3D Imaging Reveals Complex Microvascular Remodeling in the Right Ventricle in Pulmonary Hypertension.

BACKGROUND: Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure. METHODS: Heart sections measuring 250-µm-thick were obtained from mice after pulmonary artery banding (PAB) or debanding PAB surgery and properties of the RV microvascular network were assessed using 3D imaging and quantification. Human heart tissues harvested at the time of transplantation from pulmonary arterial hypertension cases were compared with tissues from control cases with normal RV function. RESULTS: Longitudinal 3D assessment of PAB mouse hearts uncovered complex microvascular remodeling characterized by tortuous, shorter, thicker, highly branched vessels, and overall preserved microvascular density. This remodeling process was reversible in debanding PAB mice in which the RV function recovers over time. The remodeled microvasculature tightly wrapped around the hypertrophied cardiomyocytes to maintain a stable contact surface to cardiomyocytes as an adaptation to RV pressure overload, even in end-stage RV failure. However, microvasculature-cardiomyocyte contact was impaired in areas with interstitial fibrosis where cardiomyocytes displayed signs of hypoxia. Similar to PAB animals, microvascular density in the RV was preserved in patients with end-stage pulmonary arterial hypertension, and microvascular architectural changes appeared to vary by etiology, with patients with pulmonary veno-occlusive disease displaying a lack of microvascular complexity with uniformly short segments. CONCLUSIONS: 3D deep tissue imaging of the failing RV in PAB mice, pulmonary hypertension rats, and patients with pulmonary arterial hypertension reveals complex microvascular changes to preserve the microvascular density and maintain a stable microvascular-cardiomyocyte contact. Our studies provide a novel framework to understand microvascular adaptation in the pressure-overloaded RV that focuses on cell-cell interaction and goes beyond the concept of capillary rarefaction.

Blood transfusion in aortic root surgery impairs midterm survival.

Objective: To evaluate the effect of perioperative allogeneic packed red blood cell (RBC) transfusion during aortic root replacement. Method: We reviewed patients undergoing aortic root replacement at our institution between March 2014 and April 2020. In total, 760 patients underwent aortic root replacement, of whom 442 (58%) received a perioperative RBC transfusion. Propensity score matching was used to account for baseline and operative differences resulting in 159 matched pairs. All-cause mortality was assessed with Kaplan-Meier curves. Data were obtained from our institutional Society of Thoracic Surgeons database and chart review. Results: After propensity score matching, the RBC-transfused and -nontransfused groups were similar for all preoperative characteristics. Cardiopulmonary bypass time, crossclamp time, and lowest operative temperature were similar between the transfused and nontransfused groups (standardized mean difference <0.05). RBC transfusion was associated with more frequent postoperative ventilation greater than 24 hours (36/159 [23%] vs 19/159 [12%]; P = .01), postoperative hemodialysis (9/159 [5.7%] vs 0/159 [0%]; P = .003), reoperation for mediastinal hemorrhage (9/159 [5.7%] vs 0/159 [0%]; P = .003), and longer intensive care unit and hospital length of stay (3 vs 2 days and 8 vs 6 days respectively; P < .001). Thirty-day operative mortality after propensity score matching was similar between the cohorts (1.9%; 3/159 vs 0%; P = .2), and 5-year survival was reduced in the RBC transfusion cohort (90.2% [95% confidence interval, 84.1%-96.7%] vs 97.1% [95% confidence interval, 92.3%-100%] P = .035). Conclusions: Aortic root replacement frequently requires RBC transfusion during and after the operation, but even after matching for observed preoperative and operative characteristics, RBC transfusion is associated with more frequent postoperative complications and reduced midterm survival.

Outcomes of Reoperative Aortic Root Replacement After Previous Acute Type A Dissection Repair.

