Intimomedial tears of the aorta heal by smooth muscle cell-mediated fibrosis without atherosclerosis.

BACKGROUNDDisease of the aorta varies from atherosclerosis to aneurysms, with complications including rupture, dissection, and poorly characterized limited tears. We studied limited tears without any mural hematoma, termed intimomedial tears, to gain insight into aortic vulnerability to excessive wall stresses. Our premise is that minimal injuries in aortas with sufficient medial resilience to prevent tear progression correspond to initial mechanisms leading to complete structural failure in aortas with significantly compromised medial resilience.METHODSIntimomedial tears were macroscopically identified in 9 of 108 ascending aortas after surgery and analyzed by histology and immunofluorescence confocal microscopy.RESULTSNonhemorrhagic, nonatheromatous tears correlated with advanced aneurysmal disease and most lacked distinctive symptoms or radiological signs. Tears traversed the intima and part of the subjacent media, while the resultant defects were partially or completely filled with neointima characterized by differentiated smooth muscle cells, scattered leukocytes, dense fibrosis, and absent elastic laminae despite tropoelastin synthesis. Healed lesions contained organized fibrin at tear edges without evidence of plasma and erythrocyte extravasation or lipid accumulation.CONCLUSIONThese findings suggest a multiphasic model of aortic wall failure in which primary lesions of intimomedial tears either heal if the media is sufficiently resilient or progress as dissection or rupture by medial delamination and tear completion, respectively. Moreover, mural incorporation of thrombus and cellular responses to injury, two historically important concepts in atheroma pathogenesis, contribute to vessel wall repair with adequate conduit function, but even together are not sufficient to induce atherosclerosis.FUNDINGNIH (R01-HL146723, R01-HL168473) and Yale Department of Surgery.

Living in disadvantaged neighborhoods linked to less intervention for severe aortic stenosis.

To investigate the association between area deprivation index (ADI) and aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Patients aged 40-95 years with severe AS confirmed by echocardiography were included. The 9-digit zip code of patient residence address was used to identify the ADI ranking, based on which patients were divided into 5 groups (with Group E being most deprived). The rates of AV intervention were compared among 5 groups using competing risks analysis, with death as a competing event. We included 1751 patients with severe AS from 2013 to 2018 followed for a median 2.8 (interquartile range, 1.5-4.8) years. The more distressed ADI groups tended to be younger (P = 0.002), female (P < 0.001), and of African American race (P < 0.001), have higher presentation of sepsis (P = 0.031), arrhythmia (P = 0.022), less likely to have previous diagnosis of AS (P < 0.001); and were less likely to undergo AVR (52.5% vs 46.9% vs 46.1% vs 48.9% vs 39.7%, P = 0.023). Using competing risk analysis, the highest ADI group (E) were the least and the lowest ADI group (A) the most likely to undergo AVR (Gray's test, P = 0.025). The association between ADI ranking and AVR rates was influenced by sex and race. Within group analysis, there was significant association between race and AVR (Gray's test, P < 0.001), and between sex and AVR (Gray's test, P < 0.001). Patients with severe AS living in more deprived neighborhoods were less likely to undergo aortic valve interventions, which was influenced by female gender, and African American race.

Aortic remodeling following hybrid arch repair with zone 0 to 5 thoracic endovascular aortic repairs for complex arch and descending thoracic aortic pathologies.

