Outcomes Of Intermediate-risk Patients Research Articles

Outcomes of SAPIEN 3 Transcatheter Aortic Valve Replacement Compared With Surgical Valve Replacement in Intermediate-Risk Patients

BackgroundPrevious studies demonstrated transcatheter aortic valve replacement (TAVR) with an earlier generation balloon-expandable valve to be noninferior to surgical aortic valve replacement (SAVR) for death and disabling stroke in intermediate-risk patients with symptomatic, severe aortic stenosis at 5 years. However, limited long-term data are available with the more contemporary SAPIEN 3 (S3) bioprosthesis. ObjectivesThe aim of this study was to compare 5-year risk-adjusted outcomes in intermediate-risk patients undergoing S3 TAVR vs SAVR. MethodsPropensity score matching was performed to account for baseline differences in intermediate-risk patients undergoing S3 TAVR in the PARTNER 2 (Placement of Aortic Transcatheter Valves) S3 single-arm study and SAVR in the PARTNER 2A randomized clinical trial. The primary composite endpoint consisted of 5-year all-cause death and disabling stroke. ResultsA total of 783 matched pairs of intermediate-risk patients with severe aortic stenosis were studied. There were no differences in the primary endpoint between S3 TAVR and SAVR at 5 years (40.2% vs 42.7%; HR: 0.87; 95% CI: 0.74-1.03; P = 0.10). The incidence of mild or greater paravalvular regurgitation was more common after S3 TAVR. There were no differences in structural valve deterioration–related stage 2 and 3 hemodynamic valve deterioration or bioprosthetic valve failure. ConclusionsIn this propensity-matched analysis of intermediate-risk patients, 5-year rates of death and disabling stroke were similar between S3 TAVR and SAVR. Rates of structural valve deterioration–related hemodynamic valve deterioration were similar, but paravalvular regurgitation was more common after S3 TAVR. Longer-term follow-up is needed to further evaluate differences in late adverse clinical events and bioprosthetic valve durability. (PII S3i [PARTNER II Trial: Placement of Aortic Transcatheter Valves II – S3 Intermediate], NCT03222128; PII A (PARTNER II Trial: Placement of Aortic Transcatheter Valves II – XT Intermediate and High Risk], NCT01314313)

Depth of Response to Intensive Chemotherapy Has Significant Prognostic Value among Acute Myeloid Leukemia (AML) Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation with Intermediate or Adverse Risk at Diagnosis Compared to At-Risk Group According to European Leukemia Net 2017 Risk Stratification.

Simple SummaryAcute myeloid leukemia (AML) is a devastating but potentially curable disease. The updated version of the European Leukemia Net (ELN) 2017 genetic risk stratification is used as the standard for the prognosis and classification of AML. In the present study, we evaluated the prognostic value of the ELN 2017 criteria on post-hematopoietic stem-cell transplantation (HSCT) outcomes and compared it with pre-HSCT measurable residual disease (MRD) status, determined by Wilms tumor gene 1 (WT1) expression. We classified the patients as intermediate (INT) risk and adverse (ADV) risk. We found that the ELN 2017 risk classification did not effectively predict post-HSCT outcomes in patients with INT or ADV risk. The pre-HSCT WT1 level predicted post-HSCT relapse better than ELN 2017 and had a more prominent prognostic value in the ELN INT risk group than in the ADV risk group.We evaluated the prognostic efficiency of the European Leukemia Net (ELN) 2017 criteria on the post-transplant outcomes of 174 patients with intermediate (INT; n = 108, 62%) or adverse (ADV) risk (n = 66, 38%) of acute myeloid leukemia; these patients had received the first allogeneic hematopoietic stem-cell transplantation (HSCT) at remission. After a median follow-up period of 18 months, the 2 year OS, RFS, and CIR after HSCT were estimated to be 58.6% vs. 64.4% (p = 0.299), 50.5% vs. 53.7% (p = 0.533), and 26.9% vs. 36.9% (p = 0.060) in the INT and ADV risk groups, respectively. Compared to the ELN 2017 stratification, pre-HSCT WT1 levels (cutoff: 250 copies/104 ABL) more effectively segregated the post-HSCT outcomes of INT risk patients compared to ADV risk patients regarding their 2 year OS (64.2% vs. 51.5%, p = 0.099), RFS (59.4% vs. 32.4%, p = 0.003), and CIR (18.9% vs. 60.0% p < 0.001). Indeed, high WT1 levels were more prominent in INT risk patients than in ADV risk patients. Notably, FLT3-ITD had the greatest impact on post-HSCT outcomes among all the ELN 2017 criteria components; patients in the FLT3-ITD mutant subgroups exhibited the worst outcomes regardless of their allelic ratios or NPM1 status compared to the pre-HSCT WT1 level of other INT and ADV risk patients.

