Ketamine as an Adjunct Therapy in Acute Severe Asthma: An In-Depth Review of Efficacy and Clinical Implications.

Acute severe asthma, formerly named status asthmaticus, is defined as a life-threatening asthma exacerbation that is refractory to the current standards of treatment such as the use of beta-agonists and epinephrine. This complication of asthma affects up to 15% of individuals with asthma and despite critical care treatment and hospitalization, there remains a staggeringly high 10-18% mortality rate in an intensive care unit setting. The addition of ketamine to the arsenal of acute severe asthma treatment due to its rapid onset, variable routes of administration, and overall improved clinical efficacy in treatment-refractory cases has been well investigated and documented. Ketamine's anti-inflammatory properties, bronchodilatory effects, and well-documented history contribute to its ability to provide a significant clinical asthma score (CAS) reduction and improvement on pulmonary readings, such as peak expiratory flow (PEF), while providing a well-researched adverse effect profile. This article serves to analyze and review the benefits and risks of incorporating ketamine into the standard treatment regimen for patients suffering from acute severe asthma and discusses the implications of such implementation.

Geographic access to cardiac rehabilitation and cardiovascular disease outcomes: A study of rural United States counties.

Prior studies have examined rural-urban disparities in access to cardiac rehabilitation (CR). However, few have examined the relationship between disparate access to CR and cardiovascular disease outcomes in rural areas. In this analysis of 1975 nonmetro United States counties, we investigated the relationship between number of hospitals with CR and Medicare-population hospitalization rates (per 1000 adults ≥65 years) and county-population mortality rates (per 100,000 adults ≥18 years) due to coronary heart disease (CHD), heart failure (HF), or stroke, using multivariable linear-regression-modeling adjusting for socio-demographic and comorbid conditions. Median CHD hospitalization (13.0 vs. 12.2), HF hospitalization (16.1 vs. 13.3), HF death (114.2 vs. 110.9), stroke hospitalization (12.0 vs. 10.9), and stroke death (39.6 vs. 37.1) rates were higher in nonmetro counties without versus with a CR facility (p-values< 0.001). There were inverse correlations between number of hospitals with CR and CHD (r= -0.161), HF (r= -0.261) and stroke (r= -0.237) hospitalization rates, and stroke mortality (r= -0.144) rates (p-values< 0.001). After adjustment, as the number of hospitals with CR increased, there were decreases in hospitalization rates of 1.78 for CHD, 7.20 for HF, and 2.43 for stroke, per 1000 in the population (p-values < 0.001) and decreases in stroke deaths of 9.17 per 100,000 in the population (p= 0.02). Access to hospitals with CR in US nonmetro counties is inversely related to CHD, HF, and stroke hospitalization, and stroke mortality. Our findings call for reducing barriers to CR in nonmetro communities and further exploring the relationship between CR and stroke outcomes.

Single-cell atlas of the human brain vasculature across development, adulthood and disease.

A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood1. Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We identify extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across five vascular-dependent central nervous system (CNS) pathologies, including brain tumours and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict substantial endothelial-to-perivascular cell ligand-receptor cross-talk, including immune-related and angiogenic pathways, thereby revealing a central role for the endothelium within brain neurovascular unit signalling networks. Our single-cell brain atlas provides insights into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies.

Incidence, risk factors, and long-term outcomes associated with permanent pacemaker implantation after aortic root replacement.