Limited aortic root repair for acute type A dissection is associated with greater risk of proximal reoperations compared to full aortic root replacement. Surgical outcomes for patients undergoing reoperative root replacement after previous dissection repair are unknown. This study seeks to determine outcomes for these patients to further inform the debate surrounding optimal upfront management of the aortic root in acute dissection. Retrospective record review of all patients who underwent full aortic root replacement after a previous type A dissection repair operation at a tertiary academic referral center from 2004-2020 was performed. Among 57 cases of reoperative root replacement after type A repair, 35 cases included concomitant aortic arch replacements, and 21 cases involved coronary reconstruction (unilateral or bilateral modified Cabrol grafts). There were 3 acute postoperative strokes and 4 operative mortalities (composite 30-day and in-hospital deaths, 7.0%). Mid-term outcomes were equivalent for patients who required arch replacement compared to isolated proximal repairs (81.8% vs 80.6% estimated 5-year survival, median follow-up 5.53 years. Reoperative root replacement after index type A dissection repairs, including those with concomitant aortic arch replacement and/or coronary reconstruction is achievable with acceptable outcomes at an experienced aortic center.

Analysis of the revised heart allocation policy and the influence of increased mechanical circulatory support on survival.

OBJECTIVES: In 2018, the new United Network for Organ Sharing heart allocation policy took effect. This study evaluated waitlist mortality, mechanical circulatory support utilization, and its influence on posttransplant survival. METHODS: Two 12-month cohorts matched for time of year before and after the policy change were defined by inclusion criteria of first-time transplant recipients aged 18 years or older who were listed and underwent transplant during the same era. Student t test and Wilcoxon rank-sum test were used for mean and median differences, respectively. Categorical variables were compared using χ2 or Fisher exact test. Kaplan-Meier curves were used to characterize survival, including time-to-event analysis with the log-rank test. Fine-Gray modeling was used to characterize waitlist mortality. Cox proportional-hazard models were used for multivariate analysis. RESULTS: Waitlist mortality in the new era is significantly improved based on a competing-risks model (Gray test P = .0064). Unadjusted 180-day posttransplant mortality increased from 5.8% during the old era to 8.0% during the new (P = .0134). However, time-to-event analysis showed similar 180-day survival in both eras. After risk adjustment, the hazard ratio for posttransplant 180-day mortality during the new era was 1.18 (95% CI, 0.85-1.64; P = .333). The posttransplant 180-day mortality of the extracorporeal membrane oxygenation bridge-to-transplant subgroup improved from 28.6% in the old era to 8.4% in the new era (P = .0103; log-rank P = .0021). Patients with an intra-aortic balloon pump at the time of transplant had similar 180-day posttransplant mortality between eras (5.4% vs 7.0%; P = .4831). CONCLUSIONS: The United Network for Organ Sharing policy change is associated with reduced waitlist mortality and similar risk adjusted posttransplant 180-day mortality. The new era is also associated with improved 180-day survival in patients undergoing bridge to transplant with extracorporeal membrane oxygenation.

Surgical management of severe mitral annular calcification.

BACKGROUND: Surgical management of severe mitral annular calcification (MAC) presents a challenging problem for even the most experienced surgeons. Preoperative planning is the most effective strategy to mitigate risk in these scenarios. MAC alone should not disqualify a patient from consideration for mitral valve repair, although the presence of concurrent greater than moderate stenosis warrants consideration of mitral valve replacement. METHODS: While repair and replacement techniques for mitral regurgitation in the setting of MAC overlap with those used to repair a non-calcified mitral apparatus, there are unique considerations to the surgical conduct of these procedures. Specifically, this article describes techniques that may be employed when the severity of MAC precludes typical repair or replacement strategies. RESULTS: Between 2014 and 2021, 77 patients were operated on by a single surgeon for mitral valve disease complicated by severe MAC. Using the systematic approach described herein, 1-year mortality was 7.8% and overall mortality over a follow-up period extending 1 to 8 years was 9.1%. CONCLUSIONS: Despite the inherent challenges of mitral valve repair or replacement in the setting of severe MAC, a systematic approach beginning with preoperative planning, modification of annular suture placement, and techniques to mitigate severe complications have, in our experience, resulting in a reliable methodology for managing severe MAC with excellent outcomes.

Post-Transplant Extracorporeal Membrane Oxygenation for Severe Primary Graft Dysfunction to Support the Use of Marginal Donor Hearts.

