Cerebral Embolic Protection during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) for the treatment of aortic stenosis can lead to embolization of debris. Capture of debris by devices that provide cerebral embolic protection (CEP) may reduce the risk of stroke. METHODS: We randomly assigned patients with aortic stenosis in a 1:1 ratio to undergo transfemoral TAVR with CEP (CEP group) or without CEP (control group). The primary end point was stroke within 72 hours after TAVR or before discharge (whichever came first) in the intention-to-treat population. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed. A neurology professional examined all the patients at baseline and after TAVR. RESULTS: A total of 3000 patients across North America, Europe, and Australia underwent randomization; 1501 were assigned to the CEP group and 1499 to the control group. A CEP device was successfully deployed in 1406 of the 1489 patients (94.4%) in whom an attempt was made. The incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group (2.3% vs. 2.9%; difference, -0.6 percentage points; 95% confidence interval, -1.7 to 0.5; P = 0.30). Disabling stroke occurred in 0.5% of the patients in the CEP group and in 1.3% of those in the control group. There were no substantial differences between the CEP group and the control group in the percentage of patients who died (0.5% vs. 0.3%); had a stroke, a transient ischemic attack, or delirium (3.1% vs. 3.7%); or had acute kidney injury (0.5% vs. 0.5%). One patient (0.1%) had a vascular complication at the CEP access site. CONCLUSIONS: Among patients with aortic stenosis undergoing transfemoral TAVR, the use of CEP did not have a significant effect on the incidence of periprocedural stroke, but on the basis of the 95% confidence interval around this outcome, the results may not rule out a benefit of CEP during TAVR. (Funded by Boston Scientific; PROTECTED TAVR ClinicalTrials.gov number, NCT04149535.).

Transcatheter heart valve explant with infective endocarditis-associated prosthesis failure and outcomes: the EXPLANT-TAVR international registry.

BACKGROUND AND AIMS: Surgical explantation of transcatheter heart valves (THVs) is rapidly increasing, but there are limited data on patients with THV-associated infective endocarditis (IE). This study aims to assess the outcomes of patients undergoing THV explant for IE. METHODS: All patients who underwent THV explant between 2011 and 2022 from 44 sites in the EXPLANT-TAVR registry were identified. Patients with IE as the reason for THV explant were compared to those with other mechanisms of bioprosthetic valve dysfunction (BVD). RESULTS: A total of 372 patients from the EXPLANT-TAVR registry were included. Among them, 184 (49.5%) patients underwent THV explant due to IE and 188 (50.5%) patients due to BVD. At the index transcatheter aortic valve replacement, patients undergoing THV explant for IE were older (74.3 ± 8.6 vs. 71 ± 10.6 years) and had a lower Society of Thoracic Surgeons risk score [2.6% (1.8-5.0) vs. 3.3% (2.1-5.6), P = .029] compared to patients with BVD. Compared to BVD, IE patients had longer intensive care unit and hospital stays (P < .05) and higher stroke rates at 30 days (8.6% vs. 2.9%, P = .032) and 1 year (16.2% vs. 5.2%, P = .010). Adjusted in-hospital, 30-day, and 1-year mortality was 12.1%, 16.1%, and 33.8%, respectively, for the entire cohort, with no significant differences between groups. Although mortality was numerically higher in IE patients 3 years postsurgery (29.6% for BVD vs. 43.9% for IE), Kaplan-Meier analysis showed no significant differences between groups (P = .16). CONCLUSIONS: In the EXPLANT-TAVR registry, patients undergoing THV explant for IE had higher 30-day and 1-year stroke rates and longer intensive care unit and hospital stays. Moreover, patients undergoing THV explant for IE had a higher 3-year mortality rate, which did not reach statistical significance given the relatively small sample size of this unique cohort and the reduced number of events.

Surgical debranching versus branched endografting in zone 2 thoracic endovascular aortic repair.