Objective: For high-risk patients with aortic arch pathology, hybrid aortic arch repair with simultaneous or staged thoracic endovascular repair of the descending aorta may be a viable alternative to open repair. However, data on postintervention aortic remodeling remain limited. We report the short-term outcomes of remodeling of the thoracoabdominal aorta after hybrid arch repair + thoracic endovascular repair. Methods: All patients undergoing hybrid arch repair with planned zones 0 to 5 thoracic endovascular repair from January 2020 to March 2022 were retrospectively reviewed. Computed tomography angiography scans preoperatively, after hybrid aortic arch repair, and on long-term follow-up were analyzed for thoracoabdominal aorta remodeling. Mean change in aortic true luminal diameter and full luminal diameter was calculated at every level, and paired-samples t test was used to compare means. Results: Of 39 patients, 38 had follow-up data at a mean duration of 14.9 months. There were a total of 3 (7.7%) deaths, 0 (0.0%) strokes, and 0 (0.0%) paralysis. For the 35 patients undergoing thoracic endovascular repair for aortic dissection, at follow-up, there was a significant increase in the mean true luminal diameter at each level (P < .05), except at the aortic bifurcation and common iliac arteries. The largest increase in mean true luminal diameter (P < .01) was observed at the level of the left inferior pulmonary vein (mean difference +13.22 mm, 95% CI, 10.38-16.07), tracheal carina (mean difference +13.06 mm, 95% CI, 10.05-16.07), and inferior left atrium (mean difference +11.19 mm, 95% CI, 7.84-14.53). Conclusions: Hybrid arch repair with zones 0 to 5 leads to improved true lumen augmentation in zones 0 to 8 with complete false lumen thrombosis down to zone 5 at short-term follow-up. Zones 9 to 11, if involved, may require adjunctive treatment strategies for total aortic remodeling and complete false lumen obliteration.

Circulating T cell specific extracellular vesicle profiles in cardiac allograft acute cellular rejection.

There is a critical need for biomarkers of acute cellular rejection (ACR) in organ transplantation. We hypothesized that ACR leads to changes in donor-reactive T cell small extracellular vesicle (sEV) profiles in transplant recipient circulation that match the kinetics of alloreactive T cell activation. In rodent heart transplantation, circulating T cell sEV quantities (P < .0001) and their protein and mRNA cargoes showed time-specific expression of alloreactive and regulatory markers heralding early ACR in allogeneic transplant recipients but not in syngeneic transplant recipients. Next generation sequencing of their microRNA cargoes identified novel candidate biomarkers of ACR, which were validated by stem loop quantitative reverse transcription polymerase chain reaction (n = 10). Circulating T cell sEVs enriched from allogeneic transplant recipients mediated targeted cytotoxicity of donor cardiomyocytes by apoptosis assay (P < .0001). Translation of the concept and EV methodologies to clinical heart transplantation demonstrated similar upregulation of circulating T cell sEV profiles at time points of grade 2 ACR (n = 3 patients). Furthermore, T cell receptor sequencing of T cell sEV mRNA cargo demonstrated expression of T cell clones with intact complementarity determining region 3 signals. These data support the diagnostic potential of T cell sEVs as noninvasive biomarker of ACR and suggest their potential functional roles.

Intramyocardial cell-based therapy with Lomecel-B during bidirectional cavopulmonary anastomosis for hypoplastic left heart syndrome: the ELPIS phase I trial.

Aims: Hypoplastic left heart syndrome (HLHS) survival relies on surgical reconstruction of the right ventricle (RV) to provide systemic circulation. This substantially increases the RV load, wall stress, maladaptive remodelling, and dysfunction, which in turn increases the risk of death or transplantation. Methods and results: We conducted a phase 1 open-label multicentre trial to assess the safety and feasibility of Lomecel-B as an adjunct to second-stage HLHS surgical palliation. Lomecel-B, an investigational cell therapy consisting of allogeneic medicinal signalling cells (MSCs), was delivered via intramyocardial injections. The primary endpoint was safety, and measures of RV function for potential efficacy were obtained. Ten patients were treated. None experienced major adverse cardiac events. All were alive and transplant-free at 1-year post-treatment, and experienced growth comparable to healthy historical data. Cardiac magnetic resonance imaging (CMR) suggested improved tricuspid regurgitant fraction (TR RF) via qualitative rater assessment, and via significant quantitative improvements from baseline at 6 and 12 months post-treatment (P < 0.05). Global longitudinal strain (GLS) and RV ejection fraction (EF) showed no declines. To understand potential mechanisms of action, circulating exosomes from intramyocardially transplanted MSCs were examined. Computational modelling identified 54 MSC-specific exosome ribonucleic acids (RNAs) corresponding to changes in TR RF, including miR-215-3p, miR-374b-3p, and RNAs related to cell metabolism and MAPK signalling. Conclusion: Intramyocardially delivered Lomecel-B appears safe in HLHS patients and may favourably affect RV performance. Circulating exosomes of transplanted MSC-specific provide novel insight into bioactivity. Conduct of a controlled phase trial is warranted and is underway.Trial registration number NCT03525418.

