, average leaflet forces increased by 54.8% in the anterior leaflet (P0.001), 37.6% in the posterior leaflet (P = 0.03), and 79.9% in the septal leaflet (P0.001). The anterior leaflet experiences the highest forces in the normal tricuspid annulus under single ventricle physiology conditions. Annular dilation resulted in an increase in forces on the septal leaflet and LT resulted in an increase in forces across all 3 leaflets. Annular dilation and LT combined resulted in the largest increase in leaflet forces across all 3 leaflets.

Infection with the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may cause viral pneumonia and acute respiratory distress syndrome (ARDS). Treatment of ARDS often requires mechanical ventilation and may take weeks for resolution. In areas with a large outbreaks, there may be shortages of ventilators available. While rudimentary methods for ventilator splitting have been described, given the range of independent ventilatory settings required for each patient, this solution is suboptimal. Here, we describe a device that can split a ventilator among up to four patients while allowing for individualized settings. The device has been validated in vitro and in vivo .

Background Despite the superiority of mitral valve repair (MVr) over replacement for degenerative disease, repair rates vary widely across centers. Traveling to a mitral reference center (MRC) is 1 way to increase the odds of MVr. This study assessed the economic value (quality/cost) and long-term outcomes of distant referral to an MRC. Methods Among 746 mitral surgery patients between January 2011 and June 2013, low-risk patients with an ejection fraction greater than 40% undergoing isolated degenerative MVr were identified and included 26 out-of-state (DISTANT) and 104 in-state patients (LOCAL). Short- and long-term outcomes and institutional financial data (including travel expenses) were used to compare groups. National average and MRC-specific MVr rates, clinical outcomes, and marginal value of quality-adjusted life-years collected from The Society of Thoracic Surgeons database and Medicare estimates were used to perform a nationally representative cost-benefit analysis for distant referral. Results Age, ejection fraction, operative time, blood transfusions, and annuloplasty ring size did not differ between groups. Median charges were $76,022 for LOCAL and $74,171 for DISTANT (P = .35), whereas median payments (including travel expenses) were $57,795 for LOCAL and $58,477 for DISTANT (P = .70). Short- and long-term outcomes were similar between groups and median follow-up was 7.1 years. Estimated 5-year survival was 97% (96% for LOCAL and 100% for DISTANT; P = .24). Cost-benefit analysis showed a net benefit through distant referral to an MRC ranging from $436 to $6078 to the payer and $22,163 to $30,067 to the patient, combining for an estimated $22,599 to $32,528 societal benefit. Conclusions These data suggest that distant referral to an MRC is achievable and reasonable.

Introduction: Central venous catheters (CVCs) are often trimmed during heart transplantation and pediatric cardiac surgery. However, the risk of endothelial injury caused by the cut tip of the CVC has not been evaluated. We hypothesized that there is no difference in the degree of endothelial injury associated with trimmed CVCs versus standard untrimmed CVCs. Methods: In four adult male sheep, the left external jugular vein was exposed in three segments, one designated for an untouched control group, one for the trimmed CVC group, and one for the untrimmed CVC group. Trimmed and untrimmed CVC tips were rotated circumferentially within their respective segments to abrade the lumen of the vein. The vein samples were explanted, and two representative sections from each sample were analyzed using hematoxylin and eosin (H&E) staining, as well as with immunohistochemistry against CD31, von Willebrand factor (vWF), endothelial nitric oxide synthase (eNOS), and caveolin. Higher immunohistochemical stain distributions and intensities are associated with normal health and function of the venous endothelium. Data are presented as counts with percentages or as means with standard error. Results: H&E staining revealed no evidence of endothelial injury in 6/8 (75%) samples from the untouched control group, and no injury in 4/8 (50%) samples from both the trimmed and untrimmed CVC groups ( p = 0.504). In all remaining samples from each group, only mild endothelial injury was observed. Immunohistochemical analysis comparing trimmed CVCs versus untrimmed CVCs revealed no difference in the percentage of endothelial cells staining positive for CD31 (57.5% ± 7.2% vs 55.0% ± 9.2%, p = 0.982), vWF (73.8% ± 8.0% vs 62.5% ± 9.6%, p = 0.579), eNOS (66.3% ± 4.2% vs 63.8% ± 7.5%, p = 0.962), and caveolin (53.8% ± 5.0% vs 51.3% ± 4.4%, p = 0.922). There were no significant differences between the groups in the distributions of stain intensity for CD31, vWF, eNOS, and caveolin. Conclusion: Trimmed CVCs do not increase endothelial injury compared to standard untrimmed CVCs.

