Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program.

BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.

Prospective validation of a risk score to predict pacemaker implantation after transcatheter aortic valve replacement.

INTRODUCTION: The need for pacemaker is a common complication after transcatheter aortic valve replacement (TAVR). We previously described the Emory Risk Score (ERS) to predict the need for new pacemaker implant (PPM) after TAVR. Metrics included in the score are a history of syncope, pre-existing RBBB, QRS duration ≥140 ms, and prosthesis oversizing ≥16%. To prospectively validate the previously described risk score. METHODS: We prospectively evaluated all patients without pre-existing pacemakers, ICD, or pre-existing indications for pacing undergoing TAVR with the Edwards SAPIEN 3 prosthesis at our institution from March 2019 to December 2020 (n = 661). Patients were scored prospectively; however, results were blinded from clinical decision-making. The primary endpoint was PPM at 30 days after TAVR. Performance of the ERS was evaluated using logistic regression, a calibration curve to prior performance, and receiver operating characteristic (ROC) analysis. RESULTS: A total of 48 patients (7.3%) had PPM after TAVR. A higher ERS predicted an increased likelihood of PPM (OR 2.61, 95% CI: 2.05-3.25 per point, p < 0.001). There was good correlation between observed and expected values on the calibration curve (slope = 1.04, calibration at large = 0.001). The area under the ROC curve was 0.81 (95% CI [0.74-0.88], p < 0.001). CONCLUSIONS: The ERS prospectively predicted the need for PPM in a serial, real-world cohort of patients undergoing TAVR with a balloon-expandable prosthesis, confirming findings previously described in retrospective cohorts. Notably, the prospective performance of the score was comparable with that of the initial cohorts. The risk score could serve as a framework for preprocedural risk stratification for PPM after TAVR.

Trends and outcomes of combined percutaneous (TAVI+PCI) and surgical approach (SAVR+CABG) for patients with aortic valve and coronary artery disease: A National Readmission Database (NRD) analysis.

BACKGROUND: In patients with severe aortic stenosis (AS) and concomitant severe coronary artery disease (CAD), the relative merits of a combined percutaneous (transcatheter aortic valve implantation [TAVI] and percutaneous coronary intervention [PCI]] versus surgical approach (surgical aortic valve replacement [SAVR] and coronary artery bypass graft [CABG]) remain unknown. AIMS: To determine the utility of combined percutaneous versus surgical approaches in patients with severe AS and CAD. METHODS: The National Readmission Database (NRD) (2015-2019) was queried to identify all cases of TAVI+PCI and SAVR+CABG. The adjusted odds ratios (aOR) of mortality, stroke, and its composite (major adverse cardiovascular events [MACE]) were calculated using a propensity-score matched (PSM) analysis. RESULTS: A total of 89,314 (5358 TAVI+PCI, 83,956 SAVR+CABG) patients were included in the crude analysis. There was a gradual increase in the utilization of TAVI+PCI from 2016 to 2019 by 2%-4% per year. Using PSM, a subset of 11,361 (5358 TAVI+PCI, 6003 SAVR+CABG) patients with a balanced set of demographics and baseline comorbidities was selected. During index hospitalization, the adjusted odds of MACE (aOR 0.72, 95% confidence interval [CI] 0.62-0.83), and all-cause mortality (aOR 0.68, 95% CI 0.57-0.81) were significantly lower in patients undergoing TAVI+PCI compared with SAVR+CABG. However, patients undergoing TAVI+PCI had a higher incidence of MACE (aOR 1.40, 95% CI 1.05-1.87), and mortality (aOR 1.75, 95% CI 1.22-2.50) at 30-days. The risk of index-admission (aOR 0.82, 95% CI 0.62-1.09) and 30-day (aOR 0.88, 95% CI 0.51-1.51) stroke was similar between the two groups. CONCLUSION: In selected patients with severe AS and concomitant CAD, a combined percutaneous approach (TAVR+PCI) compared with SAVR+CABG may confer a lower risk of MACE and mortality during index admission but a higher incidence of 30-day complications.

