Spatial distribution and network morphology of epicardial, endocardial, interstitial, and Purkinje cell-associated elastin fibers in porcine left ventricle.

Cardiac extracellular matrices (ECM) play crucial functional roles in cardiac biomechanics. Previous studies have mainly focused on collagen, the major structural ECM in heart wall. The role of elastin in cardiac mechanics, however, is poorly understood. In this study, we investigated the spatial distribution and microstructural morphologies of cardiac elastin in porcine left ventricles. We demonstrated that the epicardial elastin network had location- and depth-dependency, and the overall epicardial elastin fiber mapping showed certain correlation with the helical heart muscle fiber architecture. When compared to the epicardial layer, the endocardial layer was thicker and has a higher elastin-collagen ratio and a denser elastin fiber network; moreover, the endocardial elastin fibers were finer and more wavy than the epicardial elastin fibers, all suggesting various interface mechanics. The myocardial interstitial elastin fibers co-exist with the perimysial collagen to bind the cardiomyocyte bundles; some of the interstitial elastin fibers showed a locally aligned, hinge-like structure to connect the adjacent cardiomyocyte bundles. This collagen-elastin combination reflects an optimal design in which the collagen provides mechanical strength and elastin fibers facilitate recoiling during systole. Moreover, cardiac elastin fibers, along with collagen network, closely associated with the Purkinje cells, indicating that this ECM association could be essential in organizing cardiac Purkinje cells into "fibrous" and "branching" morphologies and serving as a protective feature when Purkinje fibers experience large deformations in vivo. In short, our observations provide a structural basis for future in-depth biomechanical investigations and biomimicking of this long-overlooked cardiac ECM component.

Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model.

Researchers have shown that adult zebrafish have the potential to regenerate 20% of the ventricular muscle within two months of apex resection, and neonatal mice have the capacity to regenerate their heart after apex resection up until day 7 after birth. The goal of this study was to determine if large mammals (porcine heart model) have the capability to fully regenerate a resected portion of the left ventricular apex during the neonatal stage, and if so, how long the regenerative potential persists. A total of 36 piglets were divided into the following groups: 0-day control and surgical groups and seven-day control and surgical groups. For the apex removal groups, each piglet was subjected to a partial wall thickness resection (~30% of the ventricular wall thickness). Heart muscle function was assessed via transthoracic echocardiograms; the seven-day surgery group experienced a decrease in ejection fraction and fractional shortening. Upon gross necropsy, for piglets euthanized four weeks post-surgery, all 0-day-old hearts showed no signs of scarring or any indication of the induced injury. Histological analysis confirmed that piglets in the 0-day surgery group exhibited various degrees of regeneration, with half of the piglets showing full regeneration and the other half showing partial regeneration. However, each piglet in the seven-day surgery group demonstrated epicardial fibrosis along with moderate to severe dissecting interstitial fibrosis, which was accompanied by an abundant collagenous extracellular matrix as the result of a scar formation in the resection site. Histology of one 0-day apex resection piglet (briefly lain on and accidentally killed by the mother sow three days post-surgery) revealed dense, proliferative mesenchymal cells bordering the fibrin and hemorrhage zone and differentiating toward immature cardiomyocytes. We further examined the heart explants at 5-days post-surgery (5D PO) and 1-week post-surgery (1W PO) to assess the repair progression. For the 0-day surgery piglets euthanized at 5D PO and 1W PO, half had abundant proliferating mesenchymal cells, suggesting active regeneration, while the other half showed increased extracellular collagen. The seven-day surgery piglets euthanized at 5D PO, and 1W PO showed evidence of greatly increased extracellular collagen, while some piglets had proliferating mesenchymal cells, suggesting a regenerative effort is ongoing while scar formation seems to predominate. In short, our qualitative findings suggest that the piglets lose the full myocardial regenerative potential by 7 days after birth, but greatly preserve the regenerative potential within 1 day post-partum.

The first 200 septal myectomies: Ensuring gold standard outcomes.