Supplemental Digital Content is available in the text., 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 (P5-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.

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.

One major challenge in generating reproducible aortic valve (AV) repair results is the inability to assess AV morphology under physiologic pressure. A transparent intraoperative AV visualization device was designed and manufactured.This device comprises an open proximal end, a cantilevered edge to allow attachment of the device to the aorta or graft, a distal viewing surface, and 2 side ports for fluid delivery and air removal.The performance of the device was evaluated ex vivo using normal porcine AV in situ (n = 3), porcine AV after valve-sparing aortic root replacement (VSARR) (n = 3), porcine pulmonary valve in the Ross procedure (n = 3), and in 3 patients who underwent VSARR. AV morphology was clearly visualized using the device in all experiments. In human subjects, the use of this device successfully showed cusp prolapse after the initial VSARR and effectively guided additional cusp repair.This device successfully allows for direct visual assessment of the AV apparatus under physiologic pressure. The use of this device can potentially increase the adoptability of AV repair in clinical practice.

Newborn mammals, including piglets, exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). The electrophysiologic properties of this naturally regenerated myocardium have not been examined. We hypothesized that epicardial conduction is preserved after P1 MI in piglets. Yorkshire-Landrace piglets underwent left anterior descending coronary artery ligation at age P1 (n = 6) or P7 (n = 7), After 7 weeks, cardiac magnetic resonance imaging was performed with late gadolinium enhancement for analysis of fibrosis. Epicardial conduction mapping was performed using custom 3D-printed high-resolution mapping arrays. Age- and weight-matched healthy pigs served as controls (n = 6). At the study endpoint, left ventricular (LV) ejection fraction was similar for controls and P1 pigs (46.4 ± 3.0% vs. 40.3 ± 4.9%, p = 0.132), but significantly depressed for P7 pigs (30.2 ± 6.6%, p < 0.001 vs. control). The percentage of LV myocardial volume consisting of fibrotic scar was 1.0 ± 0.4% in controls, 9.9 ± 4.4% in P1 pigs (p = 0.002 vs. control), and 17.3 ± 4.6% in P7 pigs (p < 0.001 vs. control, p = 0.007 vs. P1). Isochrone activation maps and apex activation time were similar between controls and P1 pigs (9.4 ± 1.6 vs. 7.8 ± 0.9 ms, p = 0.649), but significantly prolonged in P7 pigs (21.3 ± 5.1 ms, p < 0.001 vs. control, p < 0.001 vs. P1). Conduction velocity was similar between controls and P1 pigs (1.0 ± 0.2 vs. 1.1 ± 0.4 mm/ms, p = 0.852), but slower in P7 pigs (0.7 ± 0.2 mm/ms, p = 0.129 vs. control, p = 0.052 vs. P1). Overall, our data suggest that epicardial conduction dynamics are conserved in the setting of natural heart regeneration in piglets after P1 MI.

We identified an extremely rare congenital porcine type 0 lateral bicuspid aortic valve from a fresh porcine heart. Using a 3-dimensionally printed ex vivo left heart simulator, we analyzed valvular hemodynamics at baseline, in an aortic aneurysm disease model, and after valve-sparing root replacement. We showed that bicuspid aortic valve regurgitation due to aortic aneurysm can be successfully repaired without significant hemodynamic impairment using the valve-sparing root replacement technique in an individualized approach. Our results provide direct hemodynamic evidence supporting the use of valve-sparing root replacement for patients with bicuspid aortic valve regurgitation.

