Natural History of Mitral Regurgitation After Transcatheter Aortic Valve Implantation.

BACKGROUND: This study sought to determine the impact of mitral regurgitation (MR) on outcomes after transcatheter aortic valve implantation (TAVI). METHODS: This was an observational study of TAVI for aortic stenosis (AS) from November 2012 to December 2021; 25% of patients were excluded because post-TAVI echocardiograms were unavailable. Excluded patients had a higher Society of Thoracic Surgeons predicted risk of mortality score than included patients (5.6% vs 4.9%). Patients were dichotomized according to the severity of pre-TAVI MR: < moderate vs ≥ moderate. RESULTS: A total of 2250 patients underwent TAVI, of whom 329 (14.6%) had MR ≥ moderate before TAVI. Baseline MR ≥ moderate was associated with reduced survival (46.2% for MR ≥ moderate vs 58.7% for MR < moderate; P < .001) and a higher incidence of heart failure readmission at 5 years after TAVI; 11% of patients had progression or persistence of MR ≥ moderate at 1 year after TAVI, which was also associated with reduced survival. On multivariable logistic regression, increasing age, women, lower ejection fraction, prior acute coronary syndrome, concomitant aortic insufficiency ≥ moderate, low-flow low-gradient AS, pulmonary hypertension, baseline tricuspid regurgitation ≥ moderate, and lower mean pre-TAVI aortic transvalvular pressure gradient were associated with progression or persistence of MR ≥ moderate at 1 year after TAVI, whereas procedural variables and postprocedural complications were not. CONCLUSIONS: Significant MR before and after TAVI was associated with reduced survival. Whereas various clinical variables were associated with significant MR after TAVI, periprocedural variables were not. Evolution of MR must be carefully surveilled after TAVI, and more data are needed to establish guidelines for managing mixed AS and MR.

Supra-Annular Self-Expanding Versus Balloon-Expandable Valves for Valve-in-Valve Transcatheter Aortic Valve Replacement.

Self-expanding (SE) and balloon-expandable (BE) transcatheter heart valves (THVs) have not been extensively studied in valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR). We compared outcomes of supra-annular SE and BE THVs used for ViV-TAVR through a retrospective analysis of institutional data (2013 to 2023) including all patients who underwent ViV-TAVR (TAVR in previous surgical aortic valve replacement). Unmatched and propensity-matched (1:1) comparisons of clinical and echocardiographic outcomes were undertaken in SE and BE THVs along with Kaplan-Meier survival analysis. A total of 315 patients who underwent ViV-TAVR were included, of whom 73% received an SE THV. Median age was 77 years, and women comprised 42.5% of the population. Propensity-score matching (1:1) yielded 81 matched pairs. Implanted aortic valve size was comparable in the groups (23 mm [23 to 26] vs 23 mm [23 to 26], p = 0.457). At 30 days after ViV-TAVR, the SE group had a lower mean aortic valve gradient (14 mm Hg [11 to 18] vs 17.5 mm Hg [13 to 25], p = 0.007). A greater number of patients with BE THV had severe prosthesis-patient mismatch (16% vs 6.2%, p = 0.04). At 1-year follow-up, the SE THV group had a lower aortic valve gradient (14.0 mm Hg [9.6 to 19] vs 17 mm Hg [13 to 25], p = 0.04) than that of the BE THV group; 30-day mortality was 2.7%, whereas 1-year mortality was 7.5% and comparable in the groups. Survival and stroke incidence were similar in the groups up to 5 years. In conclusion, SE and BE THVs had comparable survival after ViV-TAVR. The higher residual aortic valve gradients in BE THVs are likely due to valve design and warrant long-term evaluation for potential structural valve degeneration.

Risk factors and operative risk of large vessel occlusion and stroke during cardiac surgery.

