Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

BACKGROUND AND OBJECTIVES: Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT. METHODS: Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT. RESULTS: Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up. DISCUSSION: Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.

Heart Brain Clinic: An Integrated Approach to Stroke Care.

Background and Objectives: Multidisciplinary clinics have been shown to improve care. Patients with patent foramen ovale (PFO)-associated stroke need evaluation by cardiology and neurology specialists. We report our experience creating a multidisciplinary Structural Heart Brain Clinic (HBC) with a focus on patients with PFO-associated stroke. Methods: Demographic and clinical data were retrospectively collected for patients with PFO-associated ischemic stroke. Patients with PFO-associated stroke were divided into a standard care group and Heart Brain Clinic group for analysis. Outcome measures included time from stroke to PFO closure and number of clinic visits before decision regarding closure. Nonparametric analysis evaluated differences in median time to visit and clinical decision, while the chi square analysis compared differences in categorical variables between groups. Results: From February 2017 to December 2021, 120 patients were evaluated for PFO-associated stroke. The Structural HBC began in 12/2018 with coordination between Departments of Neurology and Cardiology. For this analysis, 41 patients were considered in the standard care group and 79 patients in the HBC group. During data analysis, 107 patients had received recommendations about PFO closure. HBC patients required fewer clinic visits (p = 0.001) before decision about closure; however, among patients who underwent PFO closure, there was no significant difference in weeks from stroke to PFO closure. Clinicians were more likely to recommend against PFO closure among patients seen in HBC compared with those seen in standard care (p = 0.021). Discussion: Our data demonstrate that a multidisciplinary, patient-centered approach to management of patients with PFO-associated ischemic stroke is feasible and may improve the quality of care in this younger patient population. The difference in recommendation to not pursue PFO closure between groups may reflect selection and referral bias. Additional work is needed to determine whether this approach improves other aspects of care and outcomes.

Association of Atrial Septal Aneurysm and Shunt Size With Stroke Recurrence and Benefit From Patent Foramen Ovale Closure.

Importance: The Patent Foramen Ovale (PFO)-Associated Stroke Causal Likelihood classification system combines information regarding noncardiac patient features (vascular risk factors, infarct topography) and PFO features (shunt size and presence of atrial septal aneurysm [ASA]) to classify patients into 3 validated categories of responsiveness to treatment with PFO closure. However, the distinctive associations of shunt size and ASA, alone and in combination, have not been completely delineated. Objective: To evaluate the association of PFO closure with stroke recurrence according to shunt size and/or the presence of an ASA. Design, Setting, and Participants: Pooled individual patient data from 6 randomized clinical trials conducted from February 2000 to October 2017 that compared PFO closure with medical therapy. Patients in North America, Europe, Australia, Brazil, and South Korea with PFO-associated stroke were included. Analysis was completed in January 2022. Exposures: Transcatheter PFO closure plus antithrombotic therapy vs antithrombotic therapy alone, stratified into 4 groups based on the combination of 2 features: small vs large PFO shunt size and the presence or absence of an ASA. Main Outcomes and Measures: Recurrent ischemic stroke. Results: A total of 121 recurrent ischemic strokes occurred in the pooled 3740 patients (mean [SD] age, 45 [10] years; 1682 [45%] female) during a median (IQR) follow-up of 57 (23.7-63.8) months. Treatment with PFO closure was associated with reduced risk for recurrent ischemic stroke (adjusted hazard ratio [aHR], 0.41 [95% CI, 0.28-0.60]; P < .001). The reduction in hazard for recurrent stroke was greater for patients with both a large shunt and an ASA (aHR, 0.15 [95% CI, 0.06-0.35]) than for large shunt without ASA (aHR, 0.27 [95% CI, 0.14-0.56]), small shunt with ASA (aHR, 0.36 [95% CI, 0.17-0.78]), and small shunt without ASA (aHR, 0.68 [95% CI, 0.41-1.13]) (interaction P = .02). At 2 years, the absolute risk reduction of recurrent stroke was greater (5.5% [95% CI, 2.7-8.3]) in patients with large shunt and ASA than for patients in the other 3 categories (1.0% for all). Conclusions and Relevance: Patients with both a large shunt and an ASA showed a substantially greater beneficial association with PFO closure than patients with large shunt alone, patients with small shunt and ASA, and patients with neither large shunt nor ASA. These findings, combined with other patient features, may inform shared patient-clinician decision-making.

Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data From Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke.

Importance: Patent foramen ovale (PFO)-associated strokes comprise approximately 10% of ischemic strokes in adults aged 18 to 60 years. While device closure decreases stroke recurrence risk overall, the best treatment for any individual is often unclear. Objective: To evaluate heterogeneity of treatment effect of PFO closure on stroke recurrence based on previously developed scoring systems. Design, Setting, and Participants: Investigators for the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) Consortium pooled individual patient data from all 6 randomized clinical trials that compared PFO closure plus medical therapy vs medical therapy alone in patients with PFO-associated stroke, and included a total of 3740 participants. The trials were conducted worldwide from 2000 to 2017. Exposures: PFO closure plus medical therapy vs medical therapy alone. Subgroup analyses used the Risk of Paradoxical Embolism (RoPE) Score (a 10-point scoring system in which higher scores reflect younger age and the absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) Classification System, which combines the RoPE Score with high-risk PFO features (either an atrial septal aneurysm or a large-sized shunt) to classify patients into 3 categories of causal relatedness: unlikely, possible, and probable. Main Outcomes and Measures: Ischemic stroke. Results: Over a median follow-up of 57 months (IQR, 24-64), 121 outcomes occurred in 3740 patients. The annualized incidence of stroke with medical therapy was 1.09% (95% CI, 0.88%-1.36%) and with device closure was 0.47% (95% CI, 0.35%-0.65%) (adjusted hazard ratio [HR], 0.41 [95% CI, 0.28-0.60]). The subgroup analyses showed statistically significant interaction effects. Patients with low vs high RoPE Score had HRs of 0.61 (95% CI, 0.37-1.00) and 0.21 (95% CI, 0.11-0.42), respectively (P for interaction = .02). Patients classified as unlikely, possible, and probable using the PASCAL Classification System had HRs of 1.14 (95% CI, 0.53-2.46), 0.38 (95% CI, 0.22-0.65), and 0.10 (95% CI, 0.03-0.35), respectively (P for interaction = .003). The 2-year absolute risk reduction was -0.7% (95% CI, -4.0% to 2.6%), 2.1% (95% CI, 0.6%-3.6%), and 2.1% (95% CI, 0.9%-3.4%) in the unlikely, possible, and probable PASCAL categories, respectively. Device-associated adverse events were generally higher among patients classified as unlikely; the absolute risk increases in atrial fibrillation beyond day 45 after randomization with a device were 4.41% (95% CI, 1.02% to 7.80%), 1.53% (95% CI, 0.33% to 2.72%), and 0.65% (95% CI, -0.41% to 1.71%) in the unlikely, possible, and probable PASCAL categories, respectively. Conclusions and Relevance: Among patients aged 18 to 60 years with PFO-associated stroke, risk reduction for recurrent stroke with device closure varied across groups classified by their probabilities that the stroke was causally related to the PFO. Application of this classification system has the potential to guide individualized decision-making.

Initial experience with the fourth generation MitraClip™: Outcomes, procedural aspects, and considerations for device selection.

OBJECTIVES: We present our initial experience with the fourth-generation MitraClip™ (G4) system and propose preliminary criteria for device selection. BACKGROUND: The MitraClip™ G4 system recently underwent a "controlled release" for transcatheter edge-to-edge mitral valve repair. The four new devices include technical improvements such as controlled gripper actuation (independent leaflet capture) and continuous left atrial pressure monitoring. To date, a patient-specific device selection algorithm, and the technology's impact on procedural times and success, have not been described. METHODS: We present an initial multi-center experience and short-term outcomes with the new system, suggest procedural and imaging considerations, and propose initial guidance for device selection. RESULTS: Sixty-one procedures performed by three operators at two centers between November 2019 and May 2020 were analyzed. At 30-day follow-up, there were three deaths (4.9%), four neurological events (6.6%), and seven re-hospitalizations (11.5%). Fifty-nine patients achieved device and procedural success (96.7%), and there was one device-related technical issue (1.6%). Compared to the same operators utilizing the third generation MitraClip™, the G4 system resulted in a significant reduction in the median number of clips used per patient (1 IQR 1-2 vs. 2 IQR 1-3, p = .023) and a trend toward shorter device times. CONCLUSION: Based on our initial experience, we found that the MitraClip™ G4 system is associated with high procedural success and fewer devices needed per procedure. The expanded device options may allow a more targeted approach to the myriad of pathologic presentations of mitral regurgitation. This early experience should provide a foundational opportunity for further refinement.