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 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.

Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, often leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient proangiogenic chemokine, preserves biaxial LV mechanical properties after MI. Male Wistar rats (n = 45) underwent sham surgery (n = 15) or permanent left anterior descending coronary artery ligation. Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n = 15) or ESA (6 μg/kg, n = 15), delivered at four standardized borderzone sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Tensile testing of the anterolateral LV wall was performed using a displacement-controlled biaxial load frame, and modulus was determined after constitutive modeling. At 4 weeks post-MI, compared to saline controls, ESA-treated hearts had greater wall thickness (1.68 ± 0.05 mm vs 1.42 ± 0.08 mm, p = 0.008), smaller end-diastolic LV internal dimension (6.88 ± 0.29 mm vs 7.69 ± 0.22 mm, p = 0.044), and improved ejection fraction (62.8 ± 3.0% vs 49.4 ± 4.5%, p = 0.014). Histologic analysis revealed significantly reduced infarct size for ESA-treated hearts compared to saline controls (29.4 ± 2.9% vs 41.6 ± 3.1%, p = 0.021). Infarcted hearts treated with ESA exhibited decreased modulus compared to those treated with saline in both the circumferential (211.5 ± 6.9 kPa vs 264.3 ± 12.5 kPa, p = 0.001) and longitudinal axes (194.5 ± 6.5 kPa vs 258.1 ± 14.4 kPa, p < 0.001). In both principal directions, ESA-treated infarcted hearts possessed similar tissue compliance as sham non-infarcted hearts. Overall, intramyocardial ESA therapy improves post-MI ventricular remodeling and function, reduces infarct size, and preserves native LV biaxial mechanical properties.

CENTRAL MESSAGE : We present a video that depicts the continuous spectrum of anatomic relationships in normal, type 1, and type 0 bicuspid aortic valves. [...]

Annuloplasty ring choice and design are critical to the long-term efficacy of mitral valve (MV) repair. DynaRing is a selectively compliant annuloplasty ring composed of varying stiffness elastomer segments, a shape-set nitinol core, and a cross diameter filament. The ring provides sufficient stiffness to stabilize a diseased annulus while allowing physiological annular dynamics. Moreover, adjusting elastomer properties provides a mechanism for effectively tuning key MV metrics to specific patients. We evaluate the ring embedded in porcine valves with an ex-vivo left heart simulator and perform a 150 million cycle fatigue test via a custom oscillatory system. We present a patient-specific design approach for determining ring parameters using a finite element model optimization and patient MRI data. Ex-vivo experiment results demonstrate that motion of DynaRing closely matches literature values for healthy annuli. Findings from the patient-specific optimization establish DynaRing's ability to adjust the anterior–posterior and intercommissural diameters and saddle height by up to 8.8%, 5.6%, 19.8%, respectively, and match a wide range of patient data.

Introduction: Beating-heart transapical mitral valve repair represents a significant advancement in the minimally invasive treatment of mitral regurgitation. However, current techniques require increased artificial chordae length and altered anchoring position, which may increase the stresses on the suture. We hypothesized that artificial chordae manufactured with increased elasticity will dampen sharp increases in force, thus theoretically increasing durability. Methods: Porcine mitral valves (n=3) were mounted in a heart simulator and isolated mitral regurgitation was induced by cutting posterior primary chordae. Each valve was first repaired with standard CV-5 polytetrafluoroethylene (PTFE) suture affixed to a 3D-printed anchor with an embedded high-resolution Fiber Bragg Grating sensor to measure forces (Fig A). The repair was then repeated with an elastic suture manufactured using a biocompatible silicone and designed with a cross-sectional area of 0.56mm 2 , a geometry calculated to result in a desired 10-15% strain at relevant forces (Fig B). Results: Both materials allowed for successful repairs: mitral leakage volume was reduced from 28.29±4.83ml to 1.26±0.99ml ( p =0.009) with PTFE suture, and to 1.78±0.88ml ( p =0.008) with the elastic suture, with no significant difference between the repairs. Normalized force tracings (Fig C, standard deviation is shaded) revealed that the elastic suture resulted in a significantly lower peak systolic force when compared to PTFE suture (0.23±0.04N vs 0.32±0.03N, p =0.007). Conclusions: Artificial chordae with increased elasticity compared to traditional PTFE suture can dampen sharp peaks in force, thus offering a promising advancement in improving transapical repair durability. This proposal has the potential to apply to open-heart artificial chordae implantation as well. Future work to optimize suture material and manufacturability will help translate this development into clinical use.

