Wild-type Transthyretin Amyloid Deposition in an Ascending Aortic Aneurysm.

Amyloid deposition in aortic tissue is associated with increased stiffness. We report a patient with ascending aortic aneurysm and chronic abdominal aortic dissection who had significant wild-type transthyretin amyloid deposition on surgical pathology. The patient did not have cardiac involvement on further workup.

Long-term outcomes after recurrent acute thoracic aortic dissection: Insights from the International Registry of Aortic Dissection.

OBJECTIVE: With an aging population and advancements in imaging, recurrence of thoracic aortic dissection is becoming more common. METHODS: All patients enrolled in the International Registry of Aortic Dissection from 1996 to 2023 with type A and type B acute aortic dissection were identified. Among them, initial dissection and recurrent dissection were discerned. The study period was categorized into 3 eras: historic era, 1996 to 2005; middle era, 2006 to 2015; most recent era, 2016 to 2023. Propensity score matching was applied between initial dissection and recurrent dissection. Outcome of interests included long-term survival and cumulative incidence of major aortic events defined by the composite of reintervention, aortic rupture, and new dissection. RESULTS: The proportion of recurrent dissection increased from 5.9% in the historic era to 8.0% in the most recent era in the entire dissection cohort. In patients with type A dissection, propensity score matching between initial dissection and recurrent dissection yielded 326 matched pairs. Kaplan-Meier curves showed similar long-term survival between the 2 groups. However, the cumulative incidence of major aortic events was significantly higher in the recurrent dissection group (40.3% ± 6.2% vs 17.8% ± 5.1% at 4 years in the initial dissection group, P = .02). For type B dissection, 316 matched pairs were observed after propensity score matching. Long-term survival and the incidence of major aortic events were equivalent between the 2 groups. CONCLUSIONS: The case volume of recurrent dissection or the ability to detect recurrent dissection has increased over time. Acute type A recurrent dissection was associated with a higher risk of major aortic events than initial dissection. Further judicious follow-up may be crucial after type A recurrent dissection.

Maternal Cardiovascular Health Post-Dobbs.

Maternal Cardiovascular Health Post-DobbsPregnancy is associated with increasing morbidity and mortality in the United States. In the post-Dobbs era, many pregnant patients at highest risk no longer have access to abortion, which has been a crucial component of standard medical care.

Twenty-five years of observations from the International Registry of Acute Aortic Dissection (IRAD) and its impact on the cardiovascular scientific community.

OBJECTIVE: The International Registry of Acute Aortic Dissection (IRAD) celebrated its 25th anniversary in January 2021. This study evaluated IRAD's role in promoting the understanding and management of acute aortic dissection (AD) over these years. METHODS: IRAD studies were identified, analyzed, and ranked according to their citations per year (c/y) to determine the most-cited IRAD studies and topics. A systematic search of the literature identified cardiovascular guidelines on the diagnosis and management of acute AD. Consequently, IRAD's presence and impact were quantified using these documents. RESULTS: Ninety-seven IRAD studies were identified, of which 82 obtained more than 10 cumulative citations. The median c/y index was 7.33 (25th-75th percentile, 4.01-16.65). Forty-two studies had a greater than median c/y index and were considered most impactful. Of these studies, most investigated both type A and type B AD (n = 17, 40.5%) and short-term outcomes (n = 26, 61.9%). Nineteen guideline documents were identified from 26 cardiovascular societies located in Northern America, Europe, and Japan. Sixty-nine IRAD studies were cited by these guidelines, including 38 of the 42 most-impactful IRAD studies. Among them, partial thrombosis of the false lumen as a predictor of postdischarge mortality and aortic diameters as a predictor of type A occurrence were determined as most-impactful specific IRAD topics by their c/y index. CONCLUSIONS: IRAD has had and continues to have an important role in providing observations, credible knowledge, and research questions to improve the outcomes of patients with acute AD.

2022 ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. STRUCTURE: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.

Prophylactic Surgery for Thoracic Aortic Aneurysm: Asking Family for Help.

A 68-year-old man presented for evaluation of a 5.0-cm asymptomatic ascending aortic aneurysm. He was managed medically until a family member was also diagnosed with a thoracic aortic aneurysm. His aneurysm was, therefore, likely to be genetically predisposed, and he underwent early prophylactic ascending aorta replacement. (Level of Difficulty: Beginner.).

Infectious Aortitis of Thoracic Aortic Aneurysm From Clostridium Septicum.

A 71-year-old male presented with 1-day history of back pain. Imaging displayed an enlarging thoracic aortic aneurysm with gas in the aortic wall. Blood cultures grew Clostridium septicum. He underwent resection, debridement, and in situ aortic replacement with a rifampin-soaked graft under deep hypothermic circulatory arrest. His recovery was uncomplicated. (Level of Difficulty: Beginner.).

