Cost Utility of Transcatheter Aortic Valve Replacement: Sapien 3 Versus CoreValve Evolut R.

Transcatheter aortic valve replacement (TAVR) has become the preferred treatment for severe aortic stenosis. Previous studies compare clinical outcomes of leading TAVR valves, but there is no evidence of cost-utility comparison, leaving a clinical information gap when selecting valves. Here we share a cost-utility analysis comparing the Sapien 3 (S3) (Edwards Lifesciences, Irvine, CA) and CoreValve Evolut R (ER) (Medtronic, Dublin, IR) across five clinical endpoints. Utility scores from patient surveys and clinical outcomes from the literature were used to estimate quality-adjusted life years (QALYs) associated with successful procedure and postoperative complications for S3 and ER. A decision tree was constructed with rollback analysis to highlight the more cost-effective strategy. An incremental cost-utility ratio (ICUR) analysis was performed with a willingness to pay at $50,000. Deterministic and probabilistic sensitivity analyses were performed to validate robustness of results and account for uncertainty. S3 was found to be more costly ($68,377 vs. $66,072), but more effective (1.87 vs . 1.66) compared with ER. An ICUR of 11,288.12 favored S3, making it the more cost-effective option with a moderate confidence of 73.68% in Monte Carlo analysis. Cost-utility analysis can be used to aid in healthcare economics decision-making when selecting between comparable technologies used for TAVR procedures.

Pre-procedural serum albumin concentration is associated with length of stay, discharge destination, and 90-day mortality in patients after transcatheter aortic valve replacement.

Background: As visceral protein expression may influence outcomes in patients with cardiovascular disease, we investigated whether pre-procedural albumin concentration is associated with length of stay (LOS) and 90-day mortality after transcatheter aortic valve repair (TAVR). Methods: We retrospectively analyzed data from TAVR patients at our institution between January 2013 and December 2017. For all patients, baseline albumin concentration was assessed between one and four weeks before the procedure. To investigate the association between albumin concentration and outcomes, we performed regression analyses, controlling for Society of Thoracic Surgeons, New York Heart Association classification, and Kansas City Cardiomyopathy Questionnaire 12 scores. Results: Three hundred eighty patients were included in the analyses. Cox-proportional hazards regression showed that patients with albumin concentrations <3.5 g/dL were 80% more likely to have prolonged ICU LOS (HR 1.79; 95%CI 1.04-2.57, P = 0.03) and 70% more likely to have prolonged hospital LOS (HR 1.68; 95%CI 1.01-2.46, P = 0.04) compared to patients with albumin concentrations >3.5 g/dL. Logistic regression showed that patients with albumin concentrations <3.5 g/dL were four times more likely to not survive to 90 days (OR 3.94; 1.13-12.63, P = 0.03) after their TAVR compared to patients with albumin concentrations >3.5 g/dL. Conclusion: Our data suggest that patients with pre-procedural albumin concentrations <3.5 g/dL are at an increased risk of adverse outcomes after TAVR compared to patients with albumin concentrations ≥3.5 g/dL. Prospective studies are needed to determine whether risk stratification based on pre-procedural albumin can improve outcomes and whether targeted interventions can improve pre-procedural albumin concentrations in potential TAVR candidates.

Left ventricular stroke volume index following transcatheter aortic valve replacement is an early predictor of 1-year survival.

BACKGROUND: Adverse cardiac events are common following transcatheter aortic valve replacement (TAVR). Our aim was to investigate the low left ventricular stroke volume index (LVSVI) 30 days after TAVR as an early echocardiographic marker of survival. HYPOTHESIS: Steady-state (30-day) LVSVI after TAVR is associated with 1-year mortality. METHODS: A single-center retrospective analysis of all patients undergoing TAVR from 2017 to 2019. Baseline and 30-day post-TAVR echocardiographic LVSVI were calculated. Patients were stratified by pre-TAVR transaortic gradient, surgical risk, and change in transvalvular flow following TAVR. RESULTS: This analysis focuses on 238 patients treated with TAVR. The 1-year mortality rate was 9% and 124 (52%) patients had normal flow post-TAVR. Of those with pre-TAVR low flow, 67% of patients did not normalize LVSVI at 30 days. The 30-day normal flow was associated with lower 1-year mortality when compared to low flow (4% vs. 14%, p = .007). This association remained significant after adjusting for known predictors of risk (adjusted odds ratio [OR] of 3.45, 95% confidence interval: 1.02-11.63 [per 1 ml/m2 decrease], p = .046). Normalized transvalvular flow following TAVR was associated with reduced mortality (8%) when compared to those with persistent (15%) or new-onset low flow (12%) (p = .01). CONCLUSIONS: LVSVI at 30 days following TAVR is an early echocardiographic predictor of 1-year mortality and identifies patients with worse intermediate outcomes. More work is needed to understand if this short-term imaging marker might represent a novel therapeutic target.