Mechanical thrombectomy versus catheter directed thrombolysis in patients with pulmonary embolism: A multicenter experience.

OBJECTIVES: Compare in-hospital outcomes of patients treated with either mechanical thrombectomy (MT) or catheter directed lysis (CDL) in treatment of acute pulmonary embolism (PE). METHODS: This is a multicenter, retrospective cohort study of patients undergoing MT or CDL for acute PE between 2014 and 2021. The primary outcome was the composite of in-hospital death, significant bleed, vascular complication, or need for mechanical support post-procedure. Secondary outcomes included the individual components of the composite outcome in addition to blood transfusions, invasive hemodynamics, echocardiographic data, and intensive care unit (ICU) utilization. RESULTS: 458 patients were treated for PE with 266 patients in the CDL arm and 192 patients in the MT arm. The primary composite endpoint was not significantly different between the two groups with CDL 12% versus MT 11% (p = 0.5). There was a significant difference in total length of ICU time required with more in the CDL group versus MT (3.8 ± 2.0 vs. 2.8 ± 3.0 days, p = 0.009). All other secondary end points showed no significant difference between the groups. CONCLUSIONS: In patients undergoing catheter directed treatment of PE, there was no difference between MT and CDL in terms of in-hospital mortality, bleeds, catheter-related complications, and hemodynamics.

Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial.

Importance: Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. Objective: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Design, Setting, and Participants: Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Interventions: Ultrasound renal denervation vs a sham procedure. Main Outcomes and Measures: The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Results: Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. Conclusions and Relevance: In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT03614260.

Update on Minimalist TAVR Care Pathways: Approaches to Care in 2022.

PURPOSE OF REVIEW: This review summarizes current data supporting a minimalist TAVR approach and identifies the need for additional study to optimize TAVR care. The authors discuss future directions of the TAVR landscape and how this necessitates evolution of minimalist care pathways. RECENT FINDINGS: Transcatheter aortic valve replacement (TAVR) has become a mainstay in the treatment of aortic stenosis since the initial procedure in 2002. Recently, attention has shifted to TAVR optimization and the minimalist approach with a focus on minimizing procedural sedation, protocolization of perioperative management, and prioritization on early discharge. This approach has been shown to be safe and reduce procedure time, length of stay, and overall cost for hospital systems. The minimalist care pathway avoids general anesthesia, shortens procedure time and length of stay, and reduces cost without changing mortality or readmission rates at 30 days. A variety of protocols have been proposed without a clear consensus on specific components or patient eligibility. There is a continued need for data regarding patient risk stratification, valve selection, and discharge strategy as TAVR becomes increasingly common.

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial.

BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.

A single healthcare experience with Impella RP.

OBJECTIVES: To understand the predictors of survival and indications for Impella RP in a single healthcare experience. BACKGROUND: The Impella RP can be used to temporarily support patients with right ventricular (RV) dysfunction after left ventricular assist device (LVAD) placement or myocardial infarction (MI). However, recent postmarket approval data have raised concerns of higher than expected mortality with this device. METHODS: A retrospective chart review and analysis of all patients that underwent Impella RP placement in the Emory Healthcare system between January 2016 and December 2018 were performed. Patients were classified according to the indication. RESULTS: A total of 39 patients underwent Impella RP placement. Six patients were post-LVAD, 9 were implanted for massive pulmonary embolism with persistent shock, 8 for postcardiac surgery RV failure (non-LVAD), 11 for RV failure post-MI, and 5 for new or worsening nonischemic cardiomyopathy. The worst survival was noted in MI-related cardiogenic shock group and in patients who presented with cardiac arrest (3/12). All observed deaths were due to persistent refractory shock. There was no device related death. Survival improved during the last year of experience compared to the first 2 years. CONCLUSION: This study supports the selective use of the Impella RP, with a higher than national reported survival rate (49% vs. 28.6%). Indication appears to be an important factor determining survival.

Safety of same-day discharge after uncomplicated, minimalist transcatheter aortic valve replacement in the COVID-19 era.