Introduction: Advances in ex vivo heart simulation have enabled the study of valvular biomechanics, disease pathologies, and repair strategies. However, these simulators test the valves in isolation, which does not fully replicate in vivo physiology. We hypothesize that by engineering a simulator that preserves the aortomitral junction, we can better recreate pathophysiologies such as systolic anterior motion (SAM). Here, we present a new heart simulator that preserves and manipulates the native aortomitral physiology. Methods: Our simulator is comprised of three subsystems: the ventricular chamber, atrial chamber, and aortic chamber (Fig A, B). The heart is excised at the apex to preserve the papillary muscles, and the left ventricle, atrial cuff, and aorta are fixed to their respective chambers via hemostatic suturing to 3D-printed elastomeric rings. The chambers are equipped with pressure and flow sensors, and a linear piston pump generates physiologic pressures and flows. The atrial and aortic chambers are mounted on 5-degree-of-freedom arms. To demonstrate system function, we manipulated the aortomitral angle and measured aortic cardiac output. Results: In our testing, we evaluated two unique configurations of an explanted porcine heart, of which the aortomitral angles spanned the SAM predictive risk threshold of Conclusions: This work highlights the design and development of an ex vivo heart simulator capable of modeling native aortomitral physiology. Our results point to a clear direction for future experimentation, particularly evaluating the biomechanical changes of the heart based on the aortomitral angle. Future work will utilize this platform to create new models and repair techniques to ultimately improve clinical care of valvular pathologies.

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.

Introduction: Newborn piglets reportedly exhibit natural heart regeneration after myocardial infarction (MI). However, the electrophysiologic properties of this regenerated muscle have not been examined. We hypothesized that epicardial electrical conduction is preserved after MI in newborn piglets. Methods: Yorkshire-Landrace piglets underwent left anterior descending coronary artery ligation on postnatal day 1 (P1, n=4) or postnatal day 7 (P7, n=7), infarcting the anteroseptal left ventricle through which the Purkinje conduction system passes. After 7 weeks, cardiac magnetic resonance imaging (MRI) was performed with late gadolinium enhancement for fibrosis analysis. Epicardial conduction mapping was performed using custom 3D-printed, 256-channel high-resolution mapping arrays (Fig 1A). Age- and weight-matched healthy pigs served as controls (n=7). Data are expressed as mean±SD. Results: MRI analysis revealed significant differences between the control, P1, and P7 groups in ejection fraction (47.6±3.1% vs 37.6±3.3% vs 30.2±6.6%, p Conclusion: P1 piglets exhibited incomplete natural cardiac regeneration after MI but nevertheless demonstrated electrophysiologic conservation of epicardial conduction dynamics.