OBJECTIVES: Septal myectomy remains the gold standard treatment for symptomatic left ventricular outflow tract obstruction refractory to medical treatment. It is recommended that this operation be performed in dedicated hypertrophic obstructive cardiomyopathy centres by experienced surgeons. The septal myectomy option remains unavailable to many patients based solely on geography, including those who would clearly benefit more substantially from surgery than other therapeutic options. Here, we share our experience in starting new hypertrophic cardiomyopathy programmes. METHODS: We retrospectively reviewed initial septal myectomy experiences at two hypertrophic cardiomyopathy programmes starting in 2014. RESULTS: Two-hundred septal myectomies were performed. Mean age was 58.8 years and 51% were females. Advanced heart failure symptoms were present in 95.5% of patients and 23.5% had experienced syncope. Mean maximal intraventricular gradient was 89 mmHg and 48.5% underwent concomitant procedures at the time of septal myectomy. There was no perioperative (in-hospital or 30 days) mortality. Ninety-two per cent had provoked left ventricular gradients of ≤ 15 mmHg and 97% had none/mild mitral regurgitation at post-operative assessment. In our contemporary cohort, there were 2 (1%) intraoperative ventricular septal defects and 5% required a permanent pacemaker. CONCLUSIONS: Our early septal myectomy experience targeted a complex population, frequently in need of concomitant procedures. Abolition of left ventricular obstruction and resolution of systolic anterior motion mediated mitral regurgitation can be expected. The safety and efficacy of septal myectomy carried at hypertrophic cardiomyopathy centres by properly trained surgeons achieved the desired outcomes established by recent hypertrophic cardiomyopathy guidelines.

Structural and biomechanical characterizations of acellular porcine mitral valve scaffolds: anterior leaflets, posterior leaflets, and chordae tendineae.

Mitral valve (MV) tissue engineering is still in its early stage, and one major challenge in MV tissue engineering is to identify appropriate scaffold materials. With the potential of acellular MV scaffolds being demonstrated recently, it is important to have a full understanding of the biomechanics of the native MV components and their acellular scaffolds. In this study, we have successfully characterized the structural and mechanical properties of porcine MV components, including anterior leaflet (AL), posterior leaflet (PL), strut chordae, and basal chordae, before and after decellularization. Quantitative DNA assay showed more than 90% reduction in DNA content, and Griffonia simplicifolia (GS) lectin immunohistochemistry confirmed the complete lack of porcine α-Gal antigen in the acellular MV components. In the acellular AL and PL, the atrialis, spongiosa, and fibrosa trilayered structure, along with its ECM constitutes, i.e., collagen fibers, elastin fibers, and portion of GAGs, were preserved. Nevertheless, the ECM of both AL and PL experienced a certain degree of disruption, exhibiting a less dense, porous ECM morphology. The overall anatomical morphology of the strut and basal chordae were also maintained after decellularization, with longitudinal morphology experiencing minimum disruption, but the cross-sectional morphology exhibiting evenly-distributed porous structure. In the acellular AL and PL, the nonlinear anisotropic biaxial mechanical behavior was overall preserved; however, uniaxial tensile tests showed that the removal of cellular content and the disruption of structural ECM did result in small decreases in maximum tensile modulus, tissue extensibility, failure stress, and failure strain for both MV leaflets and chordae.

Matricellular Protein Cilp1 Promotes Myocardial Fibrosis in Response to Myocardial Infarction.

[Figure: see text].

The Infectious Tale of Aerococcal Aortic Endocarditis: Cardiac Pacing in Acute Aortic Insufficiency With Complete Heart Block as a Bridge to Aortic Valve Replacement.

Here, we describe a rare case of Aerococcus endocarditis causing aortic insufficiency and paravalvular abscess presenting as complete heart block and shock. A 76-year-old man with diabetes mellitus presented to the emergency department with fever and dyspnea. His temperature was 102.4°F, heart rate 59 beats per minute, blood pressure 105/44 mmHg, and oxygen saturation was 98% on 6L oxygen. Examination revealed bounding carotid pulses, a 2/6 early blowing diastolic murmur at the left lower sternal border, and diminished lung sounds at the bases. Laboratory data showed leukocytosis of 19.65 k/µL, blood urea nitrogen 72 mg/dL, creatinine 2.92 mg/dL, lactic acid 3.1 mmol/L, pro-B-type natriuretic peptide 15,342 pg/mL, high-sensitivity troponin 136 ng/L, aspartate aminotransferase 129 U/L, and alanine aminotransferase of 115 U/L. An electrocardiogram showed complete heart block, and a transvenous pacemaker was placed. A transesophageal echocardiogram revealed an aortic root abscess and severe aortic insufficiency secondary to Aerococcus urinae. Ventricular pacing was used to decrease aortic insufficiency and optimize computed tomography with gating to view the coronary arteries due to wall motion abnormalities seen on the transthoracic echocardiogram. His aortic valve was replaced, and a pacemaker was planned. Aortic valve Aerococcus endocarditis is rare and can lead to complete heart block and aortic insufficiency. Cardiac pacing improves hemodynamics by increasing heart rate and decreasing left ventricular end-diastolic pressure.