OBJECTIVE: Permanent pacemaker implantation (PPI) after aortic valve replacement is associated with long-term mortality. However, data regarding PPI after aortic root replacement (ARR) is lacking. Herein we describe the incidence, risk factors, and long-term outcomes of PPI after ARR. METHODS: Consecutive patients undergoing ARR from 2005 to 2020 were selected after excluding those with endocarditis, type A dissection, or preoperative PPI. Patients requiring PPI after ARR were identified, along with the indication and timing. Independent factors associated with PPI after ARR were identified and long-term survival was assessed. RESULTS: The incidence of PPI was 3.8% (n = 85) among 2240 patients undergoing ARR. PPI was performed a median of 7 days (interquartile range, 5-12 days) after ARR most commonly for complete heart block (73%). Bicuspid aortic valve (odds ratio [OR], 1.89; P = .02), female sex (OR, 1.74; P = .04), preoperative heart block (OR, 2.70; P = .02), and prior aortic valve replacement (OR, 2.18; P = .01) were independently associated with PPI while preoperative aortic insufficiency (OR, 0.52; P = .01) and valve-sparing root replacement procedure compared with bio-Bentall (OR, 0.40; P = .01) were protective. Patients requiring PPI after ARR were not at increased risk of operative or long-term mortality compared with patients not requiring PPI (P = .26); however, those undergoing PPI experienced significantly longer hospital length of stay (13 vs 7 days; P < .001). CONCLUSIONS: The incidence of PPI after ARR remains low, particularly after VSRR. Preoperative conduction disturbance, prior AVR, and bicuspid aortic valve are all associated with increased risk of PPI. Although PPI is associated with longer length of stay, it is not associated with early or late mortality.

Chest CT Imaging Provides More Information Than Chest Radiography Alone in Determining Extent of Physiologic Impairment in Pulmonary Sarcoidosis.

BACKGROUND: Sarcoidosis staging primarily has relied on the Scadding chest radiographic system, although chest CT imaging is finding increased clinical use. RESEARCH QUESTION: Whether standardized chest CT scan assessment provides additional understanding of lung function beyond Scadding stage and demographics is unknown and the focus of this study. STUDY DESIGN AND METHODS: We used the National Heart, Lung, and Blood Institute study Genomics Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis cases of sarcoidosis (n = 351) with Scadding stage and chest CT scans obtained in a standardized manner. One chest radiologist scored all CT scans with a visual scoring system, with a subset read by another chest radiologist. We compared demographic features, Scadding stage, and CT scan findings and the correlation between these measures. Associations between spirometry results and Dlco, CT scan findings, and Scadding stage were determined using regression analysis (n = 318). Agreement between readers was evaluated using Cohen's κ value. RESULTS: CT scan features were inconsistent with Scadding stage in approximately 40% of cases. Most CT scan features assessed on visual scoring were associated negatively with lung function. Associations persisted for FEV1 and Dlco when adjusting for Scadding stage, although some CT scan feature associations with FVC became insignificant. Scadding stage was associated primarily with FEV1, and inclusion of CT scan features reduced significance in association between Scadding stage and lung function. Multivariable regression modeling to identify radiologic measures explaining lung function included Scadding stage for FEV1 and FEV1 to FVC ratio (P < .05) and marginally for Dlco (P < .15). Combinations of CT scan measures accounted for Scadding stage for FVC. Correlations among Scadding stage and CT scan features were noted. Agreement between readers was poor to moderate for presence or absence of CT scan features and poor for degree and location of abnormality. INTERPRETATION: CT scan features explained additional variability in lung function beyond Scadding stage, with some CT scan features obviating the associations between lung function and Scadding stage. Whether CT scan features, phenotypes, or endotypes could be useful for managing patients with sarcoidosis needs more study.

Pulmonary sarcoidosis: differences in lung function change over time.