BACKGROUND: Left subclavian artery (LSA) revascularization has been recommended for patients undergoing elective thoracic endovascular aortic repair (TEVAR) with a proximal zone 2 landing requiring coverage of the LSA. The clinical standard of care remains surgical LSA revascularization. However, recently, the feasibility of using branched endografts has been demonstrated. We compared the perioperative and mid-term outcomes of these approaches. METHODS: We performed a retrospective review of consecutive patients who underwent TEVAR with a proximal zone 2 landing at a single center from 2014 to 2020. The patients were divided into cohorts for comparison: those who underwent surgical revascularization (SR-TEVAR group) and those who underwent thoracic branched endografting with an investigational device (TBE group). Those patients who did not undergo LSA revascularization were excluded. Perioperative outcomes, including procedural success, death, stroke, limb ischemia, and length of stay, were compared. Kaplan-Meier survival curves were compared using the log-rank test. The cumulative incidence of device-related endoleak (types I and III) and device-related reintervention, accounting for death as a competing hazard, were compared using the Fine-Gray test. RESULTS: A total of 55 patients were included: 31 (56%) in the SR-TEVAR group and 24 (44%) in the TBE group. The preoperative demographics and comorbidities were similar between the two groups. Procedural success was 100% in both cohorts, with no periprocedural strokes or left upper extremity ischemic events. One operative or 30-day death (TBE, 4.2%; vs SR-TEVAR, 3.2%; P = .99) occurred in each cohort. The total operative time (TBE, 203 ± 79 minutes; vs SR-TEVAR, 250 ± 79 minutes; P = .03) and total length of stay (TBE, 5.2 ± 3.6 days; vs SR-TEVAR, 9.9 ± 7.2 minutes; P = .004) were both significantly shorter in the TBE group. No difference was found in mid-term survival (log-rank test, P = .50) nor the cumulative incidence of device-related endoleak (Fine-Gray test, P = .51) or reintervention (Fine-Gray test, P = .72). No occlusions of the TBE graft or surgical bypass or transpositions had occurred after a mean follow-up of 28 ± 16 and 34 ± 24 months, respectively. CONCLUSIONS: TBE can be performed with procedural success rate and safety profile comparable to those of TEVAR with surgical revascularization, with a decreased total length of stay, for patients requiring proximal zone 2 coverage. The mid-term outcomes for each approach were also similar. Prospective, randomized comparisons of these techniques are warranted.

Impact of preoperative Impella support on destination left ventricular assist device outcomes.

BACKGROUND: Although left ventricular assist device (LVAD) implantation is associated with improved heart failure survival, the impact of pre-implantation Impella support on outcomes is unknown. We undertook this study to evaluate the impact of preoperative Impella support on LVAD outcomes. METHODS: We conducted a retrospective review of all Heartmate 3 LVAD implants. Primary stratification was by the need for preoperative Impella support with the 5.0/5.5 device. Longitudinal survival was assessed by the Kaplan-Meier method. Multivariable Cox proportional hazards regression models were developed to evaluate mortality. Secondary outcomes included changes in laboratory values during Impella support. RESULTS: From 2017 to 2021, 87 patients underwent LVAD implantation. Sixteen were supported with a single inotrope, 36 with dual inotropes, 27 with Impella, and 3 with extracorporeal membrane oxygenation (ECMO). When stratified by the need for Impella, there was no difference in survival at 30-days (98.3 [88.2-99.8]% vs. 96.3 [76.5-99.5]%, p = .59), 1-year (91.0 [79.8-96.2] vs. 74.9 [51.7-88.2], p = .10), or at 2 years (87.9 [74.3-94.5] vs. 74.9 [51.7-88.2], p = .15). On multivariable modeling, the need for preoperative Impella was not associated with an increased hazard of 1-year (1.24 [0.23-6.73], p = .81) or 2-year mortality (1.05 [0.21-5.19], p = .95). After 7 (5-10) days of Impella support, recipient creatinine (p < .01), creatinine clearance (p = .02), and total bilirubin (p = .053) improved and lactic acidosis resolved (p < .01). CONCLUSIONS: Preoperative Impella support is not associated with increased short or long-term mortality but is associated with improved renal and hepatic function as well as total body perfusion before LVAD implantation.

Outcomes of aortic root enlargement during isolated aortic valve replacement.