OBJECTIVES: We sought to evaluate the safety, efficacy and feasibility of same-day discharge after uncomplicated, minimalist TAVR. BACKGROUND: At the start of the COVID-19 pandemic, we created a same-day discharge (SDD) pathway after conscious sedation, transfemoral (minimalist) TAVR to help minimize risk of viral transmission and conserve hospital resources. Studies support that next-day discharge (NDD) for carefully selected patients following minimalist TAVR is safe and feasible. There is a paucity of data regarding the safety of SDD after TAVR. METHODS: In-hospital and 30 day outcomes of consecutive patients meeting pre-specified criteria for SDD after minimalist TAVR at our institution between March and July of 2020 were reviewed. Outcomes were compared to a NDD cohort from July 2018 through July 2020 that would have met SDD criteria. Primary endpoints were mortality, delayed pacemaker placement, stroke and cardiovascular readmission at 30 days. RESULTS: Twenty nine patients were discharged via the SDD pathway after TAVR. 128 prior NDD patients were identified who met all criteria for SDD. The STS scores were similar between the two groups (SDD 2.6% ±1.5 vs. NDD 2.3% ± 1.2). There were no deaths at 30 days in either group. There was no significant difference in delayed pacemaker placement (SDD 0% vs. NDD 0.8%, p > .99) or cardiovascular readmission (SDD 0% vs. NDD 5.5%, p = .35) at 30 days. CONCLUSIONS: Same day discharge following uncomplicated, minimalist TAVR in selected patients appears to be safe, achieving similar 30 day outcomes as a cohort of next day discharge patients.

Adverse clinical outcomes in patients undergoing both PCI and TAVR: Analysis from a pooled multi-center registry.

BACKGROUND: There is a paucity of data regarding the optimum timing of PCI in relation to TAVR. OBJECTIVE: We compared the major adverse cardiovascular and cerebrovascular events (MACCE) rates among patients who underwent percutaneous coronary intervention (PCI) before transcatheter aortic valve replacement (TAVR) with those who received PCI with/after TAVR. METHODS: In this multicenter study, we pooled all consecutive patients who underwent TAVR at three high volume centers. RESULTS: Among 3,982 patients who underwent TAVR, 327 (8%) patients underwent PCI within 1 year before TAVR, 38 (1%) had PCI the same day as TAVR and 15 (0.5%) had PCI within 2 months after TAVR. Overall, among patients who received both PCI and TAVR (n = 380), history of previous CABG (HR:0.501; p = .001), higher BMI at TAVR (HR:0.970; p = .038), and statin therapy after TAVR (HR:0.660, p = .037) were independently associated with lower MACCE while warfarin therapy after TAVR was associated with a higher risk of MACCE (HR:1.779, p = .017). Patients who received PCI within 1 year before TAVR had similar baseline demographics, STS scores, clinical risk factors when compared to patients receiving PCI with/after TAVR. Both groups were similar in PCI (Syntax Score, ACC/AHA lesion class) and TAVR (valve types, access) related variables. There were no significant differences in terms of MACCE (log rank p = .550), all-cause mortality (log rank p = .433), strokes (log rank p = .153), and repeat PCI (log rank p = .054) in patients who underwent PCI with/after TAVR when compared to patients who received PCI before TAVR. CONCLUSION: Among patients who underwent both PCI and TAVR, history of CABG, higher BMI, and statin therapy had lower, while those discharged on warfarin, had higher adverse event rates. Adverse events rates were similar regardless of timing of PCI.

Temporal trends and outcomes in utilisation of transcatheter and surgical aortic valve therapies in aortic valve stenosis patients with heart failure.