Biomechanical properties of acellular scar ECM during the acute to chronic stages of myocardial infarction.

After myocardial infarction (MI), the infarcted tissue undergoes dynamic and time-dependent changes. Previous knowledge on MI biomechanical alterations has been obtained by studying the explanted scar tissues. In this study, we decellularized MI scar tissue and characterized the biomechanics of the obtained pure scar ECM. By thoroughly removing the cellular content in the MI scar tissue, we were able to avoid its confounding effects. Rat MI hearts were obtained from a reliable and reproducible model based on permanent left coronary artery ligation (PLCAL). MI heart explants at various time points (15 min, 1 week, 2 weeks, 4 weeks, and 12 weeks) were subjected to decellularization with 0.1% sodium dodecyl sulfate solution for ~1-2 weeks to obtain acellular scar ECM. A biaxial mechanical testing system was used to characterize the acellular scar ECM under physiologically relevant loading conditions. After decellularization, large decrease in wall thickness was observed in the native heart ECM and 15 min scar ECM, implying the collapse of cardiomyocyte lacunae after removal of heart muscle fibers. For scar ECM 1 week, 2 weeks, and 4 weeks post infarction, the decrease in wall thickness after decellularization was small. For scar ECM 12 weeks post infarction, the reduction amount of wall thickness due to decellularization was minimal. We found that the scar ECM preserved the overall mechanical anisotropy of the native ventricle wall and MI scar tissue, in which the longitudinal direction is more extensible. Acellular scar ECM from 15 min to 12 weeks post infarction showed an overall stiffening trend in biaxial behavior, in which longitudinal direction was mostly affected and manifested with a decreased extensibility and increased modulus. This reduction trend of longitudinal extensibility also led to a decreased anisotropy index in the scar ECM from the acute to chronic stages of MI. The post-MI change in biomechanical properties of the scar ECM reflected the alterations of collagen fiber network, confirmed by the histology of scar ECM. In short, the reported structure-property relationship reveals how scar ECM biophysical properties evolve from the acute to chronic stages of MI. The obtained information will help establish a knowledge basis about the dynamics of scar ECM to better understand post-MI cardiac remodeling.

Effects of COVID-19 pandemic on cardiac surgery practice in 61 Hospitals worldwide: results of a survey.

BACKGROUND: The aim of this study was to investigate the impact of COVID-19 infection on cardiac surgery community and practice. METHODS: A 43-question survey was sent to cardiac surgery centers worldwide. The survey analyzed the prepandemic organization of the center, the center's response to Covid-19 in terms of re-organization pathways, surveillance methods, personal-protective equipment (PPE), and allowed surgical practice with results. RESULTS: Sixty-one out of 64 centers (95.3%) fulfilled the survey. One third of ICUs were transformed into COVID-19 dedicated-ICUs and one-third moved to another location inside the hospital. Negative-pressure rooms were available in 60.6% centers. Informative measures from hospital administration were received after the first COVID-19 admitted case in 36.1% and during the spread of the infection inside the hospital in 19.6%. Inadequate supply of PPE was common, with no COVID-surveillance of the medical personnel in 4.9% of centers. COVID-19 infected 7.4% of staff surgeons, 8.3% of residents and 9.5% of anesthetists. Cardiac surgery caseload declined in 93.4% centers. COVID-19 infection in patients receiving cardiac surgery resulted in 41-50% mortality in 9.5% centers, and 91-100% mortality in 4.7% centers. Successful weaning with survival from veno-venous extra corporeal membrane oxygenation (ECMO) and veno-arterial ECMO was <50% in 79.2% and 80.0% centers respectively. COVID-19 infection in transplanted patients was rare, with a reported mortality of 0.5% and 1% in one center each. CONCLUSIONS: There is room for improvement in hospital surveillance, informative measures and PPE to the personnel. These measurements will reduce current spread of COVID-19 infection among medical personnel and patients, helping the rump up of cardiac surgical practice.

Regional biaxial mechanical data of the mitral and tricuspid valve anterior leaflets.

The collective data associated with this article presents the biaxial mechanical behavior for six smaller, delimited regions of the mitral valve and tricuspid valve anterior leaflets. Each data set consists of five columns of data, specifically: (i) biaxial testing protocol ID, (ii) circumferential stretch, (iii) radial stretch, (iv) circumferential membrane tension, and (v) radial membrane tension. For further elaboration regarding methodologies or results of the biaxial mechanical characterization please refer to the companion article Laurence, 2019.