OBJECTIVES: Aortic root enlargement (ARE) lowers the risk of patient prosthesis mismatch after surgical aortic valve replacement (SAVR) in patients with small annular size. Whether ARE is associated with increased operative mortality is controversial. This study compares the early and intermediate outcomes in patients undergoing SAVR with and without ARE. METHODS: All patients undergoing isolated SAVR with and without ARE from 2015 to 2020 were analyzed. Propensity-matching was used to adjust for possible confounding variables. Kaplan-Meier analysis and log-rank test were used to estimate and compare overall outcomes and survival in the study cohorts. RESULTS: Among 868 isolated SAVRs, ARE was performed in 54 (6.2%) patients. Before matching, mean age was similar but female sex (67.4% vs. 29.6%; SD: -0.82) and previous AVR (18.9% vs. 3.9%; SD: -0.48) were more common in patients undergoing SAVR + ARE versus SAVR alone. A bovine pericardial patch was used for 81.5% (44 of 54) of ARE, with a Dacron patch in the rest. After propensity matching, the average cardiopulmonary bypass (138.2 ± 34.9 vs. 102.9 ± 33.0 min; p < 0.01) and cross-clamp times (113.8 ± 26.7 vs. 83.0 ± 28.4 min; p < 0.01) were longer in the SAVR + ARE group. There were no significant differences in postoperative stroke, new-onset dialysis, pacemaker placement, reoperation for bleeding, length of hospital stay, or 30-day readmission. Thirty-day mortality (0% vs. 0.6%, p = 1.0) and 5-year survival (96.3% vs. 95.7%, p = 0.86) were also similar. CONCLUSIONS: ARE during surgical AVR can be safely performed without an increase in complications with excellent early and intermediate-term survival.

Assessing the risk of an anomalous circumflex artery using balloon aortic valvuloplasty prior to transcatheter aortic valve replacement.

Anomalous origin of the left circumflex coronary artery from the right sinus of Valsalva or proximal right coronary artery (RCA) is a well-known anatomic variation. Although the condition is usually benign, there is risk for compression of the anomalous artery by a prosthetic valve in patients undergoing aortic valve replacement (AVR). In more recent years, balloon aortic valvuloplasty (BAV) has been performed prior to transcatheter aortic valve replacement (TAVR) to serve as a diagnostic tool in the evaluation of symptom relief and procedural risks prior to definitive therapy with TAVR. However, the literature regarding BAV utilization in the assessment of coronary artery anomalies prior to TAVR is scarce. Our case illustrates the importance of performing preoperative BAV to assess the safety of a TAVR procedure in patients with coronary anomalies. Herein, we present a case of a patient who underwent BAV with selective angiography of her anomalous circumflex artery. During balloon inflation, the anomalous circumflex artery was transiently occluded, with complete resolution with balloon deflation. Given these findings, the patient was deemed to be unsuitable for TAVR and offered surgical AVR. This case demonstrates that patients with anomalous coronary circulation may require BAV with selective angiography to fully evaluate risk of coronary occlusion with TAVR.

Identification of NEK3 Kinase Threonine 165 as a Novel Regulatory Phosphorylation Site That Modulates Focal Adhesion Remodeling Necessary for Breast Cancer Cell Migration.

Accumulating evidence supports a role for prolactin (PRL) in the development and progression of human breast cancer. Although PRL is an established chemoattractant for breast cancer cells, the precise molecular mechanisms of how PRL regulates breast cancer cell motility and invasion are not fully understood. PRL activates the serine/threonine kinase NEK3, which was reported to enhance breast cancer cell migration, invasion, and the actin cytoskeletal reorganization necessary for these processes. However, the specific mechanisms of NEK3 activation in response to PRL signaling have not been defined. In this report, a novel PRL-inducible regulatory phosphorylation site within the activation segment of NEK3, threonine 165 (Thr-165), was identified. Phosphorylation at NEK3 Thr-165 was found to be dependent on activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway using both pharmacological inhibition and siRNA-mediated knockdown approaches. Strikingly, inhibition of phosphorylation at NEK3 Thr-165 by expression of a phospho-deficient mutant (NEK3-T165V) resulted in increased focal adhesion size, formation of zyxin-positive focal adhesions, and reorganization of the actin cytoskeleton into stress fibers. Concordantly, NEK3-T165V cells exhibited migratory defects. Together, these data support a modulatory role for phosphorylation at NEK3 Thr-165 in focal adhesion maturation and/or turnover to promote breast cancer cell migration.