OBJECTIVE: Perioperative Large Vessel Occlusions (LVOs) occurring during and following surgery are of immense clinical importance. As such, we aim to present risk factors and test if the Society of Thoracic Surgery (STS) mortality and stroke risk scores can be used to assess operative risk. METHODS: Using data containing 7 index cardiac operations at a single tertiary referral center from 2010 to 2022, logistic and multivariate regression analysis was performed to identify factors that correlate to higher operative LVO and stroke rate. Odds ratios and confidence intervals were also obtained to test if the STS-Predicted Risk of Mortality (PROM) and -Predicted Risk of Stroke (PROS) scores were positively correlated to operative LVO and stroke rate. RESULTS: Multivariate modeling showed primary risk factors for an operative LVO were diabetes (OR: 1.727 [95 % CI: 1.060-2.815]), intracranial or extracranial carotid stenosis (OR: 3.661 [95 % CI: 2.126-6.305]), and heart failure as defined by NYHA class (Class 4, OR: 3.951 [95 % CI: 2.092-7.461]; compared to Class 1). As the STS-PROM increased, the relative rate of LVO occurrence increased (very high risk, OR: 6.576 [95 % CI: 2.92-14.812], high risk, OR: 2.667 [1.125-6.322], medium risk, OR: 2.858 [1.594-5.125]; all compared to low risk). STS-PROS quartiles showed a similar relation with LVO risk (quartile 4, OR: 7.768 [95 % CI: 2.740-22.027], quartile 3, OR: 5.249 [1.800-15.306], quartile 2, OR:2.980 [0.960-9.248]; all compared to quartile 1). CONCLUSIONS: Patients with diabetes, carotid disease and heart failure are at high risk for operative LVO. Both STS-PROM and -PROS can be useful metrics for preoperative measuring of LVO risks.

A novel hybrid prosthesis for open repair of acute DeBakey type I dissection with malperfusion: Early results from the PERSEVERE trial.

BACKGROUND: Outcomes after hemiarch repair for acute DeBakey type I aortic dissection (ADTI) remain unfavorable, with high rates of major adverse events and negative aortic remodeling. The PERSEVERE study evaluates the safety and effectiveness of the AMDS Hybrid prosthesis, a novel bare metal stent, in patients presenting with preoperative malperfusion. METHODS: PERSEVERE is a prospective single-arm investigational study conducted at 26 sites in the United States. Ninety-three patients underwent ADTI aortic dissection repair with AMDS implantation. The 30-day primary endpoints are a composite rate of 4 major adverse events and the rate of distal anastomotic new entry tears. The secondary endpoints include aortic remodeling. RESULTS: Clinical malperfusion was documented in 76 patients (82%); only radiographic malperfusion, in 17 (18%). The median follow-up in the 93 patients was 5.6 months. Within 30 days, 9 patients died (9.7%), 10 patients (10.8%) experienced new disabling stroke, and 18 patients (19.4%) had new-onset renal failure requiring ≥1 dialysis treatment. There were no cases of myocardial infarction. The composite rate of major adverse events (27%) was lower than that reported in the reference cohort (58%). There were no distal anastomotic new entry tears. Technical success was achieved in 99% of patients. Early remodeling indicated total aortic diameter stability, true lumen expansion, and false lumen reduction in the treated aortic segment. CONCLUSIONS: Early results show significant reductions in major adverse events and distal anastomotic new entry tears, successfully meeting both primary endpoints. The technical success rate was high. AMDS can be used safely in patients with ADTI dissection with malperfusion.

Six-Year Outcomes of Total Arch Replacement vs Debranching With TEVAR for Aortic Arch Pathologies: Meta-Analysis of Kaplan-Meier-Derived Data From Propensity Score-Matched Studies.

BACKGROUND: Total arch replacement (TAR) and debranching plus thoracic endovascular aortic repair (TEVAR) serve as significant therapeutic options for aortic arch pathologies. It remains unclear whether one of these approaches should be considered preferable. Our study aimed to compare the long-term outcomes of these 2 approaches. METHODS: We carried out a pooled meta-analysis of time-to-event data extracted from studies published by December 2023. Eligibility criteria included populations with any aortic arch pathology who underwent debranching plus TEVAR or TAR, propensity score-matched (PSM) studies (prospective/retrospective; single-center/multicentric), and the outcomes included follow-up for overall survival/mortality and/or reinterventions. RESULTS: Eleven PSM studies met our eligibility criteria, including a total of 1142 patients (571 matched pairs). We did not observe any statistically significant difference in the risk of all-cause death between the groups (hazard ratio [HR]=1.20, 95% confidence interval [CI]=0.91-1.56, p=0.202), but patients who underwent TAR had a significantly lower risk of late aortic reinterventions compared with patients who underwent debranching plus TEVAR (HR=0.38, 95% CI=0.23-0.64, p<0.001). Our meta-regression analyses for all-cause mortality identified statistically significant coefficients for age (coefficient=-0.047; p=0.012) and type A aortic dissections (coefficient=0.012; p=0.010). CONCLUSIONS: Debranching plus TEVAR and TAR demonstrate no statistically significant differences in terms of survival in patients with aortic arch pathologies, but TAR is associated with lower risk of late aortic reinterventions over time. Although older patients may benefit more from debranching plus TEVAR rather than from TAR, patients with dissections may benefit more from TAR. CLINICAL IMPACT: Although the 2 strategies seem to be equally valuable in terms of survival, total aortic arch replacement (when compared with debranching plus TEVAR to treat patients with aortic arch pathologies) is associated with reduction of late aortic reinterventions over time in patients with and without aortic dissections. However, we should consider debranching plus TEVAR in older patients as it is associated with lower risk of death in this population. The novelty of our study lies in the fact that, instead of comparing study-level effect estimates, we analyzed the outcomes with reconstructed time-to-event data. This offered us the opportunity of performing our analyses with a mathematically appropriate model which consider events and time; however, these findings might be under the influence of treatment allocation bias.

Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer's disease-related amyloid pathology.

Discovery of meningeal lymphatic vessels (LVs) in the dura mater, also known as dural LVs (dLVs) that depend on vascular endothelial growth factor C expression, has raised interest in their possible involvement in Alzheimer's disease (AD). Here we find that in the APdE9 and 5xFAD mouse models of AD, dural amyloid-ß (Aß) is confined to blood vessels and dLV morphology or function is not altered. The induction of sustained dLV atrophy or hyperplasia in the AD mice by blocking or overexpressing vascular endothelial growth factor C, impaired or improved, respectively, macromolecular cerebrospinal fluid (CSF) drainage to cervical lymph nodes. Yet, sustained manipulation of dLVs did not significantly alter the overall brain Aß plaque load. Moreover, dLV atrophy did not alter the behavioral phenotypes of the AD mice, but it improved CSF-to-blood drainage. Our results indicate that sustained dLV manipulation does not affect Aß deposition in the brain and that compensatory mechanisms promote CSF clearance.

Predictors and Trends of New Permanent Pacemaker Implantation: A Subanalysis of the International Navitor IDE Study.

Background: The Navitor Investigational Device Exemption (IDE) study is a prospective, multicenter, global study assessing the safety and effectiveness of the Navitor valve in a population with severe, symptomatic aortic stenosis who are at high and extreme surgical risk. The impact of pre-existing conduction abnormalities and implantation technique on new permanent pacemaker implantation (PPI) for the Navitor platform is not fully understood. Therefore, the goal of this analysis was to investigate the associations between patient and procedural factors and the 30-day new PPI rate. Methods: A total of 260 patients who underwent implantation of a Navitor valve in the Navitor IDE study were reviewed. Patients with preprocedural permanent pacemakers (n = 28) were excluded. Baseline risk factors were assessed for statistical significance. Multivariable logistic regression analyses were performed to identify independent predictors of new PPI. Results: Mean age of the pacemaker-naïve population was 83.3 ± 5.2 years, 58.6% were female, average Society of Thoracic Surgeons score was 3.8% ± 1.9%, median frailty score was 1 (interquartile range 1, 2), and 17.7% were deemed at extreme surgical risk. Pre-existing first-degree atrioventricular block and right bundle branch block significantly increased the risk of new PPI postimplantation, whereas left bundle branch block did not. Membranous septum length in relation to noncoronary cusp implant depth was a significant predictor of new PPI, with higher rates of new PPI observed when noncoronary cusp implant depth exceeded membranous septum length. Analysis of implant depth alone revealed deeper implants were associated with a higher rate of new PPI, regardless of patient baseline conduction abnormality. Conclusions: The 30-day rate of new PPI in the Navitor IDE study is associated with patient pre-existing baseline conduction disturbances and implantation depth.

Intravenous Methadone versus Intrathecal Morphine as Part of an Enhanced Recovery After Cardiac Surgery Protocol on Postoperative Pain and Outcomes: A Retrospective Cohort Study.

OBJECTIVES: Evaluate the effect of intravenous (IV) methadone versus intrathecal morphine (ITM) within an Enhanced Recovery After Cardiac Surgery (ERACS) pathway on postoperative pain and outcomes (length of hospital stay and postoperative complications) after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Two tertiary academic medical institutions within the same health system. PARTICIPANTS: Eligible 289 adult patients undergoing elective cardiac surgery with an enhanced recovery pathway from January 2020 through July 2021. INTERVENTIONS: Patients were administered ITM (0.25 mg) or IV methadone (0.1 mg/kg) if ITM was contraindicated. All patients were enrolled in an ERACS pathway using current Enhanced Recovery After Surgery society guidelines. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures included postoperative pain scores and opioid consumption measured as oral morphine equivalents. We analyzed patient demographics, procedural factors, intraoperative medications, and outcomes. Adjusted linear mixed models were fit to analyze associations between intervention and pain outcomes. ITM was associated with decrease in pain scores on postoperative day 0 after adjusting for clinical variables (average marginal effect, 0.49; 95% confidence interval, 0.002-0.977; p = 0.049). No difference in opioid consumption could be demonstrated between groups after adjusting for postoperative day and other variables of interest. CONCLUSIONS: ITM when compared with IV methadone was associated with a decrease in pain scores without any difference in opioid consumption after elective cardiac surgery. Methadone can be considered as a safe and effective alternative to ITM for ERACS protocols. Future large prospective studies are needed to validate this finding and further improve analgesia and safety.