Epicardial prestrained confinement and residual stresses: a newly observed heart ventricle confinement interface.

The heart epicardial layer, with elastin as the dominant component, has not been well investigated, specifically on how it contributes to ventricular biomechanics. In this study, we revealed and quantitatively assessed the overall status of prestraining and residual stresses exerted by the epicardial layer on the heart left ventricle (LV). During porcine heart wall dissection, we discovered that bi-layered LV surface strips, consisting of an epicardial layer and cardiac muscle, always curled towards the epicardial side due to epicardial residual stresses. We hence developed a curling angle characterization technique to intuitively and qualitatively reveal the location-dependency and direction-dependency of epicardial residual stresses. Moreover, by combining prestrain measurement and biaxial mechanical testing, we were able to quantify the epicardial prestrains and residual stresses on the unpressurized intact LV. To investigate the potential mechanical effect of epicardial prestraining, a finite-element (FE) model has been constructed, and we demonstrate that it is the prestraining of the epicardial layer, not the epicardial layer alone, providing an additional resistance mechanism during LV diastolic expansion and ventricular wall protection by reducing myocardial stress. In short, our study on healthy, native porcine hearts has revealed an important phenomenon-the epicardial layer, rich in elastin, acts like a prestrained 'balloon' that wraps around the heart and functions as an extra confinement and protection interface. The obtained knowledge fills a gap in ventricular biomechanics and will help design novel biomimicking materials or prosthetic devices to target the maintenance/recreation of this ventricle confinement interface.

An investigation of regional variations in the biaxial mechanical properties and stress relaxation behaviors of porcine atrioventricular heart valve leaflets.

The facilitation of proper blood flow through the heart depends on proper function of heart valve components, and alterations to any component can lead to heart disease or failure. Comprehension of these valvular diseases is reliant on thorough characterization of healthy heart valve structures for use in computational models. Previously, computational models have treated these leaflet structures as a structurally and mechanically homogenous material, which may not be an accurate description of leaflet mechanical response. In this study, we aimed to characterize the mechanics of the heart valve leaflet as a structurally heterogenous material. Specifically, porcine mitral valve and tricuspid valve anterior leaflets were sectioned into six regions and biaxial mechanical tests with various loading ratios and stress-relaxation test were performed on each regional tissue sample. Three main findings from this study were summarized as follows: (i) the central regions of the leaflet had a more anisotropic nature than edge regions, (ii) the mitral valve anterior leaflet was more extensible in regions closer to the annulus, and (iii) there was variance in the stress-relaxation behavior among all six regions, with mitral valve leaflet tissue regions exhibiting a greater decay than the tricuspid valve regions. This study presents a novel investigation of the regional variations in the heart valve biomechanics that has not been comprehensively examined. Our results thus allow for a refinement of computational models for more accurately predicting diseased or surgically-intervened condition, where tissue heterogeneity plays an essential role in the heart valve function.

Incidence and variables associated with 30-day mortality after lung transplantation.

BACKGROUND: With the introduction of the lung allocation score (LAS), sicker patients are prioritized for lung transplantation (LT). There is a lack of data regarding variables independently associated with 30-day mortality after LT. METHODS: We queried the UNOS database for adult patients undergoing LT between 1989 and 2014. Patients with dual organ or previous transplantation and those with missing survival data were excluded. Mortality during the first 30 days after LT was the primary outcome variable. RESULTS: The yearly trends indicate a statistically significant reduction in the 30-day mortality during the study period (P < 0.001, overall mortality: 5.5%) which has continued in the post-LAS era (P = 0. 014, overall mortality: 3.6%). Among patients with 30-day mortality, "primary non-function" (n = 118, 72.8%) was reported as the most common etiology. Transplant indication of vascular diseases, history of non-transplant cardiac or lung surgery, mean pulmonary pressures >35 mm Hg, disabled functional status, ECMO support, high LAS, ischemic time >6 hours, and blunt injury as the mechanism of donor death are independently associated with 30-day mortality. CONCLUSION: The incidence of early mortality after LT continues to decline in the post-LAS era. Apart from the mechanism of donor death and ischemic time, early mortality appears to be primarily driven by the recipient characteristics.

Robotic-assisted microvascular surgery: skill acquisition in a rat model.