Congenital anomalies of the aortic arch in acute type-a aortic dissection: implications for monitoring, perfusion strategy, and surgical repair.

OBJECTIVE: To assess whether management of acute Stanford type-A aortic dissection differs in patients with congenital anomalies of the aortic arch compared with standard institutional practice. DESIGN: Retrospective analysis of all consecutive patients from 2001 through 2011. SETTING: Quaternary referral center for surgical management of thoracic aortic disease. PARTICIPANTS: All patients with arch anomalies who underwent surgery for acute Stanford type-A aortic dissection during the study period (n = 43). INTERVENTIONS: Surgical management, anesthetic monitoring, and perfusion strategy were analyzed in a retrospective fashion. No new interventions were undertaken as part of this study. MEASUREMENTS AND MAIN RESULTS: Management differed most in patients with an aberrant right subclavian artery (n = 5), because the institutional standard of right axillary artery cannulation with left upper extremity arterial pressure monitoring was not possible. In patients with one of two "bovine" arch patterns (n = 32), management differed in the conduct of selective antegrade cerebral perfusion, which could include clamping above or below the takeoff of the left common carotid artery (and, therefore, produced unilateral or bilateral antegrade cerebral perfusion). All patients with a connective tissue disorder exhibited a bovine arch pattern. Management of patients with a right arch (n = 3) reflected the opposite of management for normal anatomy (for patients with traditional mirror-image branching) or opposite that of the aberrant right subclavian group (for patients who had a corresponding aberrant left subclavian artery). CONCLUSIONS: Rational management reflected the anatomic variations observed. These results support the importance of interdisciplinary planning, especially in an emergency, to optimize outcome.

Midterm durability of valve-sparing root replacement in bicuspid and tricuspid aortic valves.

Background: Among patients with bicuspid aortic valves (BAV) who are potential candidates for valve-sparing root replacement (VSRR), the long-term durability of this technique is not well understood. This study aimed to compare the clinical and echocardiographic outcomes of VSRR in those with BAV and tricuspid aortic valve (TAV) morphology. Methods: This was a retrospective analysis of patients who underwent VSRR between 2007 and 2021 at a single center. Kaplan-Meier and log-rank analysis were used to estimate and compare freedom from mortality, progression to >2+ aortic insufficiency (AI), and reoperation between groups (BAV vs TAV). Preoperative and postoperative echocardiographic data were collected and assessed for temporal changes in mixed-effect models. Results: A total of 185 patients (BAV, n = 52, 28.1%; TAV, n = 133, 71.9%) underwent VSRR. At baseline, BAV patients were younger (42.4 ± 11.6 vs 52.3 ± 12.6 years; P < 0.01) and had more severe AI (47.9% vs 27.0%; P = 0.02). Average cardiopulmonary bypass and cross-clamp times were similar. There were no differences in rates of postoperative complications, intensive care unit or hospital days, or 30-day readmission. TAV patients' 1-, 5-, and 8-year survival rates were 99.2% [95% CI 97.8-100], 96.7% [93.5-99.9%], and 92.2% [85.6-99.3%], respectively. Overall, there were no differences between groups regarding freedom from mortality (P = 0.18), reoperation (P = 0.51), or recurrent >2+ AI (P = 0.97). . Conclusions: VSRR can be safely performed on patients with BAV and TAV morphology, yielding similar midterm freedom from mortality, recurrent >2+ AI, and reoperation. This technique should be considered in carefully selected patients with aortic root pathology and BAV anatomy when performed at experienced centers.

Hospital and surgeon surgical valvar volume and survival after multivalve cardiac surgery in Medicare beneficiaries.