Trans-sternotomy, snare-assisted thoracic endovascular aortic repair for redirection of a migrated elephant trunk.

The two-stage elephant trunk (ET) and thoracic endovascular aortic repair technique for type A and B aortic dissection can result in complications between the two stages. We have presented the case of a patient with an acute-on-chronic type B aortic dissection complicated by ET kinking and migration into the false lumen. We used a hybrid approach consisting of a first stage (retrograde thoracic endovascular aortic repair) and a second stage ("body floss" with antegrade thoracic endovascular aortic repair) to successfully reposition the ET back into the true lumen.

Extracorporeal membrane oxygenator as a bridge to definitive treatment in patients with persistent infective endocarditis.

Considering the worsening opioid epidemic, complicated infective endocarditis (IE) secondary to intravenous drug use (IVDU) that fails medical management is increasingly common. We present a 31-year-old patient post tricuspid valve replacement who relapsed with recurrent IE and secondary complications of severe tricuspid stenosis and regurgitation, ventricular septal defect (VSD), pulmonary emboli, right-sided heart failure with severe hepatic congestion, and cardiogenic shock. Despite maximal medical management, the patient remained in septic and cardiogenic shock with a potential disposition to hospice care. Upon consulting cardiothoracic surgery, she underwent a first-stage valvectomy with central Extracorporeal Membrane Oxygenation (ECMO) as a bridge to definitive treatment. After clearance of infection, she underwent a second-stage valve replacement, VSD repair, and final ECMO decannulation. Our case alludes to ECMO as a potential bridge for patients with complicated infective endocarditis who fail medical management and are high-risk candidates for immediate definitive surgical management.

Management of Thoracic Aortic Dissection.

This JAMA Clinical Guidelines Synopsis summarizes the 2021 guidelines from the American Association for Thoracic Surgery and the Society of Thoracic Surgeons on management of type A and type B thoracic aortic dissection.

TAVR explant with aortic root replacement using a homograft for an aortic rupture.

This case report describes the explantation of an Evolut PRO valve 9 months after implantation in a 69-year-old male presenting with an aortic rupture adjacent to the stent frame of the prosthesis. Imaging was consistent with aortic sinus pseudoaneurysm and a large haemopericardium. Degeneration of the aortic root compounded by the transcatheter prosthesis in addition to the aortic rupture required replacement of the aortic root. The complexity of the procedure also required a modified Cabrol extension of the left coronary button and reconstruction of the left coronary button with bovine pericardium. We describe the technical challenges posed by the self-expanding transcatheter aortic valve prosthesis and tips and tricks to circumvent these challenges.

Long-term outcomes of aortic root operations in the United States among Medicare beneficiaries.