INTRODUCTION: Given the heterogeneity of sarcoidosis, predicting disease course of patients remains a challenge. Our aim was to determine whether the 3-year change in pulmonary function differed between pulmonary function phenotypes and whether there were differential longitudinal changes by race and sex. METHODS: We identified individuals seen between 2005 and 2015 with a confirmed diagnosis of sarcoidosis who had at least two pulmonary function test measurements within 3 years of entry into the cohort. For each individual, spirometry, diffusion capacity, Charlson Comorbidity Index, sarcoidosis organ involvement, diagnosis duration, tobacco use, race, sex, age and medications were recorded. We compared changes in pulmonary function by type of pulmonary function phenotype and for demographic groups. RESULTS: Of 291 individuals, 59% (173) were female and 54% (156) were black. Individuals with restrictive pulmonary function phenotype had significantly greater 3-year rate of decline of FVC% (forced vital capacity) predicted and FEV1% (forced expiratory volume in 1 s) predicted course when compared with normal phenotype. We identified a subset of individuals in the cohort, highest decliners, who had a median 3-year FVC decline of 156 mL. Black individuals had worse pulmonary function at entry into the cohort measured by FVC% predicted, FEV1% predicted and diffusing capacity for carbon monoxide % predicted compared with white individuals. Black individuals' pulmonary function remained stable or declined over time, whereas white individuals' pulmonary function improved over time. There were no sex differences in rate of change in any pulmonary function parameters. SUMMARY: We found significant differences in 3-year change in pulmonary function among pulmonary function phenotypes and races, but no difference between sexes.

Open, endovascular or hybrid repair of aortic arch disease: narrative review of diverse strategies with diverse options.

OBJECTIVES: The management of aortic arch disease is complex. Open surgical management continues to evolve, and the introduction of endovascular repair is revolutionizing aortic arch surgery. Although these innovative techniques have generated the opportunity for better outcomes in select patients, they have also introduced confusion and uncertainty regarding best practices. METHODS: In New York, we developed a collaborative group, the New York Aortic Consortium, as a means of cross-linking knowledge and working together to better understand and treat aortic disease. In our meeting in May 2023, regional aortic experts and invited international experts discussed the contemporary management of aortic arch disease, differences in interpretation of the available literature and the integration of endovascular technology into disease management. We summarized the current state of aortic arch surgery in this review article. RESULTS: Approaches to aortic arch repair have evolved substantially, whether it be methods to reduce cerebral ischaemia, improve haemostasis, simplify future operations or expand options for high-risk patients with endovascular approaches. However, the transverse aortic arch remains challenging to repair. Among our collaborative group of cardiac/aortic surgeons, we discovered a wide disparity in our practice patterns and our management strategies of patients with aortic arch disease. CONCLUSIONS: It is important to build unique institutional expertise in the context of complex and evolving management of aortic arch disease with open surgery, endovascular repair and hybrid approaches, tailored to the risk profiles and anatomical specifics of individual patients.

Long-term outcomes after aortic root replacement for bicuspid aortic valve-associated aneurysm.

OBJECTIVE: Patients with congenital bicuspid aortic valve often require root replacement. This study aims to describe their long-term rates of mortality and reoperation. METHODS: This is a multicenter retrospective study of 747 patients with bicuspid aortic valve who underwent aortic root replacement for aortic aneurysm between 2004 and 2020. Cumulative incidence curves for aortic valve and aortic reoperations were graphed. A Kaplan-Meier survival curve for the patient cohort was created alongside an age- and sex-matched curve for the US population. Multivariable Cox regression was used to determine characteristics associated with long-term mortality. RESULTS: The median age of our cohort was 54 [43-64] years old, and 101 (13.5%) patients were female. In patients with bicuspid aortic valve dysfunction, 274 (36.7%) had aortic insufficiency, 187 (25.0%) had aortic stenosis, and 142 (19.0%) had both. In-hospital mortality occurred in 10 (1.3%) patients. There were 56 aortic valve reoperations and 19 aortic reoperations, with a combined cumulative incidence of 35% (95% confidence interval [CI], 23%-46%) at 15 years. In addition, there was comparable survival between the patient cohort and the age- and sex-matched US population. Age (hazard ratio [HR], 1.04; 95% CI, 1.01-1.06), concomitant CABG (HR, 2.28; 95% CI, 1.29-4.04), and bypass time (HR, 1.01; 95% CI, 1.00-1.01) were associated with increased mortality. CONCLUSIONS: Patients who undergo aortic root replacement with bicuspid aortic valve have an increased rate of aortic reoperation (35%; 95% CI, 23%-46%) while their survival appears to be comparable to the general US population (79%; 95% CI, 73%-87%) at 15 years.