OBJECTIVE: Long-term outcomes after multivalve cardiac surgery remain underevaluated. METHODS: Medicare administrative claims from 2008 to 2019 identified beneficiaries undergoing multivalve surgery. Operative characteristics were doubly adjudicated using International Classification of Diseases and Current Procedural Technology codes. A multivariable flexible parametric model evaluated predictors of survival; regression standardization was performed to predict standardized survival probabilities (SSPs) at varying percentiles of annual valvar volume. RESULTS: Of 476,092 cardiac surgeries involving the aortic (AVS), mitral (MVS), or tricuspid (TVS) valve, 63,083 (13.3%) were identified as involving multi-valve surgery, including 22,884 MVS/TVS, 30,697 AVS/MVS, 3443 AVS/TVS, and 6059 AVS/MVS/TVS. Surgery occurred at 1157 hospitals by 2922 surgeons. Annual valvar volume (total AVS/MVS/TVS) was tallied for surgeons and hospitals. Median survival varied substantially by type of multivalve surgery: 8.09 (95% CI: 7.90-8.24) years in MVS/TVS, 6.65 (95% CI: 6.49-6.81) years in AVS/MVS, 5.77 (95% CI: 5.37-6.13) years in AVS/TVS, and 6.02 (95% CI: 5.64-6.38) years in AVS/MVS/TVS. SSPs were calculated across combined hospital/surgeon volume percentiles; the median SSP increased with increasing percentile of combined hospital/surgeon volume: 5th percentile, 5.77 (95% CI: 5.58-5.98), 25th percentile, 6.18 (95% CI: 6.07-6.28), 50th percentile, 6.56 (95% CI: 6.44-6.68), 75%th percentile, 6.86 (95% CI: 6.75-6.97), and 95th percentile, 7.58 (95% CI: 7.34-7.83) years, respectively. CONCLUSIONS: Survival varied significantly by type of multivalve surgery, worsened with addition of concomitant interventions and improved substantially with increasing annual hospital and surgeon volume. Hospital volume was associated with an improved early hazard for death that abated beyond 3 months post surgery, while surgeon volume was associated with an improved hazard for death that persisted even beyond the first postoperative year. Consideration should be given to referring multivalve cases to high-volume hospitals and surgeons.

Five-Year Outcomes of Measured and Predicted Prosthesis-Patient Mismatch following Transcatheter Aortic Valve Implantation.

Data on the long-term outcomes of prosthesis patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI) remain controversial. This study aimed to investigate the incidence and clinical outcomes of measured PPM (PPMM) and predicted PPM (PPMP) in patients who underwent TAVI. This is a retrospective analysis of 3,016 patients who underwent TAVI at a large health care system between 2012 and 2021. Effective orifice area indexed to body surface area (EOAi) was measured at discharge using the continuity equation. EOAi was predicted according to the published predictive tables for each model and size of the valve. Primary end point was 5-year survival rate. Mean age was 80 years, and 55.6% were male. The mean Society of Thoracic Surgeons risk score was 4.66%. 74.9% of patients received a balloon-expandable valve (BEV), and 25.1% received a self-expanding valve (SEV). The incidence of severe PPM was markedly lower when defined by predicted versus measured EOAi (0.8% vs 6.3%, p <0.001) and when assessed in SEV versus BEV (5.3% vs 6.6%, p = 0.02). Neither severe PPMp nor severe PPMM was associated with 5-year mortality (hazard ratio 1.26, 95% confidence interval 0.96 to 1.66, p = 0.095; hazard ratio 1.03, 95% confidence interval 0.42 to 2.49, p = 0.954, respectively), irrespective of the presence of high residual pressure gradient. Neither BEV nor SEV was associated with an increased 5-year mortality, irrespective of PPM definition or severity. In this large health care system analysis, neither severe PPMP nor severe PPMM was associated with 5-year all-cause mortality. There was no difference between BEV and SEV in terms of mortality, irrespective of the definition or severity of PPM.

Race, neighborhood disadvantage, and survival of Medicare beneficiaries after aortic valve replacement and concomitant coronary artery bypass grafting.