Association of preprocedural ultrashort-term heart rate variability with clinical outcomes after transcatheter aortic valve replacement: A nested, case-control, pilot study.

Background: Because heart rate variability (HRV) has been linked to important clinical outcomes in various cardiovascular disease states, we investigated whether preprocedural ultrashort-term HRV (UST-HRV) differs between 1-year survivors and nonsurvivors after transcatheter aortic valve replacement (TAVR). Methods: In our single-center, retrospective, nested pilot study, we analyzed data from patients with severe aortic stenosis undergoing TAVR. All patients had preprocedural UST-HRV measured before the administration of any medications or any intervention. To investigate whether preprocedural HRV is associated with 1-year survival, we performed a logistic regression analysis controlling for Kansas City Cardiomyopathy Questionnaire 12 score. Results: In our parent cohort of 100 patients, 42 patients (28 survivors and 14 nonsurvivors) were included for analysis. Root mean square of successive differences (RMSSD) and standard deviation of NN intervals (SDNN) were lower in patients who survived to 1-year post TAVR compared to nonsurvivors [10 (IQR 8-23) vs 23 (IQR 17-33), P = 0.04 and 10 (IQR 7-16) vs 17 (IQR 11-40), P = 0.03, respectively]. Logistic regression demonstrated a trend in the association of preprocedure RMSSD with 1-year mortality and a 5% higher risk of 1-year mortality with each unit increment in UST-HRV using SDNN (OR 1.05; 95%CI 1.01-1.09, P = 0.02). Conclusion: Our data suggest an inverse relationship between preprocedural UST-HRV and 1-year survival post-TAVR. This finding highlights the potential complexity of HRV regulation in chronic vs acute illness. Prospective studies are needed to validate our findings and to determine whether UST-HRV can be used for risk stratification in patients with severe aortic stenosis.

Transcarotid transcatheter aortic valve replacement with cerebral embolic protection.

There remains concern about the risk of stroke with transcarotid transcatheter aortic valve replacement (TAVR). We describe the use of the Sentinel cerebral protection device with transcarotid TAVR in a patient at high risk for embolic complications. Deployment of the Sentinel filter in the innominate artery accommodated the insertion of the TAVR device through the bovine aortic arch via the contralateral carotid artery. By adapting the "flip-n-flex" technique from our previous transaxillary TAVR experience, we performed left transcarotid TAVR with the Sentinel device in an ergonomic manner and achieved coaxial placement of the transcatheter valve. Inspection of the Sentinel filter after the case revealed captured embolic debris.

Transcarotid Transcatheter Aortic Valve Replacement With Simple "Flip-n-Flex" Technique.

Transcarotid transcatheter aortic valve replacement (TAVR) is increasingly accepted as a safe and efficacious alternative when transfemoral access is contraindicated. Technical and anatomic considerations unique to transcarotid access warrant several adaptations to the routine TAVR procedure. This report describes an approach to overcome these challenges and improve efficiency, including adoption of the "flip-n-flex" technique originally developed for right transaxillary TAVR. This technique has been used at Tufts Medical Center (Boston, MA) since 2019 in both left and right transcarotid TAVR approaches with success to ensure coaxial alignment of the transcatheter heart valve to the aortic root.

Comorbidity Burden and Adverse Outcomes After Transcatheter Aortic Valve Replacement.