Development of a Prediction Model for Ascending Aortic Diameter Among Asymptomatic Individuals.

Importance: Ascending thoracic aortic disease is an important cause of sudden death in the US, yet most aortic aneurysms are identified incidentally. Objective: To develop and validate a clinical score to estimate ascending aortic diameter. Design, Setting, and Participants: Using an ongoing magnetic resonance imaging substudy of the UK Biobank cohort study, which had enrolled participants from 2006 through 2010, score derivation was performed in 30 018 participants and internal validation in an additional 6681. External validation was performed in 1367 participants from the Framingham Heart Study (FHS) offspring cohort who had undergone computed tomography from 2002 through 2005, and in 50 768 individuals who had undergone transthoracic echocardiography in the Community Care Cohort Project, a retrospective hospital-based cohort of longitudinal primary care patients in the Mass General Brigham (MGB) network between 2001-2018. Exposures: Demographic and clinical variables (11 covariates that would not independently prompt thoracic imaging). Main Outcomes and Measures: Ascending aortic diameter was modeled with hierarchical group least absolute shrinkage and selection operator (LASSO) regression. Correlation between estimated and measured diameter and performance for identifying diameter 4.0 cm or greater were assessed. Results: The 30 018-participant training cohort (52% women), were a median age of 65.1 years (IQR, 58.6-70.6 years). The mean (SD) ascending aortic diameter was 3.04 (0.31) cm for women and 3.32 (0.34) cm for men. A score to estimate ascending aortic diameter explained 28.2% of the variance in aortic diameter in the UK Biobank validation cohort (95% CI, 26.4%-30.0%), 30.8% in the FHS cohort (95% CI, 26.8%-34.9%), and 32.6% in the MGB cohort (95% CI, 31.9%-33.2%). For detecting individuals with an ascending aortic diameter of 4 cm or greater, the score had an area under the receiver operator characteristic curve of 0.770 (95% CI, 0.737-0.803) in the UK Biobank, 0.813 (95% CI, 0.772-0.854) in the FHS, and 0.766 (95% CI, 0.757-0.774) in the MGB cohorts, although the model significantly overestimated or underestimated aortic diameter in external validation. Using a fixed-score threshold of 3.537, 9.7 people in UK Biobank, 1.8 in the FHS, and 4.6 in the MGB cohorts would need imaging to confirm 1 individual with an ascending aortic diameter of 4 cm or greater. The sensitivity at that threshold was 8.9% in the UK Biobank, 11.3% in the FHS, and 18.8% in the MGB cohorts, with specificities of 98.1%, 99.2%, and 96.2%, respectively. Conclusions and Relevance: A prediction model based on common clinically available data was derived and validated to predict ascending aortic diameter. Further research is needed to optimize the prediction model and to determine whether its use is associated with improved outcomes.

2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. Structure: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.

Survival after operative repair of acute type A aortic dissection varies according to the presence and type of preoperative malperfusion.

OBJECTIVE: Approximately one-quarter of patients with acute type A aortic dissection (TAAD) present with concomitant malperfusion of coronary arteries, mesenteric circulation, lower extremities, kidneys, brain, and/or coma. It is generally accepted that TAAD patients who present with malperfusion experience higher mortality rates than patients without, although how specific malperfusion syndromes, alone or in combination, affect mortality is not well described. METHODS: The International Registry of Acute Aortic Dissection database was queried for patients who underwent surgical repair of TAAD. Patients were stratified according to the presence/absence of malperfusion at presentation. Multivariable logistic regression was used to evaluate in-hospital mortality according to malperfusion type. Kaplan-Meier estimates were used to estimate 30-day postoperative survival. RESULTS: Six thousand four hundred thirty-seven patients underwent surgical repair of acute TAAD, of whom 2642 (41%) had 1 or more preoperative malperfusion syndromes. Mesenteric malperfusion (adjusted odds ratio [AOR], 4.84; P < .001) was associated with the highest odds of in-hospital mortality, followed by coma (AOR, 1.88; P = .007), limb ischemia (AOR, 1.73; P = .008), and coronary malperfusion (AOR, 1.51; P = .02). Renal malperfusion (AOR, 1.37; P = .24) and neurologic deficit (AOR, 1.35; P = .28) were not associated with increased in-hospital mortality. In patients who survived to discharge, there was no difference in 1-year postdischarge survival in the malperfusion and no malperfusion cohorts (P = .36). CONCLUSIONS: Survival during the index admission after TAAD repair varies according to the presence and type of malperfusion syndromes, with mesenteric malperfusion being associated with the highest odds of in-hospital death. Not only the presence of malperfusion but rather specific malperfusion syndromes should be considered when assessing a patient's risk of undergoing TAAD repair.