BACKGROUND: Race, neighborhood disadvantage, and the interaction between these 2 social determinants of health remain poorly understood with regards to survival after aortic valve replacement with concomitant coronary artery bypass grafting (AVR+CABG). METHODS: Weighted Kaplan-Meier survival analyses and Cox proportional hazards modeling were used to evaluate the association between race, neighborhood disadvantage, and long-term survival in 205,408 Medicare beneficiaries undergoing AVR+CABG from 1999 to 2015. Neighborhood disadvantage was measured using the Area Deprivation Index, a broadly validated ranking of socioeconomic contextual disadvantage. RESULTS: Self-identified race was 93.9% White and 3.2% Black. Residents of the most disadvantaged quintile of neighborhoods included 12.6% of all White beneficiaries and 40.0% of all Black beneficiaries. Black beneficiaries and residents of the most disadvantaged quintile of neighborhoods had more comorbidities compared with White beneficiaries and residents of the least disadvantaged quintile of neighborhoods, respectively. Increasing neighborhood disadvantage linearly increased the hazard for mortality for Medicare beneficiaries of White but not Black race. Residents of the most and least disadvantaged neighborhood quintiles had weighted median overall survival of 93.0 and 82.1 months, respectively, a significant difference (P < .001 by Cox test for equality of survival curves). Black and White beneficiaries had weighted median overall survival of 93.4 and 90.6 months, respectively, a nonsignificant difference (P = .29 by Cox test for equality of survival curves). A statistically significant interaction between race and neighborhood disadvantage was noted (likelihood ratio test P = .0215) and had implications on whether Black race was associated with survival. CONCLUSIONS: Increasing neighborhood disadvantage was linearly associated with worse survival after combined AVR+CABG in White but not Black Medicare beneficiaries; race, however, was not independently associated with postoperative survival.

Outcomes of redo operations after the Ross procedure.

BACKGROUND: The Ross procedure is not commonly performed, owing to the procedural complexity and the risk of autograft and/or homograft reoperation. This study examined outcomes of patients undergoing Ross reinterventions at a dedicated Ross center. METHODS: We retrospectively reviewed 225 consecutive patients who underwent a Ross procedure between 1994 and 2019. Index and redo operation characteristics and outcomes were compared between patients with and those without redo operations. Multivariate analysis was used to identify independent predictors of Ross-related reinterventions. Survival was estimated with Kaplan-Meier analysis. RESULTS: Sixty-six patients (29.3%) required redo Ross surgery, 41 patients (18.2%) underwent autograft reoperation only, 8 patients (3.6%) had a homograft reintervention, and 17 patients (7.6%) had both autograft and homograft reoperations (12 as a combined procedure and 5 as sequential procedures). The mean time to reintervention was 11 ± 6 years for autograft reoperations and 12 ± 7 years for homograft reoperations. Patients who underwent Ross-related reinterventions were younger (mean, 38 ± 11 years vs 43 ± 11 years; P < .01) and had a higher rate of New York Heart Association class III/IV (56% vs 38%; P = .02) at the index Ross procedure. Most patients undergoing autograft reintervention had aortic insufficiency and/or aneurysm (98.2%; 57 of 58). The primary reason for homograft reintervention was pulmonary stenosis (92%; 23 of 25). The operative mortality of Ross reintervention was 1.5% (1 of 66). Survival at 15 years was similar in patients who required a redo operation and those who did not (91.2% vs 93.9%; P = .23). CONCLUSIONS: Ross reinterventions can be performed safely and maintain patients at the normal life expectancy restored by the index Ross procedure up to 15 years at experienced centers.

Outcomes of the Ross procedure in patients older versus younger than 50 years old.

OBJECTIVES: The Ross procedure is traditionally considered for young adult patients with aortic valve disease. This study compares long-term outcomes of patients undergoing the Ross procedure who are ≥50 and <50-years old. METHODS: Data were collected from 225 patients undergoing Ross procedure at a single centre from 1994 to 2019. Patients were categorized into younger (<50-years old; n = 156) and older (≥50-years old; n = 69) cohorts. Baseline demographics clinical outcomes were compared. RESULTS: The mean age was 36 ± 8.1 and 55 ± 4.2 years in the younger and older cohort, respectively. Both groups were predominantly male (58.5% vs 69.6%; P = 0.59). The younger group had a higher rate of aortic insufficiency (51% vs 26.1%; P < 0.01), and bicuspid aortic valve (81.4% vs 58.0%; P < 0.01). Aortic stenosis was more prevalent in the older cohort (25.6% vs 58.0%; P < 0.01). Operative mortality was acceptable in both groups (1.3% vs 4.3%; P = 0.15). Survival up to 10 years was not statistically different between 2 groups (96.2% vs 91.3% P = 0.16), whereas survival up to 15 years for younger patients was significantly higher (94.9% vs 85.5%; P = 0.03). After non-cardiac related deaths were excluded, survival up to 15 years (98.7% vs 91.3%; P = 0.02) was significantly lower than younger patients. In both groups, survival after the Ross procedure was similar to the age- and sex-matched US population. CONCLUSIONS: Survival up to 10 years after Ross procedure were similar, but up to 15 years was significantly higher in younger patients. The Ross procedure restored patients from both groups to expected survival. Our results suggest that at experienced centres, the Ross procedure is a safe and reasonable option for patients who are 50 years and older.