Active surveillance in favorable intermediate risk prostate cancer: outstanding questions and controversies.

Active surveillance has become the preferred management strategy for patients with low risk prostate cancer, but it is unclear if active surveillance can be safely extended to favorable intermediate risk (FIR) prostate cancer patients. Furthermore, defining a favorable intermediate risk prostate cancer population safe for active surveillance remains elusive due to paucity of high-level data in this population. This article serves to review relevant data, particularly the safety of active surveillance in grade group 2 patients, and what tools are available to aid in selecting a favorable subset of intermediate risk patients. Active surveillance studies with long-term data appear to report worsened survival outcomes in intermediate risk patients when compared to those undergoing definitive treatment, but there exists a subset of intermediate risk patients with nearly equivalent outcomes to low risk patients on active surveillance. Tools such as percentage and total length of Gleason pattern 4, tumor volume, prostate specific antigen density, magnetic resonance imaging, and genomic modifiers may help to select a favorable subset of intermediate risk prostate cancer appropriate for active surveillance. Active surveillance is a viable strategy in select patients with low volume group grade 2 (GG2) prostate cancer. Prospective and retrospective data in the FIR population appear to be mostly favorable in regards to survival outcomes, but there exists some heterogeneity with respect to long-term outcomes in this patient population.

Hemodynamic Outcome at 5y of the Perceval Sutureless Valve: Results from an International Prospective Trial

Objective: To report the 5-year hemodynamic and clinical outcomes in intermediate risk patients implanted with the Perceval sutureless aortic valve.Methods: During 2010-2013, 658 patients were enro...

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

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. 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. 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. ClinicalTrials.gov #NCT01314313 and NCT03222128.

Sex-Specific Outcomes of Transcatheter Aortic Valve Replacement With the SAPIEN 3 Valve: Insights From the PARTNER II S3 High-Risk and Intermediate-Risk Cohorts

ObjectivesThe purpose of this study was to identify sex-specific outcomes of intermediate risk patients undergoing transcatheter aortic valve replacement with the SAPIEN 3 valve. BackgroundA survival difference has been observed in women as compared with men in inoperable and high-risk patients receiving early-generation balloon-expandable valves for transcatheter aortic valve replacement (TAVR). Whether a sex-specific outcome difference persists with newer-generation valves and in lower-risk patients is unknown. MethodsThe PARTNER (Placement of Aortic Transcatheter Valves) II S3 trial included high-risk (HR) (Society of Thoracic Surgeons risk score >8% or heart team determination) and intermediate-risk (IR) (Society of Thoracic Surgeons risk score 4% to 8% or heart team determination) patients with severe symptomatic aortic stenosis who were treated with TAVR with the SAPIEN 3 valve. Patient characteristics and clinical outcomes at 30 days and 1 year were compared by sex. ResultsBetween October 2013 and December 2014, 1,661 patients were enrolled: 583 were HR (338 men, 245 women) and 1,078 were IR (666 men, 412 women). In both cohorts, women were more likely than men to be frail (22% vs. 13%; p < 0.001), but less likely to have comorbid conditions of renal insufficiency, coronary artery disease, atrial fibrillation, or chronic obstructive pulmonary disease. Women were more likely to receive ≤23-mm valves (74.1% vs. 11.1%; p < 0.001) and were less likely to receive 29-mm valves (1.4% vs. 35.1%; p < 0.001). In the combined cohorts, there was no difference in mortality for women compared with men at 30 days (2.0% vs. 1.2%; p = 0.20) or 1 year (9.3% vs. 10.2%; p = 0.59). There were no differences in disabling stroke or any stroke at 30 days or 1 year; however, women had an increased rate of minor stroke at 30 days (2.1% vs. 0.7%; p = 0.01). Female sex was associated with increased major vascular complications (7.9% vs. 4.4%; p = 0.003), but not with moderate or severe paravalvular regurgitation. Notably, similar outcomes regarding sex-specific outcomes were obtained within stratified analyses of the HR and IR cohorts. ConclusionsThe study found no apparent sex-specific differences in survival or stroke in this trial of TAVR. This may reflect the changing demographic of patients enrolled, use of newer-generation valves with more sizes available, and more accurate valve sizing techniques.