Design and Synthesis of P(AAm-co-NaAMPS)-Alginate-Xanthan Hydrogels and the Study of Their Mechanical and Rheological Properties in Artificial Vascular Graft Applications.

Cardiovascular diseases (CVDs) are the number one cause of mortality among non-communicable diseases worldwide. Expanded polytetrafluoroethylene (ePTFE) is a widely used material for making artificial vascular grafts to treat CVDs; however, its application in small-diameter vascular grafts is limited by the issues of thrombosis formation and intimal hyperplasia. This paper presents a novel approach that integrates a hydrogel layer on the lumen of ePTFE vascular grafts through mechanical interlocking to efficiently facilitate endothelialization and alleviate thrombosis and restenosis problems. This study investigated how various gel synthesis variables, including N,N'-Methylenebisacrylamide (MBAA), sodium alginate, and calcium sulfate (CaSO4), influence the mechanical and rheological properties of P(AAm-co-NaAMPS)-alginate-xanthan hydrogels intended for vascular graft applications. The findings obtained can provide valuable guidance for crafting hydrogels suitable for artificial vascular graft fabrication. The increased sodium alginate content leads to increased equilibrium swelling ratios, greater viscosity in hydrogel precursor solutions, and reduced transparency. Adding more CaSO4 decreases the swelling ratio of a hydrogel system, which offsets the increased swelling ratio caused by alginate. Increased MBAA in the hydrogel system enhances both the shear modulus and Young's modulus while reducing the transparency of the hydrogel system and the pore size of freeze-dried samples. Overall, Hydrogel (6A12M) with 2.58 mg/mL CaSO4 was the optimal candidate for ePTFE-hydrogel vascular graft applications due to its smallest pore size, highest shear storage modulus and Young's modulus, smallest swelling ratio, and a desirable precursor solution viscosity that facilitates fabrication.

A Review of Sodium-Glucose Cotransporter 2 Inhibitor's Clinical Efficacy in Heart Failure With Preserved Ejection Fraction.

Heart failure (HF) poses a significant healthcare burden, with distinct subtypes based on ventricular function. HF with preserved ejection fraction (HFpEF) presents unique epidemiological and mechanistic features compared to HF with reduced ejection fraction (HFrEF). The pathophysiology of HFpEF is complex and involves multiple factors. Current pharmacological therapies for HFpEF remain suboptimal, with inconsistent mortality outcomes observed despite improvements in symptoms and quality of life. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as promising agents in HF management and hospitalizations, particularly in HFpEF patients. The cardioprotective mechanisms of SGLT2 inhibitors are multifactorial. In this article, we performed a comprehensive review of SGLT2 inhibitor use in HFpEF and discussed the implications in the management of HF.

Acute type A aortic syndromes: outcomes are independent of aortic root/valve management.

Purpose: Clinical outcomes following various surgical intervention strategies for aortic root and valve pathology during repair of acute type A aortic syndromes were studied and compared. Methods: From 2004 to 2019, 634 patients underwent acute type A aortic repair. Patients were divided into 4 groups: Valve Resuspension (n = 456), Isolated Valve Replacement (AVR) (n = 24), Valve and Root Replacement (ROOT) (n = 97), and Valve Sparing Root Replacement (VSRR) (n = 57). The primary endpoint was midterm survival and multivariable risk factor analysis was performed. Results: The mean age was 55.4 ± 13 years, 424 (67%) were male, and overall early mortality was 12%. Early mortality was 13%, 8%, 11%, and 7% for the Valve Resuspension, AVR, ROOT, and VSRR groups respectively, p = 0.43. Five-year survival was 74%, 86%, 73%, and 84% for the Valve Resuspension, AVR, ROOT, and VSRR groups respectively, p = 0.46. There was no difference in late stroke, renal failure, heart block, and late bleeding (p > 0.05 for all). At late follow-up, AVR and ROOT patients had a higher mean gradient versus Valve Resuspension and VSRR patients, p < 0.0001. For the total cohort, risk factors for late mortality included preoperative peripheral vascular disease (hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.4, p = 0.009) and preoperative dialysis (HR 2.8, 95% CI 1.3-6.1, p = 0.01). Conclusion: Mid-term survival following repair of acute type A aortic dissection is not independently associated with a specific type of aortic valve intervention. Native valve preservation leads to acceptable mid-term valve hemodynamics and should be the preferred therapy in this emergent clinical setting. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01602-8.