OBJECTIVE: The best method of aortic root repair in older patients remains unknown given a lack of comparative effectiveness of long-term outcomes data. The objective of this study was to compare long-term outcomes of different surgical approaches for aortic root repair in Medicare patients using The Society of Thoracic Surgeons Adult Cardiac Surgery Database-Centers for Medicare & Medicaid Services-linked data. METHODS: A retrospective cohort study was performed by querying the Society of Thoracic Surgeons Adult Cardiac Surgery Database for patients aged 65 years or more who underwent elective aortic root repair with or without aortic valve replacement. Primary long-term end points were mortality, any stroke, and aortic valve reintervention. Short-term outcomes and long-term survival were compared among each root repair strategy. Additional risk factors for mortality after aortic root repair were assessed with a multivariable Cox proportional hazards model. RESULTS: A total of 4173 patients aged 65 years or more underwent elective aortic root repair. Patients were stratified by operative strategy: mechanical Bentall, stented bioprosthetic Bentall, stentless bioprosthetic Bentall, or valve-sparing root replacement. Mean follow-up was 5.0 (±4.6) years. Relative to mechanical Bentall, stented bioprosthetic Bentall (adjusted hazard ratio, 0.80; confidence interval, 0.66-0.97) and stentless bioprosthetic Bentall (adjusted hazard ratio, 0.70; confidence interval, 0.59-0.84) were associated with better long-term survival. In addition, stentless bioprosthetic Bentall (adjusted hazard ratio, 0.64; confidence interval, 0.47-0.80) and valve-sparing root replacement (adjusted hazard ratio, 0.51; confidence interval, 0.29-0.90) were associated with lower long-term risk of stroke. Aortic valve reintervention risk was 2-fold higher after valve-sparing root replacement compared with other operative strategies. CONCLUSIONS: In the Medicare population, there was poorer late survival and greater late stroke risk for patients undergoing mechanical Bentall and a higher rate of reintervention for valve-sparing root replacement. Bioprosthetic Bentall may be the procedure of choice in older patients undergoing aortic root repair, particularly in the era of transcatheter aortic valve replacement.

Intraoperative Finding of Anomalous Circumflex Artery Origin in the Dissected Right Coronary Ostium.

Anomalous origin of the left circumflex artery is a rare anatomical variant that may present a unique challenge in emergent aortic surgery.

Variability in surveillance practice for patients with diagnosis of bicuspid aortic valve syndrome.

In patients with bicuspid aortic valves, guidelines call for regular follow-up to monitor disease progression and guide intervention. We aimed to evaluate how closely these recommendations are followed at a tertiary care center. Among 48,504 patients who received echocardiograms (2013-2018) at a tertiary care center, 245 patients were identified to have bicuspid aortic valve. Bivariate analyses compared characteristics between patients who did and did not receive follow-up by a cardiovascular specialist. During a median follow-up of 3.5 ± 2.2 years (mean age 55.2 ± 15.6 years, 30.2% female), 72.7% of patients had at least one visit with a cardiovascular specialist after diagnosis of bicuspid aortic valve. These patients had a higher proportion of surveillance by echocardiogram (78.7% vs. 34.3%, p < .0001), CT or MRI (41.0% vs. 3.0%, p < .0001), and were more likely to undergo surgery. Patients with moderate-severe valvular or aortic pathology were not more likely to be followed by a specialist or receive follow-up echocardiograms. Follow-up care for patients with bicuspid aortic valve was highly variable, and surveillance imaging was sparse despite guidelines. There is an urgent need for mechanisms to monitor this population with increased risk of progressive valvulopathy and aortopathy.

Direct relationship between transvalvular velocity and cardiac dysfunction, morbidity, and mortality in patients with aortic stenosis.