Long-Term Outcomes of Mechanical Versus Bioprosthetic Aortic Valve Replacement in Patients Aged Under 50 Years: Meta-Analysis of Reconstructed Time-to-Event Data.

To compare the long-term outcomes of mechanical versus bioprosthetic aortic valve replacement (AVR) in patients aged <50 years, we performed a study-level meta-analysis with reconstructed time-to-event data including studies published by December of 2023. The primary outcome was overall survival. Secondary outcomes included reoperation, major bleeding, and stroke. A total of 5 studies met our inclusion criteria, with a total of 4,245 patients (2,311 mechanical and 1,934 bioprosthetic). All studies were observational and the mean age of groups across the studies ranged from 38.2 to 43.0 years. The median follow-up time was 11.4 years (interquartile range 6.9 to 15.0). Bioprosthetic AVR was associated with reduced overall survival and higher risk of all-cause death (hazard ratio [HR] 1.170 95% confidence interval [CI] 1.002 to 1.364, p = 0.046), increased risk of reoperation over time (HR 2.581, 95% CI 2.102 to 3.168, p <0.001), decreased risk of major bleeding (HR 0.500, 95% CI 0.367 to 0.682, p <0.001), and decreased risk of stroke (HR 0.751, 95% C, 0.565 to 0.998, p = 0.049) compared with mechanical AVR in patients aged <50 years. In conclusion, for patients aged <50 years, bioprosthetic AVR is associated with increased mortality and risk of reoperation compared with mechanical valves. In contrast, mechanical AVR is associated with an increased risk of major bleeding events and stroke. These aspects should be carefully considered during the selection of valve type in this age group; however, we should keep in mind that the statistically significant differences in the risk of all-cause death and stroke might not be clinically relevant (because of marginal statistical significance).

The burden of major complications on failure to rescue after surgery for acute type A aortic dissection: Analysis of more than 19,000 patients.

BACKGROUND: The relationship between the number and type of postoperative complications and mortality in the setting for surgery for acute type A aortic dissection (ATAAD) remains underexplored despite its critical role in the failure-to-rescue (FTR) metric. METHODS: This retrospective study used data from the Society of Thoracic Surgeons Adult Cardiac Surgical Database on ATAAD surgeries performed between January 2018 and December 2022. Patients were categorized based on their number of major complications. The primary outcome was FTR. We used multilevel regression and classification and regression tree models. RESULTS: We included 19,243 patients (33% females), with a median age of 61 years. Regarding complications, 47.7% of patients had 0, 20.2% had 1, 12.7% had 2, and 19.4% experienced 3 or more. The most frequently reported complications were prolonged mechanical ventilation (30.3%), unplanned reoperation (19.5%), and renal failure (17.2%). Cardiac arrest occurred in 7.1% of cases. FTR increased from 13% in patients with 1 complication to >30% in those with 4 or more complications. Cardiac arrest (adjusted odds ratio [aOR], 10.9) and renal failure (aOR, 5.3) had the highest odds for mortality, followed by limb ischemia (aOR, 2.7), stroke (aOR, 2.6), and gastrointestinal complications (aOR, 2.4). Hospitals in the top performance quartile consistently showed lower FTR rates across all levels of complication. CONCLUSIONS: The study validates a dose-response association between postoperative complications and mortality in patients undergoing surgery for ATAAD. Top-performing hospitals consistently show lower FTR rates independent of the number of complications. Future research should focus on the timing of complications and interventions to reduce the burden of complications.

Age-Based Outcomes After Surgical Aortic Valve Replacement With Bioprosthetic Versus Mechanical Valves.

