Identifying drug-target interactions based on graph convolutional network and deep neural network.

Identification of new drug-target interactions (DTIs) is an important but a time-consuming and costly step in drug discovery. In recent years, to mitigate these drawbacks, researchers have sought to identify DTIs using computational approaches. However, most existing methods construct drug networks and target networks separately, and then predict novel DTIs based on known associations between the drugs and targets without accounting for associations between drug-protein pairs (DPPs). To incorporate the associations between DPPs into DTI modeling, we built a DPP network based on multiple drugs and proteins in which DPPs are the nodes and the associations between DPPs are the edges of the network. We then propose a novel learning-based framework, 'graph convolutional network (GCN)-DTI', for DTI identification. The model first uses a graph convolutional network to learn the features for each DPP. Second, using the feature representation as an input, it uses a deep neural network to predict the final label. The results of our analysis show that the proposed framework outperforms some state-of-the-art approaches by a large margin.

Use of Administrative Claims to Assess Outcomes and Treatment Effect in Randomized Clinical Trials for Transcatheter Aortic Valve Replacement: Findings From the EXTEND Study.

BACKGROUND: Whether passively collected data can substitute for adjudicated outcomes to reproduce the magnitude and direction of treatment effect observed in cardiovascular clinical trials is not well known. METHODS: We linked adults ≥65 years of age in the HiR (US CoreValve Pivotal High Risk) and SURTAVI trials (Surgical or Transcatheter Aortic Valve Replacement in Intermediate-Risk Patients) to 100% Medicare inpatient claims, January 1, 2011, to December 31, 2016. Primary (eg, death and stroke) and secondary trial end points were compared across treatment arms (eg, transcatheter aortic valve replacement [TAVR] versus surgical aortic valve replacement [SAVR]) using trial-adjudicated outcomes versus outcomes derived from claims at 1 year (HiR) or 2 years (SURTAVI). RESULTS: Among 600 linked HiR participants (linkage rate, 80.0%), the rate of the trial's primary end point of all-cause mortality occurred in 13.7% of patients receiving TAVR and 16.4% of patients receiving SAVR at 1 year by using both trial data (hazard ratio, 0.84 [95% CI, 0.65-1.09]; P=0.33) and claims data (hazard ratio, 0.86 [95% CI, 0.66-1.11]; P=0.34; interaction P value=0.80). Noninferiority of TAVR relative to SAVR was seen by using both trial- and claims-based outcomes (Pnoninferiority<0.001 for both). Among 1005 linked SURTAVI trial participants (linkage rate, 60.5%), the trial's primary end point was 12.9% for TAVR and 13.1% for SAVR using trial data (hazard ratio, 1.08 [95% CI, 0.79-1.48]; P=0.90), and 11.3% for TAVR and 12.5% for SAVR patients using claims data (hazard ratio, 1.02 [95% CI, 0.73-1.41]; P=0.58; interaction P value=0.89). TAVR was noninferior to SAVR when compared using both trial and claims (Pnoninferiority<0.001 for both). Rates of procedural secondary outcomes (eg, aortic valve reintervention, pacemaker rates) were more closely concordant between trial and claims data than nonprocedural outcomes (eg, stroke, bleeding, cardiogenic shock). CONCLUSIONS: In the HiR and SURTAVI trials, ascertainment of trial primary end points using claims reproduced both the magnitude and direction of treatment effect in comparison with adjudicated event data, but nonfatal and nonprocedural secondary outcomes were not as well reproduced. Use of claims to substitute for adjudicated outcomes in traditional trial treatment comparisons may be valid and feasible for all-cause mortality and certain procedural outcomes but may be less suitable for other end points.

Frailty and related outcomes in patients undergoing transcatheter valve therapies in a nationwide cohort.