INTRODUCTIONS & AIMS: Heart failure (HF) is a common comorbidity in patients undergoing surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). We sought to access the temporal trends and outcomes of TAVR or SAVR in HF patients. METHOD: The NIS database from 2011-2014 was queried for patients that underwent TAVR or SAVR and were subsequently diagnosed with HF. Temporal trends in the utilisation of TAVR or SAVR in HF patients were analysed. RESULTS: Among 27 982 patients who were diagnosed with HF of whom 17 681 (63.2%) had heart failure with reduced ejection fraction (HFrEF) while 10 301 (36.8%) had heart failure with preserved ejection fraction (HFpEF), 9049 (32.3%) underwent TAVR and 16 933 (76.7%) underwent SAVR. Patients with HFrEF and HFpEF had higher utilisation of TAVR compared with SAVR over the course of the study period (P trend < .001). TAVR was associated with lower mortality [2.8% in 2012 and 1.8% in 2014 (P .013)] compared with SAVR. Similarly, multiple logistic regression showed a statistically significant lower in-hospital mortality in the TAVR group compared with SAVR (aOR 0.634; CI 0.504, 0.798, P < .001). CONCLUSION: For patients with severe aortic valve stenosis and heart failure who undergo aortic valve intervention, TAVR is associated with less odds of in-hospital mortality compared with SAVR.

Hot topics in interventional cardiology: Proceedings from the society for cardiovascular angiography and interventions 2020 think tank.

The society for cardiovascular angiography and interventions (SCAI) think tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community for high-level field-wide discussions. The 2020 think tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease (CHD). Each session was moderated by a senior content expert and co-moderated by a member of SCAI's emerging leader mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialogue from a broader base, and thereby aid SCAI and the industry community in developing specific action items to move these areas forward.

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

BACKGROUND: Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. METHODS: SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. FINDINGS: Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. INTERPRETATION: Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. FUNDING: Medtronic.

Degenerative mitral regurgitation predicts worse outcomes in patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: To evaluate the role mitral regurgitation (MR) etiology and severity play in outcomes for patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Multiple prior studies have investigated the influence of MR severity on outcomes for patients undergoing TAVR. Less has been published regarding the effects of MR etiology on outcomes, including its impact on heart failure hospitalization. METHODS: Two hundred and seventy patients undergoing TAVR at 2 hospitals were enrolled. Each patient had a baseline and follow-up (within 30 days of TAVR) echocardiogram that was analyzed. MR was graded as none, mild, moderate, or severe, as well as functional or degenerative. We compared patient outcomes, including death and heart failure hospitalization, among none-mild MR, moderate-severe functional MR, and moderate-severe degenerative MR groups. RESULTS: Two hundred and seventy patients underwent TAVR, reducing mean aortic valve gradients from 45 ± 15 mm Hg to 9 ± 4 mm Hg. On multivariable analysis, only patients with moderate-severe degenerative MR had decreased survival free of death or CHF hospitalization compared to those with none-mild MR (P = .011). Subanalysis showed patients with moderate-severe degenerative MR were more likely to be hospitalized for heart failure at 2 years compared to those with moderate-severe functional MR (P = .02). Patients with moderate-severe degenerative MR were also less likely to have improvement in MR severity at follow up (P = .01). CONCLUSIONS: Special consideration should be given to patients with moderate-severe degenerative MR undergoing TAVR. As transcatheter approaches for mitral valve repair and replacement continue to evolve, moderate-severe degenerative MR patients may benefit from consideration of double valve intervention.

Understanding preferences regarding consent for pragmatic trials in acute care.