Severe primary graft dysfunction (PGD) is the leading cause of early postoperative mortality following orthotopic heart transplantation (OHT). Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used as salvage therapy. This study aimed to evaluate the outcomes in adult OHT recipients who underwent VA-ECMO for severe PGD. We retrospectively reviewed 899 adult (≥18 years) patients who underwent primary OHT at our institution between 1997 and 2017. Recipients treated with VA-ECMO (19, 2.1%) exhibited a higher incidence of previous cardiac surgery (p = .0220), chronic obstructive pulmonary disease (p = .0352), and treatment with a calcium channel blocker (p = .0018) and amiodarone (p = .0148). Cardiopulmonary bypass (p = .0410) and aortic cross-clamp times (p = .0477) were longer in the VA-ECMO cohort and they were more likely to have received postoperative transfusion (p = .0013); intra-aortic balloon pump (IABP, p < .0001), and reoperation for bleeding or tamponade (p < .0001). The 30-day, 1-year, and overall survival after transplantation of non-ECMO patients were 95.9, 88.8, and 67.4%, respectively, compared to 73.7, 57.9, and 47.4%, respectively in the ECMO cohort. Fourteen (73.7%) of the ECMO patients were weaned after a median of 7 days following OHT (range: 1-12 days). Following OHT, VA-ECMO may be a useful salvage therapy for severe PGD and can potentially support the usage of marginal donor hearts.

Resection of a Giant Epithelioid Hemangioendothelioma Arising from the Superior Vena Cava.

Epithelioid hemangioendothelioma is a rare malignant vascular sarcoma. Here we present a patient with a very large tumor arising from the superior vena cava, in whom a resection with negative margins was accomplished using venovenous bypass and bovine pericardial patch reconstruction of the superior vena cava.

A novel cross-species model of Barlow's disease to biomechanically analyze repair techniques in an ex vivo left heart simulator.

OBJECTIVE: Barlow's disease remains challenging to repair, given the complex valvular morphology and lack of quantitative data to compare techniques. Although there have been recent strides in ex vivo evaluation of cardiac mechanics, to 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. METHODS: 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 bileaflet 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 < .001) and strain gauge analysis revealed lower primary chordae forces (0.51 ± 0.17 vs 0.10 ± 0.05 N, P < .001). In addition, the maximum rate of change of force was significantly lower postrepair for both primary (30.80 ± 11.38 vs 8.59 ± 4.83 N/s, P < .001) and secondary chordae (33.52 ± 10.59 vs 19.07 ± 7.00 N/s, P = .006). CONCLUSIONS: This study provides insight into the biomechanics of Barlow's disease, including sharply fluctuating force profiles experienced by elongated chordae prerepair, as well as restoration of primary chordae forces postrepair. Our disease model facilitates further in-depth analyses to optimize the repair of Barlow's disease.

Intracardiac paragangliomas: surgical approach and perioperative management.

Intracardiac paragangliomas most commonly arise from the left atrium and are often infiltrative and densely adherent to surrounding structures. Given their rarity, only scattered reports exist in the literature and standardized perioperative and surgical management is not well established. We describe a case of a 60-year-old woman with a mildly functioning intracardiac paraganglioma in which division of the superior vena cava improved exposure and enabled a complex limited resection. Further, we provide an overview of the diagnostic workup, perioperative medical management, surgical approach, and surveillance strategy in patients with these challenging tumors.

Ex Vivo Analysis of a Porcine Bicuspid Aortic Valve and Aneurysm Disease Model.

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.

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.

Signalosome-Regulated Serum Response Factor Phosphorylation Determining Myocyte Growth in Width Versus Length as a Therapeutic Target for Heart Failure.