AIMS: We sought to identify the prevalence and related outcomes of frail individuals undergoing transcatheter mitral valve repair and transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Patients aged 65 and older were included in the study if they had at least one procedural code for transcatheter mitral valve repair or TAVR between 1 January 2016 and 31 December 2016 in the Centers for Medicare and Medicaid Services Medicare Provider and Review database. The Hospital Frailty Risk Score, an International Classification of Diseases, Tenth Revision (ICD-10) claims-based score, was used to identify frailty and the primary outcome was all-cause 1-year mortality. A total of 3746 (11.6%) patients underwent transcatheter mitral valve repair and 28 531 (88.4%) underwent TAVR. In the transcatheter mitral valve repair and TAVR populations, respectively, there were 1903 (50.8%) and 14 938 (52.4%) patients defined as low risk for frailty (score <5), 1476 (39.4%) and 11 268 (39.5%) defined as intermediate risk (score 5-15), and 367 (9.8%) and 2325 (8.1%) defined as high risk (score >15). One-year mortality was 12.8% in low-risk patients, 29.7% in intermediate-risk patients, and 40.9% in high-risk patients undergoing transcatheter mitral valve repair (log rank P < 0.001). In patients undergoing TAVR, 1-year mortality rates were 7.6% in low-risk patients, 17.6% in intermediate-risk patients, and 30.1% in high-risk patients (log rank P < 0.001). CONCLUSIONS: This study successfully identified individuals at greater risk of short- and long-term mortality after undergoing transcatheter valve therapies in an elderly population in the USA using the ICD-10 claims-based Hospital Frailty Risk Score.

Validating the use of registries and claims data to support randomized trials: Rationale and design of the Extending Trial-Based Evaluations of Medical Therapies Using Novel Sources of Data (EXTEND) Study.

BACKGROUND: Randomized controlled trials are the "gold standard" for comparing the safety and efficacy of therapies but may be limited due to high costs, lack of feasibility, and difficulty enrolling "real-world" patient populations. The Extending Trial-Based Evaluations of Medical Therapies Using Novel Sources of Data (EXTEND) Study seeks to evaluate whether data collected within procedural registries and claims databases can reproduce trial results by substituting surrogate non-trial-based variables for exposures and outcomes. METHODS AND RESULTS: Patient-level data from 2 clinical trial programs-the Dual Antiplatelet Therapy Study and the United States CoreValve Studies-will be linked to a combination of national registry, administrative claims, and health system data. The concordance between baseline and outcomes data collected within nontrial data sets and trial information, including adjudicated end point events, will be assessed. We will compare the study results obtained using these alternative data sources to those derived using trial-ascertained variables and end points using trial-adjudicated end points and covariates. CONCLUSIONS: Linkage of trials to registries and claims data represents an opportunity to use alternative data sources in place of and as adjuncts to randomized clinical trial data but requires further validation. The results of this research will help determine how these data sources can be used to improve our present and future understanding of new medical treatments.

Readmissions After Revascularization Procedures for Peripheral Arterial Disease: A Nationwide Cohort Study.

Background: Limited data suggest high rates of unplanned rehospitalization after endovascular and surgical revascularization for peripheral arterial disease. However, the overall burden of readmissions has not been comprehensively explored. Objective: To evaluate nationwide readmissions after peripheral arterial revascularization for peripheral arterial disease and to assess whether readmission risk varies among hospitals. Design: Retrospective cohort study. Setting: 1085 U.S. acute care hospitals participating in the Nationwide Readmissions Database. Patients: 61 969 unweighted hospitalizations of patients with peripheral arterial disease who had peripheral arterial revascularization and were discharged alive between 1 January and 30 November 2014. Measurements: 30-day readmission rates, causes, and costs of unplanned rehospitalizations after peripheral arterial revascularization; 30-day risk-standardized readmission rates (RSRRs), calculated using hierarchical logistic regression, to assess for heterogeneity of readmission risk between hospitals. Results: Among 61 969 hospitalizations of patients with peripheral arterial disease who were discharged alive after peripheral arterial revascularization, the 30-day nonelective readmission rate was 17.6%. The most common cause of readmission was procedural complications (28.0%), followed by sepsis (8.3%) and complications due to diabetes mellitus (7.5%). Among rehospitalized patients, 21.0% underwent a subsequent peripheral arterial revascularization or lower extremity amputation, 4.6% died, and the median cost of a readmission was $11 013. Thirty-day RSRRs varied from 10.0% to 27.3% (interquartile range, 16.6% to 18.8%). Limitation: Inability to distinguish out-of-hospital deaths after discharge and potential misclassification bias due to use of billing codes to ascertain diagnoses and interventions. Conclusion: More than 1 in 6 patients with peripheral arterial disease who undergo peripheral arterial revascularization have unplanned readmission within 30 days, with high associated mortality risks and costs. Procedure- and patient-related factors were the primary reasons for readmission. Readmission rates varied moderately between institutions after hospital case mix was accounted for, suggesting that differences in hospital quality may only partially account for readmission. Primary Funding Source: Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center.