The need for personal protective equipment during the COVID-19 pandemic is far outstripping our ability to manufacture and distribute these supplies to hospitals. In particular, the medical N95 mask shortage is resulting in healthcare providers reusing masks or utilizing masks with filtration properties that do not meet medical N95 standards. We developed a solution for immediate use: a mask adaptor, outfitted with a quarter section of an N95 respirator that maintains the N95 seal standard, thereby quadrupling the N95 supply. A variety of designs were 3D-printed and optimized based on the following criteria: seal efficacy, filter surface area and N95 respirator multiplicity. The final design is reusable and features a 3D-printed soft silicone base as well as a rigid 3D-printed cartridge to seal one-quarter of a 3M 1860 N95 mask. Our mask passed the computerized N95 fit test for six individuals. All files are publicly available with this publication. Our design can provide immediate support for healthcare professionals in dire need of medical N95 masks by extending the current supply by a factor of four.

The clinical efficacy of neuregulin (NRG) in the treatment of heart failure is hindered by off-target exposure due to systemic delivery. We previously encapsulated neuregulin in a hydrogel (HG) for targeted and sustained myocardial delivery, demonstrating significant induction of cardiomyocyte proliferation and preservation of post-infarct cardiac function in a murine myocardial infarction (MI) model. Here, we performed a focused evaluation of our hydrogel-encapsulated neuregulin (NRG-HG) therapy’s potential to enhance cardiac function in an ovine large animal MI model. Adult male Dorset sheep (n = 21) underwent surgical induction of MI by coronary artery ligation. The sheep were randomized to receive an intramyocardial injection of saline, HG only, NRG only, or NRG-HG circumferentially around the infarct borderzone. Eight weeks after MI, closed-chest intracardiac pressure–volume hemodynamics were assessed, followed by heart explant for infarct size analysis. Compared to each of the control groups, NRG-HG significantly augmented left ventricular ejection fraction (p = 0.006) and contractility based on the slope of the end-systolic pressure–volume relationship (p = 0.006). NRG-HG also significantly reduced infarct scar size (p = 0.002). Overall, using a bioengineered hydrogel delivery system, a one-time dose of NRG delivered intramyocardially to the infarct borderzone at the time of MI in adult sheep significantly reduces scar size and enhances ventricular contractility at 8 weeks after MI.

Mitral valve (MV) annular dynamics are critical to the long term efficacy of MV repair. Today’s annuloplasty rings, used to restore MV function, impose significant constraints on the motion profile of the MV annulus. We present a selectively compliant ring that provides sufficient stiffness to stabilize a diseased annulus while allowing physiological annular dynamics. Ring design is informed by a finite element analysis and experimentally evaluated with in-vitro stereophotogrammetry. We compare the ring dynamics to commercially available semi-rigid rings as well as values found in literature for healthy annuli. The results demonstrate that motion of the selectively compliant ring is significantly closer to that of a healthy annulus based on standard metrics that define MV annular movement. Specifically, the metrics for the new ring compare to those in literature as follows: change in orifice area 12.5 ± 3% vs.10 ± 2%; change in anterior-posterior diam. 5.4 ± 0.3% vs. 7 ± 1%; change in inter-commissural diam. 6.6 ± 1.3% vs. 5 ± 1%.

Neonatal mice exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). Cardiac biomechanics intricately affect long-term heart function, but whether regenerated cardiac muscle is biomechanically similar to native myocardium remains unknown. We hypothesized that neonatal heart regeneration preserves native left ventricular (LV) biomechanical properties after MI. C57BL/6J mice underwent sham surgery or left anterior descending coronary artery ligation at age P1 or P7. Echocardiography performed 4 weeks post-MI showed that P1 MI and sham mice (n = 22, each) had similar LV wall thickness, diameter, and ejection fraction (59.6% vs 60.7%, p = 0.6514). Compared to P7 shams (n = 20), P7 MI mice (n = 20) had significant LV wall thinning, chamber enlargement, and depressed ejection fraction (32.6% vs 61.8%, p ex vivo, and the multiaxial lenticular stress-strain relationship was tracked. While LV tissue modulus for P1 MI and sham mice were similar (341.9 kPa vs 363.4 kPa, p = 0.6140), the modulus for P7 MI mice was significantly greater than that for P7 shams (691.6 kPa vs 429.2 kPa, p = 0.0194). We conclude that, in neonatal mice, regenerated LV muscle has similar biomechanical properties as native LV myocardium.