Transcatheter Aortic Valve Replacement: Outcomes, Indications, Complications, and Innovations.

Transcatheter aortic valve replacement (TAVR) has become the standard of care for the treatment of severe aortic stenosis in individuals who are at prohibitive surgical risk and presents a viable alternative to surgery in selected patients who are at high operative risk. To date, outcomes from the PARTNER (Placement of AoRtic TraNscathetER Valve) and Medtronic CoreValve® US Pivotal trials continue to show the benefits of TAVR in these high-risk subgroups out to 5 and 3years, respectively (as reported by Mack et al. Lancet. 85:2477-2484 2015; Kapadia et al. Lancet. 385:2485-2491 2015; Deeb et al. J Am Coll Cardiol. 67:2565-2574 2016). Furthermore, the recent release of the PARTNER-2 and SURTAVI trial results among other international data suggest that clinical outcomes for intermediate risk patients may be promising for TAVR compared to surgical aortic valve replacement (SAVR) (as reported by Leon et al. N Engl J Med. 374:1609-1620 2016; Reardon et al. N Engl J Med. 376:1321-1331 2017). However, several questions persist regarding TAVR-specific complications as well as long-term durability. Paravalvular regurgitation, permanent pacemaker implantation, stroke, vascular access injury, and renal failure in post-TAVR patients remain adversaries in the quest to perfect this groundbreaking, game-changing technology (as reported by Khatri et al. Ann Intern Med. 158:35-46 2013). In this review, we provide an up-to-date synopsis of results from landmark clinical trials that cumulatively attest to the comparability of TAVR to best medical therapy and SAVR in extreme-risk, high-risk, and intermediate-risk patient populations. We continue with a review of studies that seek to compare transcatheter vs. surgical valve implantation in lower-risk subgroups. We also introduce ongoing efforts to optimize the peri-procedural management of TAVR and conclude with a presentation of management strategies and new generation valve platforms that seek to address some of the current limitations of transcatheter valve implantation.

Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients

BackgroundAlthough transcatheter aortic-valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk.MethodsWe evaluated the clinical outcomes in intermediate-risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self-expanding prosthesis) with surgical aortic-valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic-valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement.ResultsA total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 79.8±6.2 years, and all were at intermediate risk for surgery (Society of Thoracic Surgeons Predicted Risk of Mortality, 4.5±1.6%). At 24 months, the estimated incidence of the primary end point was 12.6% in the TAVR group and 14.0% in the surgery group (95% credible interval [Bayesian analysis] for difference, −5.2 to 2.3%; posterior probability of noninferiority, >0.999). Surgery was associated with higher rates of acute kidney injury, atrial fibrillation, and transfusion requirements, whereas TAVR had higher rates of residual aortic regurgitation and need for pacemaker implantation. TAVR resulted in lower mean gradients and larger aortic-valve areas than surgery. Structural valve deterioration at 24 months did not occur in either group.ConclusionsTAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure. (Funded by Medtronic; SURTAVI ClinicalTrials.gov number, NCT01586910.)

Use of low density lipoprotein particle number levels as an aid in statin treatment decisions for intermediate risk patients: a cost-effectiveness analysis.