Trends and Impact of the Use of Mechanical Circulatory Support for Cardiogenic Shock Secondary to Takotsubo Cardiomyopathy.

Data on the trend and impact of mechanical circulatory support (MCS) in patients with Takotsubo cardiomyopathy (TC) are scarce. We evaluated the incidence and outcomes of cardiogenic shock (CS) in TC patients and the trend in use of MCS over time. The National Inpatient Sample from 2005 to 2014 was used to identify patients admitted with TC and those receiving MCS. Multivariate logistic regression was performed to identify predictors of mortality. The Cochran-Armitage test was used for the trend analysis across the years. Admissions for TC showed a linear increase for the study period. From 2005 to 2014 the proportion of TC managed with MCS remained stable, with some yearly fluctuations. Crude in-hospital mortality rate was 2.5% in the patients admitted with TC but was significantly higher in those with CS (15.81% vs 1.68%, p < 0.001). There was no difference in mortality in TC patients with CS, both with and without the use of MCS. However, patients managed with MCS were more likely to be discharged to a skilled nursing facility (31% vs 25.55, p = 0.015) compared with TC patients with CS who were medically managed. The cost of care for patients with TC and CS, managed with MCS was significantly higher than those managed medically ($171K vs $128K, p <0.001). In patients managed with MCS, only sepsis was associated with a higher likelihood of death using multivariate analysis (Odds Ratio 2.538, Confidence Interval 1.245 to 5.172; p = 0.011). In conclusion, the incidence of TC has increased over the years, but the proportion of patients requiring MCS has declined. Crude mortality rate for TC was 2.5%, but was 15.8% in the TC patients with CS. The use of MCS did not lead to improved mortality but was associated with higher cost and increased likelihood of skilled nursing facility discharge.

Risk of Paradoxical Embolism (RoPE)-Estimated Attributable Fraction Correlates With the Benefit of Patent Foramen Ovale Closure: An Analysis of 3 Trials.

BACKGROUND AND PURPOSE: In patients with cryptogenic stroke and patent foramen ovale (PFO), the Risk of Paradoxical Embolism (RoPE) Score has been proposed as a method to estimate a patient-specific "PFO-attributable fraction"-the probability that a documented PFO is causally-related to the stroke, rather than an incidental finding. The objective of this research is to examine the relationship between this RoPE-estimated PFO-attributable fraction and the effect of closure in 3 randomized trials. METHODS: We pooled data from the CLOSURE-I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent Foramen Ovale), RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment), and PC (Clinical Trial Comparing Percutaneous Closure of Patent Foramen Ovale [PFO] Using the Amplatzer PFO Occluder With Medical Treatment in Patients With Cryptogenic Embolism) trials. We examine the treatment effect of closure in high RoPE score (≥7) versus low RoPE score (<7) patients. We also estimated the relative risk reduction associated with PFO closure across each level of the RoPE score using Cox proportional hazard analysis. We estimated a patient-specific attributable fraction using a PC trial-compatible (9-point) RoPE equation (omitting the neuroradiology variable), as well as a 2-trial analysis using the original (10-point) RoPE equation. We examined the Pearson correlation between the estimated attributable fraction and the relative risk reduction across RoPE strata. RESULTS: In the low RoPE score group (<7, n=912), the rate of recurrent strokes per 100 person-years was 1.37 in the device arm versus 1.68 in the medical arm (hazard ratio, 0.82 [0.42-1.59] P=0.56) compared with 0.30 versus 1.03 (hazard ratio, 0.31 [0.11-0.85] P=0.02) in the high RoPE score group (≥7, n=1221); treatment-by-RoPE score group interaction, P=0.12. The RoPE score estimated attributable fraction anticipated the relative risk reduction across all levels of the RoPE score, in both the 3-trial (r=0.95, P<0.001) and 2-trial (r=0.92, P<0.001) analyses. CONCLUSIONS: The RoPE score estimated attributable fraction is highly correlated to the relative risk reduction of device versus medical therapy. This observation suggests the RoPE score identifies patients with cryptogenic stroke who are likely to have a PFO that is pathogenic rather than incidental.