2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. STRUCTURE: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.

Aortic Cellular Diversity and Quantitative Genome-Wide Association Study Trait Prioritization Through Single-Nuclear RNA Sequencing of the Aneurysmal Human Aorta.

BACKGROUND: Mural cells in ascending aortic aneurysms undergo phenotypic changes that promote extracellular matrix destruction and structural weakening. To explore this biology, we analyzed the transcriptional features of thoracic aortic tissue. METHODS: Single-nuclear RNA sequencing was performed on 13 samples from human donors, 6 with thoracic aortic aneurysm, and 7 without aneurysm. Individual transcriptomes were then clustered based on transcriptional profiles. Clusters were used for between-disease differential gene expression analyses, subcluster analysis, and analyzed for intersection with genetic aortic trait data. RESULTS: We sequenced 71 689 nuclei from human thoracic aortas and identified 14 clusters, aligning with 11 cell types, predominantly vascular smooth muscle cells (VSMCs) consistent with aortic histology. With unbiased methodology, we found 7 vascular smooth muscle cell and 6 fibroblast subclusters. Differentially expressed genes analysis revealed a vascular smooth muscle cell group accounting for the majority of differential gene expression. Fibroblast populations in aneurysm exhibit distinct behavior with almost complete disappearance of quiescent fibroblasts. Differentially expressed genes were used to prioritize genes at aortic diameter and distensibility genome-wide association study loci highlighting the genes JUN, LTBP4 (latent transforming growth factor beta-binding protein 1), and IL34 (interleukin 34) in fibroblasts, ENTPD1, PDLIM5 (PDZ and LIM domain 5), ACTN4 (alpha-actinin-4), and GLRX in vascular smooth muscle cells, as well as LRP1 in macrophage populations. CONCLUSIONS: Using nuclear RNA sequencing, we describe the cellular diversity of healthy and aneurysmal human ascending aorta. Sporadic aortic aneurysm is characterized by differential gene expression within known cellular classes rather than by the appearance of novel cellular forms. Single-nuclear RNA sequencing of aortic tissue can be used to prioritize genes at aortic trait loci.

Early Mortality in Type A Acute Aortic Dissection: Insights From the International Registry of Acute Aortic Dissection.

Importance: Early data revealed a mortality rate of 1% to 2% per hour for type A acute aortic dissection (TAAAD) during the initial 48 hours. Despite advances in diagnostic testing and treatment, this mortality rate continues to be cited because of a lack of contemporary data characterizing early mortality and the effect of timely surgery. Objective: To examine early mortality rates for patients with TAAAD in the contemporary era. Design, Setting, and Participants: This cohort study examined data for patients with TAAAD in the International Registry of Acute Aortic Dissection between 1996 and 2018. Patients were grouped according to the mode of their intended treatment, surgical or medical. Exposure: Surgical treatment. Main Outcomes and Measures: Mortality was assessed in the initial 48 hours after hospital arrival using Kaplan-Meier curves. In-hospital complications were also evaluated. Results: A total of 5611 patients with TAAAD were identified based on intended treatment: 5131 (91.4%) in the surgical group (3442 [67.1%] male; mean [SD] age, 60.4 [14.1] years) and 480 (8.6%) in the medical group (480 [52.5%] male; mean [SD] age, 70.9 [14.7] years). Reasons for medical management included advanced age (n = 141), comorbidities (n = 281), and patient preference (n = 81). Over the first 48 hours, the mortality for all patients in the study was 5.8%. Among patients who were medically managed, mortality was 0.5% per hour (23.7% at 48 hours). For those whose intended treatment was surgical, 48-hour mortality was 4.4%. In the surgical group, 51 patients (1%) died before the operation. Conclusions and Relevance: In this study, the overall mortality rate for TAAAD was 5.8% at 48 hours. For patients in the medical group, TAAAD had a mortality rate of 0.5% per hour (23.7% at 48 hours). However, among those in the surgical group, 48-hour mortality decreased to 4.4%.

Location of Aortic Enlargement and Risk of Type A Dissection at Smaller Diameters.