Background Transcatheter aortic valve replacement (TAVR) has become the preferred treatment for symptomatic patients with aortic stenosis and elevated procedural risk. Many deaths following TAVR are because of noncardiac causes and comorbid disease burden may be a major determinant of postprocedure outcomes. The prevalence of comorbid conditions and associations with outcomes after TAVR has not been studied. Methods and Results This was a retrospective single-center study of patients treated with TAVR from January 2015 to October 2018. The association between 21 chronic conditions and short- and medium-term outcomes was assessed. A total of 341 patients underwent TAVR and had 1-year follow-up. The mean age was 81.4 (SD 8.0) years with a mean Society of Thoracic Surgeons predicted risk of mortality score of 6.7% (SD 4.8). Two hundred twenty (65%) patients had ≥4 chronic conditions present at the time of TAVR. There was modest correlation between Society of Thoracic Surgeons predicted risk of mortality and comorbid disease burden (r=0.32, P<0.001). After adjusting for Society of Thoracic Surgeons predicted risk of mortality, age, and vascular access, each additional comorbid condition was associated with increased rates of 30-day rehospitalizations (odds ratio, 1.21; 95% CI, 1.02-1.44), a composite of 30-day rehospitalization and 30-day mortality (odds ratio, 1.20; 95% CI, 1.02-1.42), and 1-year mortality (odds ratio, 1.29; 95% CI, 1.05-1.59). Conclusions Comorbid disease burden is associated with worse clinical outcomes in high-risk patients treated with TAVR. The risks associated with comorbid disease burden are not adequately captured by standard risk assessment. A systematic assessment of comorbid conditions may improve risk stratification efforts.

Tissue Doppler Imaging (E/e') and Pulmonary Capillary Wedge Pressure in Patients With Severe Aortic Stenosis.

OBJECTIVE: Although American and European consensus statements advocate using the ratio of the transmitral E velocity and tissue Doppler early diastolic mitral annular velocity (E/e') in the assessment of left-sided heart filling pressures, recent reports have questioned the reliability of this ratio to predict left atrial pressures in a variety of disease states. The authors hypothesized that there is a clinically significant correlation between E/e' and pulmonary capillary wedge pressure (PCWP) in patients with severe aortic stenosis. DESIGN: Retrospective cohort study. PARTICIPANTS: The study comprised 733 consecutive patients with severe aortic stenosis who underwent transcatheter aortic valve replacement for severe aortic stenosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PCWP and E/e'ave (average of the lateral and medial annulus tissue Doppler velocities) were measured with a pulmonary artery catheter and transthoracic echocardiography during preprocedural evaluation. Patients were grouped by left ventricular ejection fraction (LVEF) ≥50% and LVEF <50%. Spearman rank correlation, analysis of variance, and t and chi-square tests were used to analyze the data. Seventy-nine patients met the inclusion criteria. There was no significant correlation between E/e'ave and PCWP (n = 79, Spearman r = 0.096; p = 0.3994). This correlation did not improve when ventricular function was considered (LVEF <50%: n = 11, Spearman r = -0.097; p = 0.776 and LVEF ≥50%: n = 68, Spearman r = 0.116; p = 0.345). There was no statistically significant difference in mean PCWP between each range of E/e'ave. CONCLUSION: A clinically relevant relationship between E/e' and PCWP was not observed in patients with severe aortic stenosis.

Skeletal Muscle Characteristics May Inform Preprocedural Risk Stratification in Transcatheter Aortic Valve Replacement Patients.

OBJECTIVES: Low psoas muscle mass previously has been associated with mortality after transcatheter aortic valve replacement (TAVR). Evidence from other clinical disciplines suggests that psoas density (PD) may be a better predictor than psoas muscle cross-sectional area indexed to body surface area (PI). The authors hypothesized that PD would be more strongly correlated with patient discharge disposition and survival after TAVR than PI. DESIGN: The authors performed a single-center, retrospective study of TAVR patients from 2013 to 2016. PI and PD were assessed at the third lumbar spine level using computed tomography imaging. Propensity-score matching was used to investigate the association of PI and PD with discharge disposition and mortality. SETTING: Tertiary university hospital PARTICIPANTS: Cohort of 245 TAVR patients. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: A total of 245 patients met inclusion criteria. Following propensity score matching, patients with PI <4 cm2/m2 and PD <25 Hounsfield units (HU) were less likely to survive and to be discharged home compared with patients with PI ≥4 cm2/m2 or PD >25 HU. After repeating the propensity score matching with PI as a covariable, PD remained associated with mortality (90 days: odds ratio [OR] 4.59; 95% confidence interval [CI] 2.96-10.31, p < 0.001, 1 year: OR 6.14; 95% CI 3.45-28.57, p = 0.01, 3 years: OR 4.55; 95% CI 2.41-40.00, p = 0.03). CONCLUSIONS: PD may be more relevant than PI in risk stratification for TAVR patients.

Can Clinical Predictive Models Identify Patients Who Should Not Receive TAVR? A Systematic Review.