One-Year Outcomes of Mitral Valve-in-Valve Using the SAPIEN 3 Transcatheter Heart Valve.

Importance: Bioprosthetic mitral valves are implanted with increasing frequency but inevitably degenerate, leading to heart failure. Reoperation is associated with high morbidity and mortality. Transcatheter mitral valve-in-valve (MViV) using balloon-expandable transcatheter valves has emerged as an alternative for high-surgical risk patients. Objective: To assess contemporary outcomes of SAPIEN 3 (Edwards Lifesciences) MViV replacement. Design, Setting, and Participants: In this registry-based prospective cohort study of SAPIEN 3 MViV, patients entered in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry from June 2015 to July 2019 were analyzed. US Centers for Medicare and Medicaid linkage ensured comprehensive collection of death and stroke data. Exposures: Mitral valve-in-valve for degenerated bioprosthetic mitral valves. Main Outcomes and Measures: The primary efficacy end point was 1-year mortality. The primary safety end point was procedural technical success as defined by the Mitral Valve Academic Research Consortium criteria. Secondary end points included 30-day mortality, New York Heart Association-defined heart failure, and mitral valve performance. Results: A total of 1529 patients (mean [SD] age, 73.3 [11.84] years; 904 women [59.1%]) underwent transseptal or transapical MViV implant at 295 hospitals between June 2015 and July 2019. The mean (SD) Society of Thoracic Surgeons predicted risk of mortality was 11.1% (8.7%). Procedural technical success was achieved for 1480 of 1529 patients (96.8%). All-cause mortality was 5.4% at 30 days and 16.7% at 1 year. Transseptal access was associated with lower 1-year all-cause mortality than transapical access (15.8% vs 21.7%; P = .03). Transcatheter MViV led to early, sustained, and clinically meaningful improvements in heart failure (class III/IV New York Heart Association heart failure of 87.1% at baseline vs 9.7% at 1 year). The mean (SD) mitral valve gradient at 1 year was 7 (2.89) mm Hg. Conclusions and Relevance: Transcatheter MViV using the SAPIEN 3 transcatheter heart valve is associated with high technical success, low 30-day and 1-year mortality, significant improvement of heart failure symptoms, and sustained valve performance. Transseptal MViV should be considered an option for most patients with failed surgical bioprosthetic valves and favorable anatomy.

Outcomes of Patients Undergoing Transcatheter Aortic Valve Implantation With Incidentally Discovered Masses on Computed Tomography.

Routine preprocedural chest and abdomen computed tomography is done prior to transcatheter aortic valve implantation (TAVI), which, in turn, have led to the discovery of radiographic potentially malignant incidental masses (pMIM). It is largely unknown whether pMIM impact the outcomes of patients undergoing TAVI. In this retrospective cohort study from a single center, 1,081 patients underwent TAVI from 2012 to 2016, who had available computed tomographies, survived the index hospitalization, and also had 1 year follow-up data for review. Machine learning (backward propagation neural network)-augmented multivariable regression for mortality by pMIM was conducted. In this cohort of 1,081 patients, the mean age was 79.1 (± 9.0), 48.8% were females, 16.8% had a history of prior malignancy, and 21.1% had pMIM. One-year mortality for the entire cohort was 12.6%. The most common prior malignancies were prostate, breast, and lymphoma and the most common pMIM were present in the lung, kidneys, and thyroid. In a fully adjusted regression analysis, neither prior malignancy nor pMIM increased mortality odds. However, having both was associated with a higher 1-year mortality (odds ratio 4.02, 95% confidence interval 1.50 to 10.73, p = 0.006). In conclusion, presence of pMIM alone was not associated with an increased 1-year mortality among patients undergoing TAVI. However, the presence of pMIM and a history of prior malignancy was associated with a significant increase in 1-year mortality.