Although ex vivo simulation is a valuable tool for surgical optimization, a disease model that mimics human aortic regurgitation (AR) from cusp prolapse is needed to accurately examine valve biomechanics. To simulate AR, four porcine aortic valves were explanted, and the commissure between the two largest leaflets was detached and re-implanted 5 mm lower to induce cusp prolapse. Four additional valves were tested in their native state as controls. All valves were tested in a heart simulator while hemodynamics, high-speed videography, and echocardiography data were collected. Our AR model successfully reproduced cusp prolapse with significant increase in regurgitant volume compared with that of the controls (23.2 ± 8.9 versus 2.8 ± 1.6 ml, p = 0.017). Hemodynamics data confirmed the simulation of physiologic disease conditions. Echocardiography and color flow mapping demonstrated the presence of mild to moderate eccentric regurgitation in our AR model. This novel AR model has enormous potential in the evaluation of valve biomechanics and surgical repair techniques. Graphical Abstract.

OBJECTIVE. Barlow’s disease remains challenging to repair given the complex valvular morphology and lack of quantitative data comparing techniques. Though there have been recent strides in ex vivo evaluation of cardiac mechanics, to the best of our knowledge, there is no disease model that accurately simulates the morphology and pathophysiology of Barlow’s disease. The purpose of this study was to design such a model. METHOD. To simulate Barlow’s disease, a cross-species ex vivo model was developed. Bovine mitral valves (n=4) were sewn into a porcine annulus mount to create excess leaflet tissue and elongated chordae. A heart simulator generated physiologic conditions while hemodynamic data, high-speed videography, and chordal force measurements were collected. The regurgitant valves were repaired using nonresectional repair techniques such as neochord placement. RESULTS: The model successfully imitated the complexities of Barlow’s disease, including redundant, billowing bi-leaflet tissues with notable regurgitation. After repair, hemodynamic data confirmed reduction of mitral leakage volume 25.9±2.9 vs 2.1±1.8 mL, p

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 &lt, 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&rsquo, s trichome and picrosirius red staining revealed minimal collagen scar after MI. Increased numbers of cardiomyocytes positive for 5-ethynyl-2&prime, 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.

Summary The cyanobacterium Synechococcus elongatus (SE) has been shown to rescue ischaemic heart muscle after myocardial infarction by photosynthetic oxygen production. Here, we investigated SE toxicity and hypothesized that systemic SE exposure does not elicit a significant immune response in rats. Wistar rats intravenously received SE (n = 12), sterile saline (n = 12) or E. coli lipopolysaccharide (LPS, n = 4), and a subset (8 SE, 8 saline) received a repeat injection 4 weeks later. At baseline, 4 h, 24 h, 48 h, 8 days and 4 weeks after injection, clinical assessments, blood cultures, blood counts, lymphocyte phenotypes, liver function tests, proinflammatory cytokines and immunoglobulins were assessed. Across all metrics, SE rats responded comparably to saline controls, displaying no clinically significant immune response. As expected, LPS rats exhibited severe immunological responses. Systemic SE administration does not induce sepsis or toxicity in rats, thereby supporting the safety of cyanobacteria–mammalian symbiotic therapeutics using this organism., The cyanobacterium Synechococcus elongatus (SE) has been shown to rescue ischemic heart muscle after myocardial infarction by photosynthetic oxygen production. Here, we investigate SE toxicity by systemically administering SE to rats and evaluating their immune response by way of clinical assessments, blood cultures, blood counts, lymphocyte phenotypes, liver function tests, proinflammatory cytokines, immunoglobulins, and tissue histology. Systemic SE administration does not induce sepsis or toxicity in rats, thereby supporting the safety of cyanobacteria‐mammalian symbiotic therapeutics using this organism.

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.