BACKGROUND: Previous work has demonstrated that more than one-half of acute type A aortic dissections (ATADs) occur at a maximal aortic diameter (MAD) of <5.5 cm. However, no analysis has investigated whether ATAD risk at smaller MADs is more common with modest dilation of the aortic root (AR) or supracoronary ascending aorta (AA) in patients without genetically triggered aortopathy. OBJECTIVES: This study sought to determine if the segment of modest aortic dilation affects risk of ATAD. METHODS: Using the International Registry of Acute Aortic Dissection (IRAD) database from May 1996 to October 2016, we identified 667 ATAD patients with MAD <5.5 cm. Patients were stratified by location of the largest proximal aortic segment (AR or AA). Patients with known genetically triggered aortopathy were excluded. MADs at time of dissection were compared between AR and AA groups. Secondary outcomes included operation, postoperative outcomes, and long-term survival. RESULTS: Of patients with ATAD at an MAD <5.5 cm, 79.5% (n = 530) were in the AA group and 20.5% (n = 137) in the AR group. Modestly dilated ARs (median MAD 4.6 cm [IQR: 4.1-5.0 cm]) dissected at a significantly smaller diameter than modestly dilated AAs (median MAD 4.8 cm [IQR: 4.4-5.1 cm]) (P < 0.01). AR patients were significantly younger than AA patients (58.5 ± 13.0 years vs 63.2 ± 13.3 years; P < 0.01) and more commonly male (78% vs 65%; P < 0.01). Postoperative and long-term outcomes did not differ between groups. CONCLUSIONS: ATAD appears to occur at smaller diameters in patients with modest dilation in the AR vs the AA (4.6 vs 4.8 cm). These findings may have implications for future consensus guidelines regarding the management of patients with aortic disease.

Engaging frontline employees using innovation contests: Lessons from Massachusetts General Hospital.

In this article, we describe how innovation contests-a vehicle to crowdsource ideas and problem-solving efforts-propelled frontline employees to exert discretionary efforts in organizational problem-solving at Massachusetts General Hospital. As designers and administrators of four innovation contests in three disease centers, we share firsthand knowledge of how the contests enabled clinicians and administrative staff, whose primary job is delivering high-quality patient care, to become involved in ideation, selection, and implementation of their own ideas. We describe the processes that we designed and implemented, ideas that these processes generated, and findings from interviewing employees about their experiences afterwards. Our findings suggest that the benefits of implementing innovation contests were multifaceted. To employees, the contests provided a platform to voice suggestions and participate in any aspect of the innovation process that they found interesting. To managers, the contests revealed real, empirical issues affecting operation and patient care based on frontline employees' knowledge. To the organization as a whole, the contests promoted collaborative problem-solving among likeminded, innovative employees.

Vascular smooth muscle cell phenotype switching in carotid atherosclerosis.

Carotid plaque instability contributes to large vessel ischemic stroke. Although vascular smooth muscle cells (VSMCs) affect atherosclerotic growth and instability, no treatments aimed at improving VSMC function are available. Large genetic studies investigating atherosclerosis and carotid disease in relation to the risk of stroke have implicated polymorphisms at the HDAC9 locus. The HDAC9 protein has been shown to affect the VSMC phenotype; however, how this might affect carotid disease is unknown. We conducted a pilot investigation using single nuclei RNA sequencing of human carotid tissue to identify cells expressing HDAC9 and specifically investigate the role of the HDAC9 in carotid atherosclerosis. We found that carotid VSMCs express HDAC9 and genes typically associated with immune characteristics. Using cellular assays, we have demonstrated that recruitment of macrophages can be modulated by HDAC9 expression. HDAC9 expression might affect carotid plaque stability and progression through its effects on the VSMC phenotype and recruitment of immune cells.

Type A Acute Aortic Dissection Presenting With Cerebrovascular Accident at Advanced Age.

Our aim was to analyze outcomes of patients aged 70 years or above presenting with type A acute aortic dissection (TAAAD) and cerebrovascular accident (CVA). A retrospective analysis of the International Registry of Acute Aortic Dissection (IRAD) was conducted. Patients aged 70 years or above (n = 1449) were stratified according to presence or absence of CVA before surgery (CVA: n = 110, 7.6%). In-hospital outcomes and mortality up to 5 years were analyzed. Additionally, in-hospital outcomes of patients who received medical management were described. No patient presenting with CVA over the age of 87 years underwent surgery. The rates of in-hospital mortality and post-operative CVA were significantly higher in patients presenting with CVA (in-hospital mortality: 32.7% vs 21.7%, P = 0.008; post-operative CVA: 23.4% vs 8.3%, P < 0.001). Presence of CVA was independently associated with significantly increased in-hospital mortality (odds ratio 2.99, 95% confidence interval 1.35 - 6.60, P = 0.007). In survivors of the hospital stay, presenting CVA had no independent influence on mortality up to 5 years (hazard ratio 1.52, 95% confidence interval 0.99 - 2.31, P = 0.54). In medically managed patients, exceedingly high rates of in-hospital mortality (71.4%) and CVA (90.9%) were noted. Patients presenting with TAAAD and CVA at ≥ 70 years of age are at significantly increased risk of in-hospital mortality, although long-term mortality is not affected in hospital survivors. Medical management is associated with poor outcomes. We believe that surgical management should be offered after critical assessment of comorbidities.