OBJECTIVE: Current guidelines recommend intervention in subjects with severe symptomatic aortic stenosis (AS), even though any degree of AS is associated with a higher risk of mortality. We investigated the association between the degree of AS, delineated by transvalvular flow velocity, and patient morbidity and mortality. METHODS: Medically managed patients aged 40-95 years with maximum flow velocity (Vmax ) by echocardiography between 2013 and 2018 were stratified into five groups (A-E) based on the 75th, 90th, 97.5th, and the 99th percentiles of Vmax distribution. Patient characteristics, cardiac structural changes, and end-organ disease were compared using Kruskal-Wallis and Cochran-Armitage tests. Mortality over a median of 2.8 (1.52-4.8) years was compared using Kaplan-Meier curves and risk estimates were derived from the Cox model. RESULTS: The Vmax was reported in 37,131 patients. There was a steady increase (from Group A towards E) in age, Caucasian race, structural cardiac changes, end-organ morbidities, and all-cause mortality. In reference to Group A, there as an increased risk of mortality in Groups B (hazard ratio [HR] = 1.3; confidence interval [CI]: 1.2-1.35; p < .0001), C (HR = 1.5; CI: 1.4-1.6; p < .0001), and D (HR = 1.8; CI: 1.6-2; p < .0001), with an exponential increase in Group E (HR = 2.5; CI: 2.2-2.8; p < .0001). CONCLUSIONS: A direct, strong correlation exists between the degree of AS and cardiac structural changes and mortality. Patients with Vmax ≥ 97.5th percentile (≥3.2 m/s) might benefit from early intervention.

Comprehensive review of hybrid aortic arch repair with focus on zone 0 TEVAR and our institutional experience.

Even with increasing operator experience and a better understanding of the disease and the operation, intervention for aortic arch pathologies continues to struggle with relatively higher mortality, reintervention, and neurologic complications. The hybrid aortic arch repair was introduced to simplify the procedure and improve the outcome. With recent industry-driven advances, hybrid repairs are not only offered to poor surgical candidates but have become mainstream. This review discusses the evolution of hybrid repair, terminology pertinent to this technique, and results. In addition, we aim to provide a pervasive review of hybrid aortic arch repairs with reference to relevant literature for a detailed understanding. We have also discussed our institutional experience with hybrid repairs.

Long-term risk of arch complications in Loeys Dietz syndrome patients undergoing proximal ascending aortic replacement.

PURPOSE: Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder. In LDS patients with normal arch morphology, whether the arch should be prophylactically replaced at the time of proximal aortic replacement remains unknown. We evaluated the risk of long-term arch complications in genetically confirmed LDS patients who underwent proximal ascending aortic replacement. METHODS: We retrospectively reviewed the records of patients with LDS who have been followed at our institution between 1994 and 2020. Patients were only included if whole exome genetic testing confirmed a mutation in an LDS-causing gene (TGFBR1, TGFBR2, SMAD3, TGFB2, or TGFB3). Mutations were categorized as pathogenic, benign, or of unknown significance. We collected demographic information, aortic dimensions, comorbidities, mortality, and operative course from patients' charts. Descriptive statistics and freedom from reoperation plots were generated. RESULTS: Of the 18 patients with a mutation in an LDS-causing gene, 15 had known pathogenic variants, two had mutations of unknown significance, and one had a benign genetic variant. For the 15 patients with confirmed pathogenic variants of LDS the median follow-up duration was 5 years (interquartile range [IQR]: 4-8). Eleven patients underwent ascending aortic replacements (AAR) ± aortic valve replacement. Two patients required an additional operation; one required arch and staged elephant trunk for a dissection 18 years post-AAR and the other patient required an isolated descending aortic replacement for dissection 5 years post-AAR. Among patients who underwent surgery, the median ascending aortic diameter at intervention was 5.0 cm (IQR: 4.3-5.3). There was no surgical or late follow-up mortality observed for any of the 18 patients in the study. CONCLUSION: LDS patients who underwent proximal aortic replacement appeared to have low long-term risk of arch complications. While our study is somewhat limited by its sample size and follow-up duration, it suggests that routine prophylactic total arch replacement may not be warranted in LDS patients with nonaneurysmal aortic arches.

Screening Tool to Identify Patients with Advanced Aortic Valve Stenosis.