Stromal cell-derived factor 1-alpha (SDF) is a potent bone marrow chemokine capable of recruiting circulating progenitor populations to injured tissue. SDF has known angiogenic capabilities, however, bone marrow-derived cellular contributions to tissue regeneration remain controversial. Bone marrow from DsRed transgenic donors was transplanted into recipients to lineage trace circulating cells after myocardial infarction (MI). SDF was delivered post-MI and hearts were evaluated for recruitment and plasticity of bone marrow-derived populations. SDF treatment improved ventricular function, border zone vessel density, and CD31+ cell frequency post-MI. Bone marrow-derived endothelial cells were observed; these cells arose through both cell fusion and transdifferentiation. Circulating cells also adopted cardiomyocyte fates, but such events were exceedingly rare and almost exclusively resulted from cell fusion. SDF did not significantly alter the proportion of circulating cells that adopted non-hematopoietic fates. Mechanistic insight into the governance of circulating cells is essential to realizing the full potential of cytokine therapies.

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.

Introduction: Neonatal mice exhibit natural heart regeneration after myocardial infarction (MI) until postnatal day 7 (P7). Whether this regenerated muscle is similar biomechanically to native myocardium remains unknown. We hypothesized that neonatal heart regeneration preserves native left ventricular (LV) biomechanical properties after MI. Methods: C57BL/6J mice (n=58) underwent sham surgery or left anterior descending coronary artery ligation on postnatal day 1 (P1) or P7. After 4 weeks, echocardiography was performed. The explanted anterolateral LV wall was mounted for lenticular hydrostatic deformation testing (Fig 1A-B) and pressurized to 130 mmHg with 37°C saline to impart a homogeneous stress load. Surface strain was tracked to calculate a multiaxial composite tissue modulus. Data are expressed as mean±SEM. Results: P1 MI and sham mice (n=14, each) had similar post-MI LV wall thickness (0.61±0.05 cm vs 0.66±0.03 cm, p=0.39), end-diastolic diameter (3.14±0.10 cm vs 3.05±0.12 cm, p=0.57), and ejection fraction (58.2±4.1% vs 55.2±4.4%, p=0.63). P7 MI mice (n=14) had significant LV wall thinning (0.40±0.04 cm vs 0.71±0.02 cm, p Conclusion: In a neonatal mouse MI model, regenerated LV muscle has similar biomechanical properties as native LV muscle.

In recent years, advances in medical imaging and three-dimensional (3D) additive manufacturing techniques have increased the use of 3D-printed anatomical models for surgical planning, device design and testing, customization of prostheses, and medical education. Using 3D-printing technology, we generated patient-specific models of mitral valves from their pre-operative cardiac imaging data and utilized these custom models to educate patients about their anatomy, disease, and treatment. Clinical 3D transthoracic and transesophageal echocardiography images were acquired from patients referred for mitral valve repair surgery and segmented using 3D modeling software. Patient-specific mitral valves were 3D-printed using a flexible polymer material to mimic the precise geometry and tissue texture of the relevant anatomy. 3D models were presented to patients at their pre-operative clinic visit and patient education was performed using either the 3D model or the standard anatomic illustrations. Afterward, patients completed questionnaires assessing knowledge and satisfaction. Responses were calculated based on a 1–5 Likert scale and analyzed using a nonparametric Mann–Whitney test. Twelve patients were presented with a patient-specific 3D-printed mitral valve model in addition to standard education materials and twelve patients were presented with only standard educational materials. The mean survey scores were 64.2 (±1.7) and 60.1 (±5.9), respectively (p = 0.008). The use of patient-specific anatomical models positively impacts patient education and satisfaction, and is a feasible method to open new opportunities in precision medicine.