BACKGROUND: One third of high- and prohibitive-risk TAVR patients remain severely symptomatic or die 1 year after treatment. There is interest in identifying individuals for whom this procedure is futile and should not be offered. METHODS: We performed a systematic review of the highest reported stratum of risk in TAVR clinical predictive models (CPMs). We explore whether currently available predictive models can identify patients for whom TAVR is futile, based on a quantitative futility definition and the observed and predicted outcomes for patients in the highest stratum of risk. RESULTS: 17 TAVR CPMs representing 69,191 treated patients were published from 2013 to 2018. When reported, the median number of patients in the highest stratum of risk was 569 (range 1 to 1759). Observed mortality for this risk stratum ranged from 9% at 30 days to 59% at 1 year after TAVR. Statistical confidence in these observed event rates was low. The highest predicted event rates ranged from 11.0% for in-hospital mortality to 75.1% for the composite of mortality or high symptom burden 1 year after TAVR. CONCLUSION: No high-risk TAVR group in currently available TAVR CPMs had an appropriate event rate and adequate statistical power to meet a quantitative definition of futility.

Safety and efficacy of transaxillary transcatheter aortic valve replacement using a current-generation balloon-expandable valve.

BACKGROUND: Transaxillary access (TAx) has shown promise as an excellent alternative TAVR option, but data on the Edwards SAPIEN 3 in TAx-TAVR is limited. We sought to study the safety and efficacy of TAx-TAVR using this current-generation balloon-expandable valve. METHODS: A retrospective study of our first 24 TAx and 20 transthoracic (TT) TAVR patients treated with the SAPIEN 3 valve was performed, and the patients' preoperative characteristics, procedural outcomes, and clinical outcomes were compared to our first 100 transfemoral (TF) patients using the SAPIEN 3 device. RESULTS: There were no statistical differences observed for outcomes between the TAx and TF groups, despite the TAx patients having more comorbidities (STS-PROM 11.3 ± 7.6 versus 7.3 ± 5.2, p = 0.042). In addition, no significant difference was found in the fluoroscopy time and contrast amount between the two groups. The patients' baseline characteristics were similar between the TAx and TT groups. Their procedural and clinical outcomes were comparable, but there was a trend towards lower incidence of acute kidney injury (13.0% versus 23.5%), new-onset atrial fibrillation (5.6% versus 33.3%), shorter median length of stay postoperatively (4 versus 6 days), fewer discharges to rehabilitation (16.7% versus 35.0%), and a lower rate of readmission within 30-days (8.3% versus 35.0%), all favoring TAx access. CONCLUSIONS: TAx-TAVR with the SAPIEN 3 valve is a safe alternative to TF access. It offers advantages of improved recovery over TT access, and appears to be a superior alternative-access option for TAVR. TAx access could be preferred when TF access is not feasible.

Right Transaxillary Transcatheter Aortic Valve Replacement Using the "Flip-n-Flex" Technique.

BACKGROUND: Right transaxillary transcatheter aortic valve replacement (TAx-TAVR) is rarely performed due to challenging vascular tortuosity and unfavorable implantation angles. We explored this procedure using the newer-generation balloon-expandable SAPIEN 3 (Edwards Lifesciences, Irvine, CA) valve and our novel "flip-n-flex" technique. The safety and effectiveness of the procedure and the learning curve of our early experiences were investigated. METHODS: The first 10 consecutive patients undergoing right TAx-TAVR performed at our center from June 2016 to May 2018 were included in the study. Patients' preoperative characteristics, procedural outcomes, and clinical outcomes were studied. Intraoperative fluoroscopy times were also reviewed to analyze the procedural learning curve. RESULTS: The 10 patients were a mean age of 81.8 ± 8.7 years, and 5 patients (50%) were women. Mean Society of Thoracic Surgeons Predicted Risk of Mortality was 12.0% ± 9.5%. Procedural success was achieved in all cases without vascular complications. Paravalvular leak was absent or mild in all patients. Two patients (20%) required permanent pacemaker implantation. The median postoperative length of stay was 4 days (range, 2-13 days). The 30-day mortality was 0%. Mean transvalvular gradient improved from 38.4 ± 12.6 mm Hg to 9 ± 4.4 mm Hg postoperatively. New York Heart Association Functional Classification improved in all patients. The fluoroscopy time showed marked reduction from 44.1 ± 8.2 minutes to 17.4 ± 2.9 minutes with the use of the flip-n-flex technique. CONCLUSIONS: Our early experience of right TAx-TAVR with the SAPIEN 3 valve demonstrated satisfactory outcomes and a quick learning as facilitated by the flip-n-flex technique. This could be a beneficial TAVR approach to suitable patients.