BACKGROUND: There has been debate about the role of consent in pragmatic trials comparing qualitatively similar interventions. Consent preferences may differ in acute care contexts, given severe illness, time constraints, and other barriers to consent. In addition, studies have not assessed the impact of disclosing financial considerations as a justification for trials. This study was designed to assess preferences of the general public regarding consent for a pragmatic trial in ST-elevation myocardial infarction. METHODS: This survey was completed using an online, probability-based panel representative of the US population. It incorporated a randomized, experimental (2 × 2) design assessing (1) preference for written consent versus an alternative (notification after enrollment or brief verbal consent) and (2) impact of including cost as a motivating factor for the trial. The survey used a scenario based on a recent pragmatic trial in ST-elevation myocardial infarction. Primary independent variables were personal preference and recommendation as a member of a review board regarding written consent versus the assigned alternative strategy and personal attitude toward trial enrollment. Descriptive analyses were conducted using post-stratification weights. Regression models were created to examine relationships between demographic variables and consent preference and willingness to enroll. Provision of cost information was incorporated into a regression model to examine its impact on consent preference. RESULTS: The study included 2027 participants. Of those participants, 51.1% versus 45.8% stated a personal preference for written consent versus notification after enrollment; however, 60.0% versus 35.5% preferred brief verbal consent to written consent. Even among respondents stating they would be unlikely to enroll in the trial if asked, more respondents (50.6%) preferred brief verbal consent. The preference for verbal consent was generally shared across demographic categories, although lower educational attainment was associated with reduced acceptance (p = 0.001 for trend). Respondents were more likely to support an alternative to written consent when asked their personal preference than when asked their recommendation as a member of a review board. The provision of cost information did not have a meaningful effect on consent preferences, attitudes toward enrollment, or views about the study. CONCLUSION: Respondents generally supported prospective involvement in enrollment decisions in the setting of acute myocardial infarction and were particularly supportive of brief verbal consent. This support persisted across demographic categories. The finding that individuals were more likely to support alternatives to written consent when asked for a personal preference rather than as a "committee member" suggests that conservative institutional approaches to consent could hinder implementation of more patient-centered approaches. The role of cost transparency in consent discussions warrants further study.

Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve demonstrates good 30 day clinical outcomes in patients with severe aortic stenosis who are at intermediate risk of surgical mortality. Here we report longer-term data in intermediate-risk patients given SAPIEN 3 TAVR and compare outcomes to those of intermediate-risk patients given surgical aortic valve replacement. METHODS: In the SAPIEN 3 observational study, 1077 intermediate-risk patients at 51 sites in the USA and Canada were assigned to receive TAVR with the SAPIEN 3 valve [952 [88%] via transfemoral access) between Feb 17, 2014, and Sept 3, 2014. In this population we assessed all-cause mortality and incidence of strokes, re-intervention, and aortic valve regurgitation at 1 year after implantation. Then we compared 1 year outcomes in this population with those for intermediate-risk patients treated with surgical valve replacement in the PARTNER 2A trial between Dec 23, 2011, and Nov 6, 2013, using a prespecified propensity score analysis to account for between-trial differences in baseline characteristics. The clinical events committee and echocardiographic core laboratory methods were the same for both studies. The primary endpoint was the composite of death from any cause, all strokes, and incidence of moderate or severe aortic regurgitation. We did non-inferiority (margin 7·5%) and superiority analyses in propensity score quintiles to calculate pooled weighted proportion differences for outcomes. FINDINGS: At 1 year follow-up of the SAPIEN 3 observational study, 79 of 1077 patients who initiated the TAVR procedure had died (all-cause mortality 7·4%; 6·5% in the transfemoral access subgroup), and disabling strokes had occurred in 24 (2%), aortic valve re-intervention in six (1%), and moderate or severe paravalvular regurgitation in 13 (2%). In the propensity-score analysis we included 963 patients treated with SAPIEN 3 TAVR and 747 with surgical valve replacement. For the primary composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation, TAVR was both non-inferior (pooled weighted proportion difference of -9·2%; 90% CI -12·4 to -6; p<0·0001) and superior (-9·2%, 95% CI -13·0 to -5·4; p<0·0001) to surgical valve replacement. INTERPRETATION: TAVR with SAPIEN 3 in intermediate-risk patients with severe aortic stenosis is associated with low mortality, strokes, and regurgitation at 1 year. The propensity score analysis indicates a significant superiority for our composite outcome with TAVR compared with surgery, suggesting that TAVR might be the preferred treatment alternative in intermediate-risk patients. FUNDING: None.

