Comparison of Clinical Trials and Administrative Claims to Identify Stroke Among Patients Undergoing Aortic Valve Replacement: Findings From the EXTEND Study.

BACKGROUND: Cerebrovascular events (CVEs) are devastating complications after aortic valve replacement. We assessed whether billing claims accurately identify CVEs in place of clinical event adjudication in structural heart disease trials. METHODS: Adult participants in the US CoreValve High Risk and SURTAVI trials (Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients) were linked to Medicare inpatient claims from January 1, 2006 to December 31, 2016. Claims consistent with CVEs within 14 days of a similar trial-adjudicated CVE were considered a match. The sensitivity, specificity, and positive and negative predictive values of International Classification of Diseases,Ninth andTenthRevisions, Clinical Modification billing codes for cerebrovascular disease were determined against trial-defined CVEs as the criterion standard. Kaplan-Meier estimates of claims-defined versus trial-defined CVEs were compared. RESULTS: Among 4230 linked trial participants (linkage rate 79.8%), 550 (13.0%) sustained 630 adjudicated CVEs over a 5-year follow-up period. Linked and nonlinked individuals were similar. An algorithm using 4 International Classification of Diseases, Ninth Revision, Clinical Modification codes (434.91, 434.11, 433.11, and 997.02) had a sensitivity of 60.9%, specificity of 99.0%, positive predictive value of 86.5%, and negative predictive value of 95.8% for identifying a trial-adjudicated ischemic stroke. An algorithm using 3 International Classification of Diseases, Tenth Revision, Clinical Modification codes (I63.9, I63.40, I63.49) had a sensitivity of 66.7%, specificity of 99.4%, positive predictive value of 88.9%, and negative predictive value of 97.6%. CONCLUSIONS: In linked clinical trial and Medicare claims data, 4 International Classification of Diseases, Ninth Revision, Clinical Modification and 3 International Classification of Diseases, Tenth Revision, Clinical Modification billing codes identified half of trial-adjudicated CVEs during follow-up with high specificity and predictive value, but imperfect sensitivity. Although low sensitivity may limit the use of claims to substitute for traditional trial outcomes to identify CVEs, high specificity suggests claims could be used to trigger evaluation of neurological events, potentially improving the efficiency of the evaluation of techniques and devices designed to reduce such events.

Effect of Baseline Aortic Regurgitation on Mortality in Patients Treated With Transcatheter or Surgical Aortic Valve Replacement (from the CoreValve US Pivotal Trial).

This study was performed to determine if baseline aortic regurgitation (AR) affects the deleterious effects of postprocedure paravalvular leak following transcatheter aortic valve implantation (TAVI). We evaluated the effect of baseline AR on mortality in a large cohort of patients randomized to transcatheter or surgical aortic valve replacement (SAVR). The analysis cohort comprised 739 patients who underwent attempted TAVI (n = 386) or SAVR (n = 353) in the CoreValve US Pivotal High Risk Trial and had baseline AR measurements. Patients were stratified by the severity of baseline AR into those with none and/or trace and those with ≥mild AR. Echocardiographic measurements were assessed by an independent core laboratory. Of the 386 TAVI patients, 204 (52.9%) had none and/or trace at baseline AR; 182 (47.2%) had ≥mild AR. Of the 353 SAVR patients, 169 (47.9%) had none and/or trace and 184 (52.1%) ≥mild AR. The presence of ≥mild baseline AR was associated with lower all-cause mortality at 1 year following TAVI (9.4% vs 18.6%, p = 0.008) or SAVR (13.3% vs 24.4%, p = 0.009). Mortality remained lower in the ≥mild baseline AR patients at 3 years after SAVR (p = 0.011), but not TAVI. In conclusion, baseline AR appears to provide a protective effect on survival and quality of life in both TAVI and SAVR patients at 1 year; this effect persists out to 3 years in SAVR patients.

Regression of Paravalvular Aortic Regurgitation and Remodeling of Self-Expanding Transcatheter Aortic Valve: An Observation From the CoreValve U.S. Pivotal Trial.

OBJECTIVES: The aim of this study was to describe the natural history and clinical importance of paravalvular aortic regurgitation (PVAR) after CoreValve transcatheter aortic valve replacement (TAVR) and to relate these findings to the structural and hemodynamic changes documented by serial echocardiographic analysis. BACKGROUND: PVAR after TAVR with the self-expanding CoreValve bioprosthesis has been shown to regress over time, but the time course and the mechanism of PVAR regression has not been completely characterized. METHODS: Patients with severe aortic stenosis who underwent CoreValve TAVR and followed up to 1 year in the multicenter CoreValve U.S. Pivotal Trial (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement) were studied. Serial echocardiography studies were analyzed by an echocardiographic core laboratory. Annular sizing ratio was calculated from computed tomography measurements. Paired, as well as total, data were compared. RESULTS: The CoreValve was implanted in 634 patients with a mean age of 82.7 ± 8.4 years. After a marked improvement noted at discharge, aortic valve velocity, mean gradient, and effective orifice area further improved significantly at 1 month (2.08 ± 0.45 m/s vs. 1.99 ± 0.46 m/s, p < 0.0001, 9.7 ± 4.4 mm Hg vs. 8.9 ± 4.6 mm Hg, p < 0.0001, and 1.78 ± 0.51 cm(2) vs. 1.85 ± 0.58 cm(2), p = 0.03, respectively). The improvement was sustained through 1 year. PVAR was moderate or severe in 9.9%, and of 36 patients with moderate PVAR at discharge and paired data, 30 (83%) improved at least 1 grade of regurgitation at 1 year. Annular sizing ratio was significantly associated with the degree of PVAR. CONCLUSIONS: There was further improvement in aortic prosthetic valve hemodynamics and regression of PVAR up to 1 year compared with discharge after TAVR with CoreValve. These changes are possibly due to remodeling and outward expansion of the self-expandable CoreValve with nitinol frame. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement [Medtronic CoreValve U.S. Pivotal Trial]; NCT01240902).