Rates, predictors, and outcomes of early readmissions after tricuspid valve surgery.

BACKGROUND: The data on readmissions following tricuspid valve repair/replacement (TVR) are scarce. We examined rates, predictors, causes, and outcomes of readmissions after TVR, using the National Readmission Database. METHODS: The International Classification of Diseases-9th version was used to identify the patients who underwent isolated TVR or concomitant aortic, mitral, and coronary bypass surgeries. Rates, causes, and outcomes were assessed using the analysis of variance and the χ2 test, and predictors of readmissions were evaluated using multivariate analysis. RESULTS: A total of 8254 patients who underwent TVR during 2013 to 2014 were included, of whom 1994 (24.16%) were isolated, and 6260 (75.84%) were performed concomitantly with other heart valve or coronary bypass surgery. A total of 1720 (20.84%) patients were readmitted within 30 days. The readmission rates were 448 (22.46%) after isolated TVR and similar after concomitant TVR (TVR + aortic valve replacement, TVR + mitral valve repair, TVR + coronary artery bypass graft, and TVR + multiple) (P = .194); whereas 1305 (20.11%) and 414 (23.45%) were after tricuspid valve repair and replacement (P = .080), respectively. The independent predictors of readmission were acute kidney injury during index visit and Charlson comorbidity index of more than 2. Mean time to readmission and median length of stay during readmission were 13.02 (±7.93) and 5 (interquartile range: 3-9) days, respectively. Total mortality during rehospitalization was 105 (6.1%), a very high (26.86%) number of patients were discharged to skilled facilities after readmission. CONCLUSIONS: One out of five patients were readmitted within 30 days after the TVR, associated with 6.1% mortality during rehospitalization, and very high need for skilled facility placement.

Validation of scoring system predicting permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with severe aortic stenosis. Despite newer generation valves, atrioventricular (AV) conduction disturbance is a common complication, necessitating permanent pacemaker (PPM) implantation in about 10% of patients. Hence, it is imperative to improve periprocedural risk stratification to predict PPM implantation after TAVR. The objective of this study was to externally validate a novel risk-stratification model derived from the National Inpatient Sample (NIS) database that predicts risk of PPM from TAVR. METHODS: Components of the score included pre-TAVR left and right bundle branch block, sinus bradycardia, second-degree AV block, and transfemoral approach. The scoring system was applied to 917 patients undergoing TAVR at our institution from November 2011 to February 2017. We assessed its predictive accuracy by looking at two components: discrimination using the C-statistic and calibration using the Hosmer-Lemeshow goodness of fit test. RESULTS: Ninety patients (9.8%) required PPM. The scoring system showed good discrimination with C-statistic score of 0.6743 (95% CI: 0.618-0.729). Higher scores suggested increased PPM risk, that is, 7.3% with score ⩽3, 19.23% with score 4-6, and 37.50% with score ≥7. Patients requiring PPM were older (81.4 versus 78.7 years, P = .002). Length of stay and in-hospital mortality was significantly higher in PPM group. CONCLUSIONS: The NIS database derived PPM risk prediction model was successfully validated in our database with acceptable discriminative and gradation capacity. It is a simple but valuable tool for patient counseling pre-TAVR and in identifying high-risk patients.

An Unusual Cause of Hypoxia: Ventricular Septal Defect, Pulmonary Artery Atresia, and Major Aortopulmonary Collaterals Diagnosed in the Adult Cardiac Catheterization Lab.