Evaluating left atrial strain and left ventricular diastolic strain rate as markers for diastolic dysfunction in patients with mitral annular calcification.

BACKGROUND: Mitral annular calcification (MAC) poses many challenges to the evaluation of diastolic function using standard echocardiography. Left atrial (LA) strain and left ventricular early diastolic strain rate (DSr) measured by speckle-tracking echocardiography (STE) are emerging techniques in the noninvasive evaluation of diastolic function. We aim to evaluate the utility of LA strain and early DSr in predicting elevated left ventricular filling pressures (LVFP) in patients with MAC and compare their effectiveness to ratio of mitral inflow velocity in early and late diastole (E/A). METHODS: We included adult patients with MAC who presented between January 1 and December 31, 2014 and received a transthoracic echocardiogram (TTE) and cardiac catheterization with measurement of LVFP within a 24-h period. We used Spearman's rank correlation coefficient to assess associations of LA reservoir strain and average early DSr with LVFP. Receiver operating characteristic (ROC) curves were computed to assess the effectiveness of LA strain and DSr in discriminating elevated LVFP as a dichotomized variable and to compare their effectiveness with E/A ratio categorized according to grade of diastolic dysfunction. RESULTS: Fifty-five patients were included. LA reservoir strain demonstrated poor correlation with LVFP (Spearman's rho = 0.03, p = 0.81) and poor discriminatory ability for detecting elevated LVFP (AUC = 0.54, 95% CI 0.38-0.69). Categorical E/A ratio alone also demonstrated poor discriminatory ability (AUC = 0.53, 95% CI 0.39-0.67), and addition of LA reservoir strain did not significantly improve effectiveness (AUC = 0.58, 95% CI 0.42-0.74, p = 0.56). Average early DSr also demonstrated poor correlation with LVFP (Spearman's rho = -0.19, p = 0.16) and poor discriminatory ability for detecting elevated LVFP (AUC = 0.59, 95% CI 0.44-0.75). Addition of average early DSr to categorical E/A ratio failed to improve effectiveness (AUC = 0.62, 95% CI 0.46-0.77 vs. AUC = 0.54, 95% CI 0.39-0.69, p = 0.38). CONCLUSIONS: In our sample, LA reservoir strain and DSr do not accurately predict diastolic filling pressure. Further research is required before LA strain and early DSr can be routinely used in clinical practice to assess filling pressure in patients with MAC.

Left atrial strain, embolic stroke of undetermined source, and atrial fibrillation detection.

BACKGROUND: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. METHODS: The study population included patients with ESUS and noncardioembolic (NCE) stroke presenting to the Rhode Island Hospital Stroke Center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the three phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow-up detection of AF in ESUS patients. RESULTS: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266-2.986, p = .002), contractile (aOR 1.568, 95% CI 1.035-2.374, p = .034), and conduit strain (aOR 2.288, 95% CI 1.448-3.613, p = .001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029-6.236, p = .043), contractile strain (OR 2.828, 95% CI 1.158-6.903, p = .022), and conduit strain (OR 2.614, 95% CI 1.003-6.815, p = .049) were significantly associated with subsequent detection of AF. CONCLUSION: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies.

Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest Trial (GOT ICE): A Randomized Clinical Trial Comparing Outcomes After Aortic Arch Surgery.