(1) Background: The clinical burden of aortic stenosis (AS) remains high in Western countries. Yet, there are no screening algorithms for this condition. We developed a risk prediction model to guide targeted screening for patients with AS. (2) Methods: We performed a cross-sectional analysis of all echocardiographic studies performed between 2013 and 2018 at a tertiary academic care center. We included reports of unique patients aged from 40 to 95 years. A logistic regression model was fitted for the risk of moderate and severe AS, with readily available demographics and comorbidity variables. Model performance was assessed by the C-index, and its calibration was judged by a calibration plot. (3) Results: Among the 38,788 reports yielded by inclusion criteria, there were 4200 (10.8%) patients with ≥moderate AS. The multivariable model demonstrated multiple variables to be associated with AS, including age, male gender, Caucasian race, Body Mass Index ≥ 30, and cardiovascular comorbidities and medications. C-statistics of the model was 0.77 and was well calibrated according to the calibration plot. An integer point system was developed to calculate the predicted risk of ≥moderate AS, which ranged from 0.0002 to 0.7711. The lower 20% of risk was approximately 0.15 (corresponds to a score of 252), while the upper 20% of risk was about 0.60 (corresponds to a score of 332 points). (4) Conclusions: We developed a risk prediction model to predict patients' risk of having ≥moderate AS based on demographic and clinical variables from a large population cohort. This tool may guide targeted screening for patients with advanced AS in the general population.

One and Five-Year Mortality Risk Prediction in Patients with Moderate and Severe Aortic Stenosis.

(1) Background: Our goal was to develop a risk prediction model for mortality in patients with moderate and severe aortic stenosis (AS). (2) Methods: All patients aged 40−95 years, with echocardiographic evidence of moderate and severe AS at a single institution, were studied over a median of 2.8 (1.5−4.8) years, between 2013−2018. Patient characteristics and mortality were compared using Chi-squares, t-tests, and Kaplan−Meier (KM) curves, as appropriate. The risk calculation for mortality was derived using the Cox proportional hazards model. A risk score was calculated for each parameter, and the total sum of scores predicted the individualized risks of 1-and 5-year mortality. (3) Results: A total of 1991 patients with severe and 2212 with moderate AS were included. Severe AS patients were older, had a lower ejection fraction %, were more likely to be Caucasian, and had lower rates of obesity and smoking, but had higher rates of cardiac comorbidities and AVR (49.3% vs. 2.8%, p < 0.0001). The unadjusted overall mortality was 41.7% vs. 41%, p = 0.6530, and was not different using KM curves (log rank, p = 0.0853). The models included only patients with complete follow-up (3966 in the 1-year, and 816 in the 5-year model) and included 13 variables related to patient characteristics, degree of AS, and AVR. The C-statistic was 0.75 and 0.72 for the 1-year and the 5-year models, respectively. (4) Conclusions: Patients with moderate and severe AS experience high morbidity and mortality. The usage of a risk prediction model may provide guidance for clinical decision making in complex patients.

Institution representation in publications reporting mitral valve repair durability: A scoping review.

BACKGROUND: Mitral valve repair durability currently plays a key role in operative decision making and in defining optimal surgical practice. However, mitral valve durability outcomes measures are not captured by national registries and limited to centers that publish their outcomes. In this study, we aim to describe the scope of institutions represented by reports describing durability outcomes after mitral valve repair within the contemporary literature. METHODS AND RESULTS: A scoping review of the literature was performed to extract abstracts potentially reporting mitral valve operation outcomes published between 2000-2019. 370 full text articles reporting mitral valve durability outcomes by either reoperation rate or rate of recurrent mitral regurgitation met criteria for analysis. Study characteristics including case volume, country and institution of origin, and surgeon volume were extracted and used to calculate the proportion of total cases in the top 3, 5, and 10 represented countries and institutions by the sum of reported mitral valve repairs described. The top 5 of 21 countries represented 78.9% of the mitral valve repair cases described. The top 3 most represented institutions described 20,120 (37.3%) of all mitral valve repairs in 58 (33.9%) single-center studies. CONCLUSION: Published mitral valve repair durability data must be interpreted with caution when used to derive policies and practice recommendations that govern the cardiovascular community at large.