30-Day Clinical Outcomes of a Self-Expanding Transcatheter Aortic Valve: The International PORTICO NG Study.

BACKGROUND: The self-expanding, intra-annular Navitor (Abbott Structural Heart) valve includes an outer cuff to reduce paravalvular leak (PVL) and large stent cells for future coronary access. OBJECTIVES: The purpose of the PORTICO NG (Evaluation of the Portico NG [Next Generation] Transcatheter Aortic Valve in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis) study is to evaluate the safety and effectiveness of the Navitor valve in patients with symptomatic, severe aortic stenosis who are at high or extreme surgical risk. METHODS: PORTICO NG is a prospective, multicenter, global study with follow-up at 30 days, 1 year, and annually through 5 years. The primary endpoints are all-cause mortality and moderate or greater PVL at 30 days. Valve Academic Research Consortium-2 events and valve performance are assessed by an independent clinical events committee and echocardiographic core laboratory. RESULTS: A total of 260 subjects were treated at 26 clinical sites across Europe, Australia, and the United States between September 2019 and August 2022. The mean age was 83.4 ± 5.4 years, 57.3% were female, and the average Society of Thoracic Surgeons score was 3.9% ± 2.1%. At 30 days, the rate of all-cause mortality was 1.9%, and no subjects had moderate or greater PVL. The rate of disabling stroke was 1.9%, life-threatening bleeding was 3.8%, stage 3 acute kidney injury was 0.8%, major vascular complications were 4.2%, and new permanent pacemaker implantation was 19.0%. Hemodynamic performance included a mean gradient of 7.4 ± 3.5 mm Hg and an effective orifice area of 2.00 ± 0.47 cm2. CONCLUSIONS: The Navitor valve is safe and effective for the treatment of subjects with severe aortic stenosis who are at high or greater risk for surgery, which is supported by low rates of adverse events and PVL. (Evaluation of the Portico NG [Next Generation] Transcatheter Aortic Valve in High and Extreme Risk Patients With Symptomatic Severe Aortic Stenosis [PORTICO NG]; NCT04011722).

Challenges and Future Directions in Redo Aortic Valve Reintervention After Transcatheter Aortic Valve Replacement Failure.

Transcatheter aortic valve replacement (TAVR) is increasingly being performed in younger and lower surgical risk patients. Reintervention for failed transcatheter heart valves will likely increase in the future as younger patients are expected to outlive the initial bioprosthesis. While redo-TAVR has emerged as an attractive and less invasive alternative to surgical explantation (TAVR-explant) to treat transcatheter heart valve failure, it may not be feasible in all patients due to the risk of coronary obstruction and impaired coronary access. Conversely, TAVR-explant can be offered to most patients who are surgical candidates, but the reported outcomes have shown high mortality and morbidity. This review provides the latest evidence, current challenges, and future directions on redo-TAVR and TAVR-explant for transcatheter heart valve failure, to guide aortic valve reintervention and facilitate patients' lifetime management of aortic stenosis.

Effect of Preincisional Liposomal Bupivacaine Sternal Blockade on Poststernotomy Opioid Use.