Degenerative mitral valve disease is a common cause of mitral regurgitation and results in significant morbidity and mortality. Mitral valve repair is preferred over valve replacement given improvements in survival, left ventricular function, and freedom from reoperation. The purpose of this chapter is to provide surgeons with a comprehensive overview of various strategies available to successfully repair degenerative mitral valve disease. A brief overview of pertinent surgical anatomy is followed by a discussion on operative strategy and approach, with emphasis on minimally invasive techniques. Techniques to repair posterior, anterior, and bileaflet prolapse are discussed, along with some special scenarios. The chapter concludes with an overview on evaluating the repair, postoperative care, and pearls and pitfalls.

Background: Cardiovascular bypass grafting is an essential treatment for complex cases of atherosclerotic disease. Because the availability of autologous arterial and venous conduits is patient-limited, self-assembled cell-only grafts have been developed to serve as functional conduits with off-the-shelf availability. The unacceptably long production time required to generate these conduits, however, currently limits their clinical utility. Here, we introduce a novel technique to significantly accelerate the production process of self-assembled engineered vascular conduits. Methods: Human aortic smooth muscle cells and skin fibroblasts were used to construct bilevel cell sheets. Cell sheets were wrapped around a 22.5-gauge Angiocath needle to form tubular vessel constructs. A thin, flexible membrane of clinically approved biodegradable tissue glue (Dermabond Advanced) served as a temporary, external scaffold, allowing immediate perfusion and endothelialization of the vessel construct in a bioreactor. Subsequently, the matured vascular conduits were used as femoral artery interposition grafts in rats (n=20). Burst pressure, vasoreactivity, flow dynamics, perfusion, graft patency, and histological structure were assessed. Results: Compared with engineered vascular conduits formed without external stabilization, glue membrane–stabilized conduits reached maturity in the bioreactor in one-fifth the time. After only 2 weeks of perfusion, the matured conduits exhibited flow dynamics similar to that of control arteries, as well as physiological responses to vasoconstricting and vasodilating drugs. The matured conduits had burst pressures exceeding 500 mm Hg and had sufficient mechanical stability for surgical anastomoses. The patency rate of implanted conduits at 8 weeks was 100%, with flow rate and hind-limb perfusion similar to those of sham controls. Grafts explanted after 8 weeks showed a histological structure resembling that of typical arteries, including intima, media, adventitia, and internal and external elastic membrane layers. Conclusions: Our technique reduces the production time of self-assembled, cell sheet–derived engineered vascular conduits to 2 weeks, thereby permitting their use as bypass grafts within the clinical time window for elective cardiovascular surgery. Furthermore, our method uses only clinically approved materials and can be adapted to various cell sources, simplifying the path toward future clinical translation.

Introduction: Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, ultimately leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Methods: Male Wistar rats (n=46) underwent sham surgery (n=15) or permanent left anterior descending coronary artery ligation (n=31). Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n=15) or ESA (6 μg/kg, n=16), delivered at standardized peri-infarct sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Biaxial tensile testing of the anterior LV wall was performed using a strain-controlled biaxial load frame (Fig. 1A), producing up to physiologic circumferential and longitudinal strains (ε=20%, each). The modulus was determined along each axis, and maximum shear stress was calculated as a composite metric of the tissue’s response to physiologic strains. Data are expressed as mean±SEM. Results: At 4 weeks post-MI, ESA-treated hearts had smaller end-diastolic LV internal dimension (6.89±0.27 cm vs 7.69±0.22 cm, p=0.03) and improved ejection fraction (63.7±2.9% vs 49.4±4.4%, p=0.01) compared to saline-injected controls. Hearts treated with ESA exhibited lower moduli than saline controls in both the circumferential (269.4±33.2 kPa vs 431.5±55.6 kPa, p=0.02) and longitudinal axes (182.4±25.0 kPa vs 332.3±51.2 kPa, p=0.02, Fig. 1B). The maximum shear stress for ESA-treated hearts was significantly reduced compared to that for saline controls (5.8±0.8 kPa vs 9.0±1.2 kPa, p=0.03) and was similar to that for sham controls (Fig. 1C). Conclusion: Intramyocardial ESA injection mitigates post-MI tissue stiffening and preserves biaxial LV mechanical properties.