The association of pulmonary atresia, ventricular septal defect (VSD) and major aortopulmonary collaterals (MAPCA) is an extreme form of tetralogy of Fallot (TOF). It carries a high mortality risk if not intervened on during infancy with only 20% of unoperated patients surviving into adulthood. We present the case of a 40-year-old man who presented for evaluation prior to retinal surgery and was found to have hypoxia and a loud murmur. Cardiac catheterization was performed in the general catheterization laboratory, demonstrating a membranous VSD, pulmonary atresia, and MAPCA. We highlight the challenges and limitations that an adult interventional cardiologist may have when encountering these patients.

New-onset left bundle branch block after transcatheter aortic valve replacement is associated with adverse long-term clinical outcomes in intermediate-risk patients: an analysis from the PARTNER II trial.

AIMS: Transcatheter aortic valve replacement (TAVR) is now an established therapy for intermediate-risk surgical candidates with symptomatic, severe aortic stenosis. The clinical impact of new-onset left bundle branch block (LBBB) after TAVR remains controversial and has not been studied in intermediate-risk patients. We therefore sought to analyse outcomes associated with new LBBB in a large cohort of intermediate-risk patients treated with TAVR. METHODS AND RESULTS: A total of 2043 patients underwent TAVR in the PARTNER II trial and S3 intermediate-risk registry and survived to hospital discharge. Patients were excluded from the current analysis due to baseline conduction disturbances, pre-existing permanent pacemaker (PPM), and new PPM during the index hospitalization. Clinical outcomes at 2 years were compared between patients with and without persistent, new-onset LBBB at hospital discharge, and multivariable analysis was performed to identify predictors of mortality. Among 1179 intermediate-risk patients, new-onset LBBB at discharge occurred in 179 patients (15.2%). Patients with new LBBB were similar to those without except for more frequent diabetes and more frequent treatment with SAPIEN 3 vs. SAPIEN XT. At 2 years, new LBBB was associated with increased rates of all-cause mortality (19.3% vs. 10.8%, P = 0.002), cardiovascular mortality (16.2% vs. 6.5%, P < 0.001), rehospitalization, and new PPM implantation. By multivariable analysis, new LBBB remained an independent predictor of 2-year all-cause [hazard ratio (HR) 1.98, 95% confidence interval (95% CI) 1.33, 2.96; P < 0.001] and cardiovascular (HR 2.66 95% CI 1.67, 4.24; P < 0.001) mortality. New LBBB was also associated with worse left ventricular systolic function at 1 and 2-year follow-up. CONCLUSIONS: In a large cohort of intermediate-risk patients from the PARTNER II trial and registry, persistent, new-onset LBBB occurred in 15.2% of patients without baseline conduction disturbances or pacemaker. New LBBB was associated with adverse clinical outcomes at 2 years, including all-cause and cardiovascular mortality, rehospitalization, new pacemaker implantation, and worsened left ventricular systolic function. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov #NCT01314313 and NCT03222128.

Anticoagulation After Surgical or Transcatheter Bioprosthetic Aortic Valve Replacement.

BACKGROUND: There is paucity of evidence on the impact of anticoagulation (AC) after bioprosthetic aortic valve replacement (AVR) on valve hemodynamics and clinical outcomes. OBJECTIVES: The study aimed to assess the impact of AC after bioprosthetic AVR on valve hemodynamics and clinical outcomes. METHODS: Data on antiplatelet and antithrombotic therapy were collected. Echocardiograms were performed at 30 days and 1 year post-AVR. Linear regression model and propensity-score adjusted cox proportional model were used to assess the impact of AC on valve hemodynamics and clinical outcomes, respectively. RESULTS: A total of 4,832 patients undergoing bioprosthetic AVR (transcatheter aortic valve replacement [TAVR], n = 3,889 and surgical AVR [SAVR], n = 943) in the pooled cohort of PARTNER2 (Placement of Aortic Transcatheter Valves) randomized trials and nonrandomized registries were studied. Following adjustment for valve size, annular diameter, atrial fibrillation, and ejection fraction at the time of assessment of hemodynamics, there was no significant difference in aortic valve mean gradients or aortic valve areas between patients discharged on AC vs. those not discharged on AC, for either TAVR or SAVR cohorts. A significantly greater proportion of patients not discharged on AC had an increase in mean gradient >10 mm Hg from 30 days to 1 year, compared with those discharged on AC (2.3% vs. 1.1%, p = 0.03). There was no independent association between AC after TAVR and adverse outcomes (death, p = 0.15; rehospitalization, p = 0.16), whereas AC after SAVR was associated with significantly fewer strokes (hazard ratio [HR]: 0.17; 95% confidence interval [CI]: 0.05-0.60; p = 0.006). CONCLUSIONS: In the short term, early AC after bioprosthetic AVR did not result in adverse clinical events, did not significantly affect aortic valve hemodynamics (aortic valve gradients or area), and was associated with decreased rates of stroke after SAVR (but not after TAVR). Whether early AC after bioprosthetic AVR has impact on long-term outcomes remains to be determined. (Placement of AoRTic TraNscathetER Valves [PARTNERII A]; NCT01314313).