BACKGROUND: Prolonged and excessive opioid use in the postoperative setting is associated with multiple complications. The use of regional analgesia may reduce postoperative opioid use. METHODS: In a placebo-controlled, double-blinded trial patients undergoing sternotomy were randomly assigned in a 1:1 ratio to receive either a liposomal bupivacaine parasternal block or a normal saline parasternal injection. The primary endpoint was total morphine milligram equivalents (MMEs) used in the immediate 72-hour postoperative period. Secondary endpoints were intraoperative opioid use, pain scores, time to reach recovery milestones, and incidence of postoperative complications. RESULTS: Twenty-five patients received a normal saline injection, and 27 patients received an anesthetic sternal block. Randomization achieved excellent balance in demographics and comorbidities between the groups. Total postoperative opioid requirements at 72 hours were similar between the treatment and control groups (25.8 ± 10.4 vs 29.4 ± 16.3 MMEs, P = .60). Intraoperative opioid requirements were also similar between the 2 groups (124.8 ± 222.5 vs 114.9 ± 148.0 MMEs, P = .86). Length of stay in the intensive care unit (3.4 ± 2.5 vs 3.5 ± 2.6 days, P = .86) and hospital (8.7 ± 5.0 vs 7.5 ± 3.0 days, P = .45), time until return of bowel function (3.7 ± 1.4 vs 3.3 ± 1.4 days, P = .42), incidence of postoperative atrial fibrillation (24% vs 22.2%, P = .88), and incidence of nausea (24% vs 33.3%, P = .46) were similar. CONCLUSIONS: Preincisional sternal blockade with liposomal bupivacaine did not reduce the amount of opioid medication administered to patients in the first 72 hours after sternotomy.

Claudin 4 Is differentially expressed between ovarian cancer subtypes and plays a role in spheroid formation.

Claudin 4 is a cellular adhesion molecule that is frequently overexpressed in ovarian cancer and other epithelial cancers. In this study, we sought to determine whether the expression of claudin 4 is associated with outcome in ovarian cancer patients and may be involved in tumor progression. We examined claudin 4 expression in ovarian cancer tissues and cell lines, as well as by immunohistochemical staining of tissue microarrays (TMAs; n = 500), spheroids present in patients' ascites, and spheroids formed in vitro. Claudin 4 was expressed in nearly 70% of the ovarian cancer tissues examined and was differentially expressed across ovarian cancer subtypes, with the lowest expression in clear cell subtype. No association was found between claudin 4 expression and disease-specific survival in any subtype. Claudin 4 expression was also observed in multicellular spheroids obtained from patients' ascites. Using an in vitro spheroid formation assay, we found that NIH:OVCAR5 cells treated with shRNA against claudin 4 required a longer time to form compact spheroids compared to control NIH:OVCAR5 cells that expressed high levels of claudin 4. The inability of the NIH:OVCAR5 cells treated with claudin 4 shRNA to form compact spheroids was verified by FITC-dextran exclusion. These results demonstrate a role for claudin 4 and tight junctions in spheroid formation and integrity.

Long-term outcomes of the Ross procedure in adults.

BACKGROUND: The optimal aortic valve replacement for young and middle-aged adults remains elusive. Although several high-volume international centers and surgeons have demonstrated excellent long-term results with the pulmonary autograft (Ross procedure) in adult patients, current guidelines from the United States do not favor this technique. We evaluated long-term clinical and echocardiographic outcomes of adult patients undergoing the Ross procedure at our center. METHODS: A retrospective review of 225 consecutive adult patients undergoing the Ross procedure was completed. Kaplan-Meier analysis was performed to evaluate overall survival, which was then compared to an age- and sex-matched general population with the log-rank test. Accounting for death as a competing hazard, the cumulative incidence of reintervention and autograft or homograft dysfunction were estimated over the long-term. RESULTS: Mean age was 42±11 years, and 62 (28%) patients were at least 50 years old. A bicuspid aortic valve was present in 179 (80%) patients. The most common indications for surgery were aortic insufficiency (n=94, 43%), aortic stenosis (n=81, 36%), and mixed etiology (n=46, 21%). In-hospital mortality was 0.9%. Overall survival (with 95% confidence intervals) at 1-, 10- and 20-year was 97.8% (95.9-99.7%), 94.2% (91.0-97.4%), and 81.3% (74.8-88.3%), respectively. Overall survival approximated that of the general population (log-rank P=0.32). The cumulative incidence (with 95% confidence intervals) of any autograft or homograft reintervention at 10-, 15-, and 20-year was 16% (12-20%), 28% (21-35%), and 45% (36-54%), respectively. CONCLUSIONS: The Ross procedure restores a normal life expectancy to young and middle-aged adults with severe aortic valve disease. The need for reintervention increases steadily during the second decade after the Ross procedure, but less than half of patients require any reintervention for up to 20-year.