Microsurgery is a technically demanding field with long learning curves. Robotic-assisted microsurgery has the ability to decrease these learning curves. We, therefore, sought to assess the feasibility of robotic-assisted microvascular surgery in a rat model, and whether this could be translated into a worthwhile skills acquisition exercise for residents. Twenty-eight rats underwent microvascular anastomosis. Procedures were performed by a trained microvascular surgeon with no robotic experience (n = 14), or a trained robotic surgeon with no microvascular experience (n = 14). Anesthetized rats were subjected to complete transection and end-to-end anastomosis of the abdominal aorta using 10-0 prolene. Manually (n = 6) and robotic-assisted (n = 8) procedures were performed by both surgeons. A successful procedure required a patent anastomosis and no bleeding. After approximately 35 days, angiography and histopathological studies of the anastomoses were performed. Median times for robotic-assisted anastomoses were 37.5 (34.2-42.7) min for the microsurgeon and 38.5 (32.7-52) min for robotic surgeon. In the manual group, it took 17 (13.5-23) min for microsurgeon and 44 (34.5-60) min for robotic surgeon. Within the robotic-assisted group, there was a trend toward improvement in both surgeons, but greater in the microsurgeon. Robotic-assisted microvascular anastomosis in a rat model is a feasible skill acquisition exercise. By eliminating the need for a skilled microsurgical assistant, as well as, improved microsurgical technology, the robotic system may prove to be a crucial player in future microsurgical skill training.

Hypertrophic obstructive cardiomyopathy: review of surgical treatment.

Hypertrophic cardiomyopathy ranks among the most common congenital cardiac diseases, affecting up to 1 in 200 of the general population. When it causes left ventricular outflow tract obstruction, treatment is guided to reduce symptoms and the risk of sudden cardiac death. Pharmacologic therapy is the first-line treatment, but when it fails, surgical myectomy or percutaneous ablation of the hypertrophic myocardium are the standard therapies to eliminate subaortic obstruction. Both surgical myectomy and percutaneous ablation are proven safe and effective treatments; however, myectomy is the gold standard with a significantly lower complication rate and more complete and lasting reduction of left ventricular outflow tract obstruction.

Implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: an updated systematic review and meta-analysis of outcomes and complications.

BACKGROUND: Since the introduction of the implantable cardioverter-defibrillator (ICD) in patients with hypertrophic cardiomyopathy (HCM), the incidence of sudden cardiac death (SCD) has been significantly reduced. Given its widespread use, it is important to identify the outcomes associated with ICD use in patients with HCM. The present paper is a systematic review and meta-analysis of the rates of appropriate and inappropriate interventions, mortality, and device complications in HCM patients with an ICD. METHODS: We conducted a systematic review and meta-analysis on 27 studies reporting outcomes and complications after ICD implantation in patients with HCM. ICD interventions, device complications, and mortality were extracted for analysis. RESULTS: A total of 3,797 patients with HCM and ICD implantation were included (mean age, 44.5 years; 63% male), of which 83% of patients had an ICD for primary prevention of SCD. The cardiac mortality was 0.9% (95% CI: 0.7-1.3) per year and non-cardiac mortality was 0.8% (95% CI: 0.6-1.2) per year. Annualized appropriate intervention rate was 4.8% and annualized inappropriate intervention was 4.9%. The annual incidence of lead malfunction, lead displacement and infection was 1.4%, 1.3%, and 1.1%, respectively. CONCLUSIONS: ICD use in patients with HCM produces low rates of cardiac and non-cardiac mortality, and an appropriate intervention rate of 4.8% per year. However, moderate rates of inappropriate intervention and device complications warrant careful patient selection in order to optimize the risk to benefit ratio in this select group of patients.

Septal myectomy after failed septal alcohol ablation.

Despite septal myectomy remaining the gold standard septal reduction therapy for hypertrophic obstructive cardiomyopathy (HOCM), there has been a disproportionate use of alcohol septal ablation (ASA) worldwide. Absolute resolution of left ventricular outflow tract (LVOT) obstruction with ASA is not achieved in a substantial proportion of patients. The mechanisms of failure from ASA are partially understood and described. Residual obstruction in hypertrophic cardiomyopathy is associated with worse clinical outcomes and mortality. There is a growing number of patients who present with significant residual gradients after ASA and require a rescue septal myectomy operation, which then carries an increased risk of perioperative complications and life-long sequelae. This contrasts with the excellent outcomes achieved by septal myectomy without previous percutaneous intervention. Despite complete resolution of obstruction in rescue myectomy, the outcomes remain compromised by the prior ASA.