Recommendations for prosthesis type in older patients who underwent surgical aortic valve replacement (SAVR) are established, albeit undervalidated. The purpose of this study is to compare outcomes after bioprosthetic versus mechanical SAVR across various age groups. This was a retrospective study using an institutional SAVR database. All patients who underwent isolated SAVR were compared across valve types and age strata (<65 years, 65 to 75 years, >75 years). Patients who underwent concomitant operations, aortic root interventions, or previous aortic valve replacement were excluded. Objective survival and aortic valve reinterventions were compared. Kaplan-Meier survival estimation and multivariate regression were performed. A total of 1,847 patients underwent SAVR from 2010 to 2023. A total of 1,452 patients (78.6%) received bioprosthetic valves, whereas 395 (21.4%) received mechanical valves. Of those who received bioprosthetic valves, 349 (24.0%) were aged <65 years, 627 (43.2%) were 65 to 75 years, and 476 (32.8%%) were older than 75 years. For patients who received mechanical valves, 308 (78.0%) were aged <65 years, 84 (21.3%) were between 65 and 75 years, and 3 (0.7%) were >75 years. The median follow-up in the total cohort was 6.2 (2.6 to 8.9) years. No statistically significant differences were observed in early-term Kaplan-Meier survival estimates between SAVR valve types in all age groups. However, the cumulative incidence estimates of aortic valve reintervention were significantly higher in patients aged under 65 years who received bioprosthetic than those who received mechanical valves, with 5-year reintervention rates of 5.8% and 3.1%, respectively (p = 0.002). On competing risk analysis for valve reintervention, bioprosthetic valves were significantly associated with an increased hazard of aortic valve reintervention (hazard ratio 3.35, 95% confidence interval 1.73 to 6.49, p <0.001). In conclusion, SAVR with bioprosthetic valves (particularly, in patients aged <65 years) was comparable in survival to mechanical valve SAVR but significantly associated with increased valve reintervention rates.

Transcatheter Aortic Valve Replacement in Patients With Small Aortic Annuli: A Propensity-Matched Analysis of Gender-Based Outcomes.

Patients with small aortic annuli (SAAs) are predominantly women. We sought to compare gender-based and propensity-matched outcomes of index transcatheter aortic valve replacement (TAVR) in patients with SAAs. In this retrospective institutional analysis (2012 to 2023), primary stratification was by gender. SAA was defined as an aortic valve annulus diameter <23 mm and the 30-day and 1-year outcomes were compared between the groups. A total of 3,911 patients underwent TAVR. Of those, 661 patients had an SAA, of whom 23.8% were men and 76.2% were women. Propensity matching (1:1) identified 152 pairs. The mean age was 81 years. History of surgical or percutaneous coronary intervention was more prevalent in men (72.4% vs 48%, p <0.001). Men had a higher incidence of postoperative pacemaker implantation (8.6% vs 3.3%, p = 0.05), whereas only women had iliofemoral dissections (4.6% vs 0%, p = 0.007). The rates of moderate (23.0% vs 25.7%) and severe (2.6% vs 0.7%) prosthesis-patient mismatch was not statistically significantly different between the groups (p = 0.364). The 30-day mortality was 0%, whereas the 1-year mortality was 4.3%, with no difference between the groups. An increase in preoperative creatinine was associated with higher risk of death (hazard ratio 1.206, 95% confidence interval 1.025 to 1.418, p = 0.02), whereas gender was not. Kaplan-Meier survival estimates (Log rank, p = 0.768) and cumulative incidence of stroke readmission (p = 0.842) were similar in both groups. In conclusion, the outcomes of TAVR in SAAs do not differ by gender, with safety and efficacy evident in men and women.

Central versus peripheral cannulation for acute type A aortic dissection: A meta-analysis of over 14,000 patients.

OBJECTIVE: The optimal cannulation strategy for patients with acute type A aortic dissections (ATAAD) is unclear. METHODS: A systematic search was performed to identify all studies comparing aortic and non-aortic cannulation in patients undergoing ATAAD repair. The primary endpoint was overall survival. The secondary endpoints were operative mortality, postoperative stroke, renal failure, renal replacement therapy, paraplegia, and mesenteric ischemia. Pooled meta-analyses with aggregated and reconstructed time-to-event data were performed. RESULTS: Twenty-three studies were included (aortic: 3904; non-aortic: 10,719). Ten-year overall survival was 61.1 â€‹% and 58.4 â€‹% for aortic and non-aortic cannulation, respectively (HR 1.07; 95 â€‹% CI 0.92-1.25; p â€‹= â€‹0.38). No statistically significant difference was observed for operative mortality (p â€‹= â€‹0.10), stroke (p â€‹= â€‹0.89), renal failure (p â€‹= â€‹0.83), or renal replacement therapy (p â€‹= â€‹0.77). CONCLUSION: Patients undergoing surgery for ATAAD can undergo aortic cannulation with similar outcomes to those who undergo non-aortic cannulation.