Preload Sensitivity with TORVAD Counterpulse Support Prevents Suction and Overpumping.

PURPOSE: This study compares preload sensitivity of continuous flow (CF) VAD support to counterpulsation using the Windmill toroidal VAD (TORVAD). The TORVAD is a two-piston rotary pump that ejects 30 mL in early diastole, which increases cardiac output while preserving aortic valve flow. METHODS: Preload sensitivity was compared for CF vs. TORVAD counterpulse support using two lumped parameter models of the cardiovascular system: (1) an open-loop model of the systemic circulation was used to obtain ventricular function curves by isolating the systemic circulation and prescribing preload and afterload boundary conditions, and (2) a closed-loop model was used to test the physiological response to changes in pulmonary vascular resistance, systemic vascular resistance, heart rate, inotropic state, and blood volume. In the open-loop model, ventricular function curves (cardiac output vs left ventricular preload) are used to assess preload sensitivity. In the closed-loop model, left ventricular end systolic volume is used to assess the risk of left ventricular suction. RESULTS: At low preloads of 5 mmHg, CF support overpumps the circulation compared to TORVAD counterpulse support (cardiac output of 3.3 L/min for the healthy heart, 4.7 with CF support, and 3.5 with TORVAD counterpulse support) and has much less sensitivity than counterpulse support (0.342 L/min/mmHg for the healthy heart, 0.092 with CF support, and 0.306 with TORVAD counterpulse support). In the closed-loop model, when PVR is increased beyond 0.035 mmHg s/mL, CF support overpumps the circulation and causes ventricular suction events, but TORVAD counterpulse support maintains sufficient ventricular volume and does not cause suction. CONCLUSIONS: Counterpulse support with the TORVAD preserves aortic valve flow and provides physiological sensitivity across all preload conditions. This should prevent overpumping and minimize the risk of suction.

Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits.

Peripheral vascular disease is a widespread clinical problem that affects millions of patients worldwide. A major consequence of peripheral vascular disease is the development of ischemia. In severe cases, patients can develop critical limb ischemia in which they experience constant pain and an increased risk of limb amputation. Current therapies for peripheral ischemia include bypass surgery or percutaneous interventions such as angioplasty with stenting or atherectomy to restore blood flow. However, these treatments often fail to the continued progression of vascular disease or restenosis or are contraindicated due to the overall poor health of the patient. A promising potential approach to treat peripheral ischemia involves the induction of therapeutic neovascularization to allow the patient to develop collateral vasculature. This newly formed network alleviates peripheral ischemia by restoring perfusion to the affected area. The most frequently employed preclinical model for peripheral ischemia utilizes the creation of hind limb ischemia in healthy rabbits through femoral artery ligation. In the past, however, there has been a strong disconnect between the success of preclinical studies and the failure of clinical trials regarding treatments for peripheral ischemia. Healthy animals typically have robust vascular regeneration in response to surgically induced ischemia, in contrast to the reduced vascularity and regeneration in patients with chronic peripheral ischemia. Here, we describe an optimized animal model for peripheral ischemia in rabbits that includes hyperlipidemia and diabetes. This model has reduced collateral formation and blood pressure recovery in comparison to a model with a higher cholesterol diet. Thus, the model may provide better correlation with human patients with compromised angiogenesis from the common co-morbidities that accompany peripheral vascular disease.