Guideline-Based Referral for Septal Reduction Therapy in Obstructive Hypertrophic Cardiomyopathy Is Associated With Excellent Clinical Outcomes.

BACKGROUND: The outcome of medically refractory patients with obstructive hypertrophic cardiomyopathy treated according to the American College of Cardiology/American Heart Association consensus guideline recommendations is not known. The objectives of this study were to define the short- and long-term outcomes of medically refractory obstructive hypertrophic cardiomyopathy patients undergoing alcohol septal ablation (ASA) and surgical septal myectomy (SM) with patient management in accordance with these consensus guidelines, as well as to quantify procedural risk and burden of comorbid conditions at the time of treatment. METHODS AND RESULTS: Patients with obstructive hypertrophic cardiomyopathy referred for either ASA or SM from 2004 to 2015 were followed for the primary end point of short- and long-term mortality and compared with respective age- and sex-matched US populations. Of 477 consecutive severely symptomatic patients, 99 underwent ASA and 378 SM. Compared with SM, ASA patients were older ( P<0.001), had a higher burden of comorbid conditions ( P<0.01), and significantly higher predicted surgical mortality ( P<0.005). Procedure-related mortality was 0.3% and similarly low in both groups (0% in ASA and 0.8% in SM). Over 4.0±2.9 years of follow-up, 95% of patients had substantial improvement in heart failure symptoms to New York Heart Association class I/II (96% in SM and 90% in ASA). Long-term mortality was similar between the 2 groups with no difference compared with age- and sex-matched US populations. CONCLUSIONS: Guideline-based referral for ASA and SM leads to excellent outcomes with low procedural mortality, excellent long-term survival, and improvement in symptoms. These outcomes occur in ASA patients despite being an older cohort with significantly more comorbidities.

Enhanced potency of prasugrel on protease-activated receptors following bivalirudin treatment for PCI as compared to clopidogrel.

ACS patients undergoing percutaneous coronary intervention (PCI) when treated with bivalirudin and clopidogrel had increased frequency of early stent thrombosis. 24 patients referred for intervention with planned bivalirudin therapy, not previously treated with a P2Y12 inhibitor and not receiving heparins or αIIbß3 inhibitors were randomized to treatment with either clopidogrel (600 mg) or prasugrel (60 mg). Platelet aggregation (PA) was measured by light transmission aggregometry (LTA) of platelet-rich plasma in response to ADP, PAR1/PAR4 thrombin receptor agonists and collagen at baseline and at 1, 2, 4 and 16 h following the cessation of bivalirudin infusion. Prasugrel-mediated inhibition of PA was significantly greater than that of clopidogrel at all time points for ADP as well as PAR1. There was an unanticipated, significantly greater protection of PAR4-mediated platelet aggregation only detected with prasugrel and not observed with clopidogrel. We further examined the effect of the hyperreactive PAR4 Thr120 variant in the protease-activated receptor 4 (PAR4), single nucleotide polymorphism (SNP) rs773902 on aggregation protection. The PAR4 protective effect with prasugrel was lost in individuals carrying the PAR4 Thr120 variant, and not in Ala120 homozygote. PAR1, ADP and collagen inhibition was not significantly affected in the hyperreactive PAR4 Thr120 variant. We documented that the P2Y12 ADP receptor-mediated regulation of the strength of the high-affinity conformation of αIIbß3 as detected by PAC-1 ab, and in control of platelet adhesiveness through Rap1 GTPase protein activation. Importantly, the PAR4 Thr120 variant resulted in the increased rate and magnitude of Rap1 activation. Human platelet PAR4 mediated-activation of αIIbß3 was phospholipase C beta (PLCß)-dependent and unlike mouse platelet PI3K-independent. These data identify a PAR4-dependent inhibitory mechanism for the prasugrel-mediated platelet inhibition, not seen with clopidogrel that could explain the reduction in stent thrombosis documented in clinical trials with prasugrel.

Late Clinical Presentation of Prosthesis-Patient Mismatch Following Transcatheter Aortic Valve Replacement.

Prosthesis-patient mismatch (PPM) is relatively common after aortic valve replacement (AVR) and generally is associated with reduced regression of left ventricular (LV) mass. PPM after valve-in-valve transcatheter aortic valve replacement (TAVR) was reported to be 38%. PPM generally is manifested clinically by dyspnea and echocardiographically by high transvalvular gradients. In this E-Challenge, the authors will review a case of a late clinical presentation of PPM 1-year following a valve-in-valve TAVR.