BackgroundThe 2013 ACC/AHA guideline recommended either no statin therapy or moderate-intensity statin therapy (MST) for intermediate risk patients—those with 5–7.5% 10-year risk and without cardiovascular disease (CVD), hypercholesterolemia or diabetes. The guideline further suggested that the therapy choice be based on patient-clinician discussions of risks and benefits. Since low-density lipoprotein particle (LDL-P) levels were reported to be associated with CVD independently of traditional risk factors in intermediate and low risk patients, we investigated the cost-effectiveness of using LDL-P levels to identify intermediate risk patients likely to benefit from initiating or intensifying statin therapy.MethodsWe evaluated 5 care strategies for intermediate risk patients. These included the strategies suggested by the guideline: no-statin therapy and MST. We compared each of these strategies to a related strategy that incorporated LDL-P testing. No-statin therapy was compared with the strategy of MST for those with high LDL-P levels and no statin therapy for all other patients (test-and-MST). MST was compared with the strategy of high-intensity statin therapy (HST) for those with high LDL-P levels and MST for all other patients (test-and-HST). We also evaluated the strategy of HST for all. Costs (payer perspective) and utilities were assessed over a 5-year time horizon in a Markov model of 100,000 hypothetical intermediate risk patients.ResultsHST dominated all other strategies, costing less and—despite causing 739 more cases of diabetes than did MST—resulting in more quality adjusted life-years (QALYs). For patient-clinician discussions that would otherwise lead to the MST strategy, we found the test-and-HST strategy reduced costs by $4.67 MM and resulted in 134 fewer CVD events and 115 additional QALYs. For patient-clinician discussions that would otherwise lead to no statin therapy, we found that the test-and-MST strategy reduced costs by $3.25 MM, resulted in 97 fewer CVD events and 44 additional QALYs.ConclusionsThe HST strategy was cost saving and improved outcomes in intermediate risk patients. For patient and clinicians concerned about the adverse events associated with HST, using LDL-P levels to target intensified statin therapy could improve outcomes and reduce costs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0429-6) contains supplementary material, which is available to authorized users.

TCT-679 Diabetes and Clinical Outcomes in Intermediate Risk Patients Randomized to Transcatheter Versus Surgical Aortic Valve Replacement: An Analysis of the PARTNER 2A Trial

TCT-679 Diabetes and Clinical Outcomes in Intermediate Risk Patients Randomized to Transcatheter Versus Surgical Aortic Valve Replacement: An Analysis of the PARTNER 2A Trial

TCT-681 SOLACE AU Study: Interim results at one year of the Edwards SAPIEN XT TM Transcatheter Heart Valve in intermediate risk patients with severe aortic stenosis in Australia

We report the clinical outcomes of intermediate-risk patients at one year from the SOLACE AU Registry who received the Edwards SAPIEN XT TM Transcatheter Heart Valve (THV). This is a single arm multi-centre study in 11 centres throughout Australia of select symptomatic patients with severe aortic

Transapical vs. transfemoral aortic valve implantation: Which approach for which patient, from a surgeon's standpoint.

Transcatheter aortic valve implantation (TAVI) has gained increasing acceptance for treating patients with severe aortic stenosis (AS), especially in the presence of a higher risk profile. The procedure is performed a number of ways, however, the two main routes of access are the transfemoral (TF) retrograde approach and the transapical (TA) antegrade approach. At the present time TAVI is indicated in the presence of high risk according to current position statements from the European Society Cardiology and European Association Cardiothoracic Surgery (1). TAVI outcomes in intermediate risk patients, presenting with a logistic EuroSCORE lower than 20% or a Society of Thoracic Surgeons (STS) Score between 4% and 8% are currently being evaluated in prospective randomized trials such as the SURTAVI trial (TF CoreValve™ versus conventional surgery) and PARTNER 2 trial (Edwards SAPIEN-XT™ versus conventional surgery). Despite these advancements in endovascular approaches, conventional surgery remains the standard for many patients and is associated with excellent outcomes. For example, in 2011 a German registry reported an overall mortality to be as low as 3% in 11,500 patients undergoing conventional surgery for aortic valve disease (2). Our common goal is to perform the optimal therapy for an individual patient. This is fundamentally based on a low procedural risk together with immediate functional improvement and good longer term durability. Simplicity and safety will usually lead to good acceptance by the heart team of physicians, mostly cardiologists and cardiac surgeons, to use these approaches. For the individual patient, the overall balance of risks, which cannot be determined by incision length only but rather should prioritize hard endpoints such as mortality and morbidity such as stroke are extremely important. Thus, an objective pre-procedural informative discussion individualized to each patient’s unique risks and potential outcomes is mandatory before choosing between open versus percutaneous options. In this perspective, we highlight the different aspects of choosing the TF versus the TA approach using the best available current literature and propose future prospects for the care of aortic valve disease.