BACKGROUND: Concentric and eccentric cardiac hypertrophy are associated with pressure and volume overload, respectively, in cardiovascular disease both conferring an increased risk of heart failure. These contrasting forms of hypertrophy are characterized by asymmetrical growth of the cardiac myocyte in mainly width or length, respectively. The molecular mechanisms determining myocyte preferential growth in width versus length remain poorly understood. Identification of the mechanisms governing asymmetrical myocyte growth could provide new therapeutic targets for the prevention or treatment of heart failure. METHODS: Primary adult rat ventricular myocytes, adeno-associated virus (AAV)-mediated gene delivery in mice, and human tissue samples were used to define a regulatory pathway controlling pathological myocyte hypertrophy. Chromatin immunoprecipitation assays with sequencing and precision nuclear run-on sequencing were used to define a transcriptional mechanism. RESULTS: We report that asymmetrical cardiac myocyte hypertrophy is modulated by SRF (serum response factor) phosphorylation, constituting an epigenomic switch balancing the growth in width versus length of adult ventricular myocytes in vitro and in vivo. SRF Ser103 phosphorylation is bidirectionally regulated by RSK3 (p90 ribosomal S6 kinase type 3) and PP2A (protein phosphatase 2A) at signalosomes organized by the scaffold protein mAKAPß (muscle A-kinase anchoring protein ß), such that increased SRF phosphorylation activates AP-1 (activator protein-1)-dependent enhancers that direct myocyte growth in width. AAV are used to express in vivo mAKAPß-derived RSK3 and PP2A anchoring disruptor peptides that block the association of the enzymes with the mAKAPß scaffold. Inhibition of RSK3 signaling prevents concentric cardiac remodeling induced by pressure overload, while inhibition of PP2A signaling prevents eccentric cardiac remodeling induced by myocardial infarction, in each case improving cardiac function. SRF Ser103 phosphorylation is significantly decreased in dilated human hearts, supporting the notion that modulation of the mAKAPß-SRF signalosome could be a new therapeutic approach for human heart failure. CONCLUSIONS: We have identified a new molecular switch, namely mAKAPß signalosome-regulated SRF phosphorylation, that controls a transcriptional program responsible for modulating changes in cardiac myocyte morphology that occur secondary to pathological stressors. Complementary AAV-based gene therapies constitute rationally-designed strategies for a new translational modality for heart failure.

Impact of Surgical Approach in Double Lung Transplantation: Median Sternotomy vs Clamshell Thoracotomy.

BACKGROUND: Double lung transplantation (DLT) remains the gold standard for end-stage lung disease. Although DLT was historically performed via clamshell thoracotomy, recently the median sternotomy has emerged as a viable alternative. As the ideal surgical approach remains unclear, the aim of our study was to compare the short- and long-term outcomes of these 2 surgical approaches in DLT. METHODS: We retrospectively reviewed 192 consecutive adult patients who underwent primary DLT at our institution between 2012 and 2017 (sternotomy, n = 147; clamshell, n = 45). The impact of each surgical approach on post-transplant morbidity was investigated, and the overall survival probability analyses were performed. RESULTS: There were no significant differences in recipients' baseline and donors' characteristics and bilateral allograft ischemic time. Freedom from primary graft dysfunction, acute rejection episodes, postoperative prolonged ventilator support, tracheostomy, postoperative stroke, and airway dehiscence were comparable between these 2 groups. The duration of cardiopulmonary bypass and operative time were significantly longer in the clamshell thoracotomy group. Postoperative extracorporeal membrane oxygenation usage tended to be more frequent in the clamshell thoracotomy group than the median sternotomy group, despite no statistical significance. Length of hospital and intensive care unit stay were not influenced by the type of incision. There was no significant difference in overall survival between these 2 procedure groups (P = .61, log-rank test). CONCLUSIONS: The median sternotomy approach in DLT decreases operative time and more importantly leads to a shorter duration of cardiopulmonary bypass. The type of surgical approach did not show any statistically significant impact on adult DLT recipients' morbidity and survival.

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.

Surgical excision of a free floating ascending aortic thrombus.

BACKGROUND: A 73-year-old female presented with leg claudication and chest pain. A mobile mass in the ascending aorta was found. RESULTS: The mass was removed through a transverse aortotomy on circulatory arrest via sternotomy. CONCLUSION: Free-floating ascending aortic thrombus is a rare source of peripheral embolization. We advocate for emergent surgical resection to prevent further embolization and stroke.

Surgical Management for Aortoesophageal Fistula After Endovascular Aortic Repair.

This case demonstrates successful surgical management of a 6-cm-long aortoesophageal fistula from an infected stent graft. A 69-year-old woman with a penetrating descending thoracic aortic ulcer underwent endovascular aortic repair. Two weeks later, she presented with nausea and melena, and she was found to have an infected stent graft on imaging. She underwent a two-stage procedure encompassing aortic arch debranching and extra-anatomic aortic bypass in stage 1, and stent graft resection, primary esophageal repair, intercostal and omental flap, and jejunostomy tube placement in stage 2. She was discharged 1 month later and is doing well 1.5 years after the operation.

A modified implantation technique for temporary right ventricular assist device: Enabling ambulation and less invasive decannulation.

This report describes our unique temporary right ventricular assist device (RVAD) implantation technique, which enables early mobilization even during biventricular support and subsequent less invasive RVAD removal without needing resternotomy upon recovery.