Safety of catheter-directed thrombolysis for massive and submassive pulmonary embolism: Results of a multicenter registry and meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) in the treatment of acute pulmonary embolism (PE). BACKGROUND: The use of CDT for the treatment of acute submassive and massive PE is increasing in frequency. However, its safety and efficacy have not been well elucidated. METHODS: This study is made of two parts: one is a two-center registry of acute PE patients treated with CDT. The safety outcome evaluated was any major complication including fatal, intracranial (ICH), intraocular, or retroperitoneal hemorrhage or any overt bleeding requiring transfusion or surgical repair. The efficacy outcome was acute change in invasive pulmonary artery systolic pressure (PASP). The second part is a meta-analysis of all contemporary studies that used CDT for PE. Reported outcomes are the same as in the registry, with the addition of right ventricular to left ventricular (RV/LV) ratio change. RESULTS: In the registry, 137 patients were included (age 59 ± 15, 50% male, 88% submassive PE). ICH occurred in two patients and major complications in 13 (9.4%). PASP decreased post procedure by 19 ± 15 mm Hg (95% CI 16-23). In the meta-analysis, 16 studies were included with 860 patients. Rate of ICH was 0.35% and the major complication rate was 4.65%, most requiring transfusion only. In-hospital mortality was 12.9% in the massive and 0.74% in the submassive group. All studies showed improvement in PASP and/or RV/LV ratio post CDT. CONCLUSIONS: CDT is associated with a low major complication rate. Randomized studies are needed to evaluate its efficacy relative to anticoagulation alone. © 2017 Wiley Periodicals, Inc.

End-stage renal disease and severe aortic stenosis: Does valve replacement improve one-year outcomes?

BACKGROUND: Treatment for patients with end-stage renal disease (ESRD) and severe aortic stenosis (AS) includes balloon aortic valvuloplasty (BAV), surgical (SAVR), or transcatheter (TAVR) aortic valve replacement. We compared outcomes among these strategies. METHODS: A retrospective review of patients with ESRD undergoing treatment for severe AS between 07/2007 and 06/2015 was performed at our center. Patients were classified based on treatment: BAV-only, TAVR, or SAVR. Baseline characteristics and 30-day outcomes were compared among groups. A 1-year survival analysis was performed. RESULTS: Of 85 patients, 25 (29.4%) underwent BAV, 30 (35.3%) TAVR, and 30 (35.3%) SAVR. Patients in the SAVR group, compared to the BAV or TAVR patients, were younger (63 vs. 74 vs. 71 years, P = 0.02) and had less prior stroke (3.3% vs. 12.0% vs. 30.0%, P = 0.008). While all BAV patients had NYHA class III/IV, 93.3% and 76.7% of patients had NYHA class III/IV in the TAVR and SAVR group, respectively (P = 0.001). BAV patients were less likely to have atrial fibrillation than TAVR or SAVR patients (16.0% vs. 43.3% vs. 50.0%, P = 0.03). All patients were high risk, but there was a statistical trend to lower STS scores in the SAVR group (8.6% vs. 13.5% vs. 13.5%, P = 0.08). There was no significant difference in 30-day mortality (16.7% vs. 10.0% vs. 10.0%, P = 0.74), but BAV treated patients had an increased 1-year mortality compared to those treated with TAVR or SAVR (87.0% vs. 32.0%, vs. 36.7%, P=<0.001). Independent predictors of 1-year mortality were a higher STS score (HR 1.026, 95%CI 1.002-1.051) and BAV-only strategy (BAV vs. TAVR: HR 3.961, 95%CI 1.595-9.840), but dialysis duration and type, and SAVR versus TAVR were not. CONCLUSIONS: Patients with ESRD and severe AS have a similar and higher survival with TAVR or SAVR when compared to BAV at 1-year. These results may influence patient care decisions favoring valve replacement in AS patients with ESRD. © 2016 Wiley Periodicals, Inc.

Anatomical risk models for paravalvular leak and landing zone complications for balloon-expandable transcatheter aortic valve replacement.