BACKGROUND: Deep hypothermia has been the standard for hypothermic circulatory arrest (HCA) during aortic arch surgery. However, centers worldwide have shifted toward lesser hypothermia with antegrade cerebral perfusion. This has been supported by retrospective data, but there has yet to be a multicenter, prospective randomized study comparing deep versus moderate hypothermia during HCA. METHODS: This was a randomized single-blind trial (GOT ICE [Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest]) of patients undergoing arch surgery with HCA plus antegrade cerebral perfusion at 4 US referral aortic centers (August 2016-December 2021). Patients were randomized to 1 of 3 hypothermia groups: DP, deep (≤20.0 °C); LM, low-moderate (20.1-24.0 °C); and HM, high-moderate (24.1-28.0 °C). The primary outcome was composite global cognitive change score between baseline and 4 weeks postoperatively. Analysis followed the intention-to-treat principle to evaluate if: (1) LM noninferior to DP on global cognitive change score; (2) DP superior to HM. The secondary outcomes were domain-specific cognitive change scores, neuroimaging findings, quality of life, and adverse events. RESULTS: A total of 308 patients consented; 282 met inclusion and were randomized. A total of 273 completed surgery, and 251 completed the 4-week follow-up (DP, 85 [34%]; LM, 80 [34%]; HM, 86 [34%]). Mean global cognitive change score from baseline to 4 weeks in the LM group was noninferior to the DP group; likewise, no significant difference was observed between DP and HM. Noninferiority of LM versus DP, and lack of difference between DP and HM, remained for domain-specific cognitive change scores, except structured verbal memory, with noninferiority of LM versus DP not established and structured verbal memory better preserved in DP versus HM (P = 0.036). There were no significant differences in structural or functional magnetic resonance imaging brain imaging between groups postoperatively. Regardless of temperature, patients who underwent HCA demonstrated significant reductions in cerebral gray matter volume, cortical thickness, and regional brain functional connectivity. Thirty-day in-hospital mortality, major morbidity, and quality of life were not different between groups. CONCLUSIONS: This randomized multicenter study evaluating arch surgery HCA temperature strategies found low-moderate hypothermia noninferior to traditional deep hypothermia on global cognitive change 4 weeks after surgery, although in secondary analysis, structured verbal memory was better preserved in the deep group. The verbal memory differences in the low- and high-moderate groups and structural and functional connectivity reductions from baseline merit further investigation and suggest opportunities to further optimize brain perfusion during HCA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02834065.

Reintervention after valve-sparing aortic root replacement: A comprehensive analysis of 781 David V procedures.

OBJECTIVE: Studies of reintervention after valve-sparing aortic root replacement (VSRR) are limited by sample size and failure to evaluate all types of reinterventions, including distal aorta and transcatheter interventions. In this report, reintervention after VSRR using a large patient cohort was comprehensively analyzed. METHODS: In a series involving 2 academic aortic centers, 781 consecutive patients from 2005 to 2020 undergoing David V VSRR for aortic aneurysm (91%) or dissection (9%) were included. Median age was 50 years, and 23% had a bicuspid aortic valve (AV). Median follow-up was 7.0 years. Open or transcatheter reintervention on the AV, proximal, or distal thoracic aorta was identified. Cumulative incidence was calculated, and subdistribution hazard models identified factors associated with reintervention. Time-dependent incidence of reintervention was plotted using risk-hazard functions. RESULTS: Sixty-eight reinterventions (57 open, 11 transcatheter) were performed. Reinterventions were divided by indication into degenerative AV (n = 26, including 1 transcatheter aortic valve replacement), endocarditis (n = 11), proximal aorta (n = 8), and distal aorta (n = 23, including 10 thoracic endovascular aortic repairs). Risk of reintervention for endocarditis peaked 1 to 3 years after VSRR, whereas other indications had stable, low rates of occurrence throughout the follow-up period. The cumulative incidence of reintervention was 12.5% whereas the cumulative incidence of AV reintervention was 7.0% at 10 years and was associated with residual postoperative aortic insufficiency. In-hospital mortality after reintervention was 3%. CONCLUSIONS: Reintervention rates after VSRR are relatively low in long-term follow-up and can be performed with acceptable operative risk. The majority of reinterventions are performed for indications other than AV degeneration, with the timing of reintervention varying by the specific clinical indication.