BACKGROUND: Though several anatomical characteristics have been reported separately as risk factors for paravalvular leak (PVL) and landing zone (LZ) complications after transcatheter aortic valve replacement (TAVR), multivariate risk models are needed. METHODS: Patients that underwent balloon-expandable TAVR with multidetector cardiac computed tomography (MDCT) sizing were studied. MDCT images were analyzed and the association between anatomical factors and ≥mild PVL, ≥moderate PVL, and LZ complications (annular rupture, requirement of new permanent pacemaker, and coronary obstruction) was determined, and subsequently competing predictive models were developed and validated. RESULTS: A total of 316 consecutive TAVR patients were included. Median age was 82.0 years (74.0-87.0) and STS score was 8.3% (5.4-10.9). Factors associated with ≥mild PVL included TAVR with Sapien/Sapien XT vs. Sapien 3 (OR = 2.50, 95% CI = 1.24-5.07), LVOT nontubularity (OR = 1.02, 95% CI = 1.01-1.04), LZ calcification (OR = 1.01, 95% CI = 1.00-1.01), and low cover index (OR = 0.94, 95% CI = 0.91-0.96). Factors associated with LZ complications included LZ calcification (OR = 1.01, 95% CI 1.00-1.01), leaflet asymmetry (OR = 1.01, 95% CI 1.01-1.02), and cover index (OR = 1.09, 95% CI 1.03-1.14). Predictive models for ≥mild PVL (AUC = 0.71, 95% CI = 0.66-0.77), ≥moderate PVL (AUC = 0.75, 95% CI = 0.65-0.84), and LZ complications (AUC = 0.77, 95% CI = 0.67-0.87) were created using procedural details and anatomical data from the MDCT. Clinical variables were not included as they were poorly correlated with the occurrence of PVL and LZ complications. For each outcome, the area under the curve (AUC) of the multivariate model was superior to the model consisting only of individual factors. CONCLUSIONS: A model using procedural/anatomical characteristics derived from MDCT predicts ≥mild PVL, ≥moderate PVL, and LZ complications post-TAVR. Incorporation of anatomical risks into clinical practice may help stratify patients before TAVR. © 2017 Wiley Periodicals, Inc.

Does minimalist transfemoral transcatheter aortic valve replacement produce better survival in patients with severe chronic obstructive pulmonary disease?

OBJECTIVES: To compare outcomes after minimalist and standard transfemoral transcatheter aortic valve replacement (TF-TAVR) in patients with severe chronic obstructive pulmonary disease (COPD). BACKGROUND: TF-TAVR is increasingly performed with conscious sedation and transthoracic echocardiography guidance (minimalist). The safety/efficacy of this technique in patients with severe COPD is unknown. METHODS: We compared demographics, 30-day outcomes and 1-year survival of patients with severe COPD (FEV1% ≤50) who underwent minimalist vs. standard TF-TAVR between 2008 and 2015 at our institution. RESULTS: Of 88 patients with severe COPD, 46 underwent minimalist and 42 underwent standard TF-TAVR. There were no differences on baseline characteristics, except for more history of coronary artery bypass grafting (45.5% vs. 20.6%, P = 0.03) and less history of cerebrovascular disease (16.7% vs. 45.5%, P = 0.03) in the standard TF-TAVR. Seventeen minimalist TF-TAVR patients (41.0%) were transferred directly to the general medical ward with telemetry monitoring (without ICU stay); all standard TF-TAVR patients went to the ICU. Minimalist TF-TAVR patients had shorter procedure time (97 vs. 129 min, P < 0.001), ICU time (21.8 vs. 29.8 hr, P = 0.001) and length of stay (2 vs. 5 days, P = 0.001). There were no differences in procedure complications and 30-day mortality between groups. In our multivariate analysis, minimalist TF-TAVR (HR 0.28, 95%CI 0.08-0.97) and previous coronary revascularization (HR 0.24, 95%CI 0.09-0.65) were associated with increased 1-year survival. In contrast, moderate paravalvular leak (HR 7.73, 95%CI 1.94-30.84) was associated with decreased 1-year survival. CONCLUSION: In patients with severe COPD, Minimalist TF-TAVR results in less resource utilization and improved 1-year survival compared to standard approach. Our findings should be validated in a larger cohort of patients with severe COPD. © 2016 Wiley Periodicals, Inc.