Applicability of Publicly Reported Hospital Readmission Measures to Unreported Conditions and Other Patient Populations: A Cross-sectional All-Payer Study.

Background: Readmission rates after hospitalizations for heart failure (HF), acute myocardial infarction (AMI), and pneumonia among Medicare beneficiaries are used to assess quality and determine reimbursement. Whether these measures reflect readmission rates for other conditions or insurance groups is unknown. Objective: To investigate whether hospital-level 30-day readmission measures for publicly reported conditions (HF, AMI, and pneumonia) among Medicare patients reflect those for Medicare patients hospitalized for unreported conditions or non-Medicare patients hospitalized with HF, AMI, or pneumonia. Design: Cross-sectional. Setting: Population-based. Participants: Hospitals in the all-payer Nationwide Readmissions Database in 2013 and 2014. Measurements: Hospital-level 30-day all-cause risk-standardized excess readmission ratios (ERRs) were compared for 3 groups of patients: Medicare beneficiaries admitted for HF, AMI, or pneumonia (Medicare reported group); Medicare beneficiaries admitted for other conditions (Medicare unreported group); and non-Medicare beneficiaries admitted for HF, AMI, or pneumonia (non-Medicare group). Results: Within-hospital differences in ERRs varied widely among groups. Medicare reported ratios differed from Medicare unreported ratios by more than 0.1 for 29% of hospitals and from non-Medicare ratios by more than 0.1 for 46% of hospitals. Among hospitals with higher readmission ratios, ERRs for the Medicare reported group tended to overestimate ERRs for the non-Medicare group but underestimate those for the Medicare unreported group. Limitation: Medicare groups and risk adjustment differed slightly from those used by the Centers for Medicare & Medicaid Services. Conclusion: Hospital ERRs, as estimated by Medicare to determine financial penalties, have poor agreement with corresponding measures for populations and conditions not tied to financial penalties. Current publicly reported measures may not be good surrogates for overall hospital quality related to 30-day readmissions. Primary Funding Source: Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology.

Rationale and Design of the SAFE-PAD Study.

BACKGROUND: Recent evidence from randomized controlled trials has raised concerns about the long-term safety of paclitaxel-coated peripheral devices used for femoropopliteal artery revascularization. In response to a call for more real-world data on the safety of these devices, the SAFE-PAD study (Safety Assessment of Femoropopliteal Endovascular treatment with Paclitaxel-coated Devices) was designed with input from the Food and Drug Administration to provide a long-term, comprehensive evaluation of the mortality risk associated with paclitaxel-coated devices among Medicare beneficiaries. METHODS AND RESULTS: SAFE-PAD is an observational cohort study of fee-for-service Medicare beneficiaries that underwent femoropopliteal artery revascularization with either a drug-coated device or nondrug-coated device from 2015 through 2018. All patients age 66 years or older who underwent revascularization will be identified using a combination of International Classification of Diseases, Tenth Revision procedural codes, Current Procedural Terminology codes, and Healthcare Common Procedure Coding System C-codes. The safety end point of all-cause death will be updated semiannually and continued until the median duration of follow-up surpasses 5 years. Sub-group analyses will be conducted by device type, patient characteristics, and procedural setting. Registration: The SAFE-PAD study has been registered on URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496544. CONCLUSIONS: The SAFE-PAD study will evaluate the long-term safety of drug-coated devices compared with nondrug-coated devices for femoropopliteal artery revascularization among a broad, real-world population of patients with peripheral artery disease.

Long-term outcomes of percutaneous coronary intervention for in-stent restenosis among Medicare beneficiaries.

BACKGROUND: In-stent restenosis (ISR) is highly prevalent and leads to repeat revascularisation. Long-term implications of ISR are poorly understood. AIMS: This study aimed to evaluate the long-term outcomes of patients undergoing percutaneous coronary intervention (PCI) for ISR. METHODS: National Cardiovascular Data Registry CathPCI records for individuals aged ≥65 years undergoing PCI from July 2009 to December 2014 were linked to Medicare claims. Baseline characteristics and long-term rates of death, myocardial infarction (MI), repeat revascularisation including target vessel revascularisation (TVR), and major adverse cardiovascular and cerebrovascular events (MACCE) were compared between ISR PCI versus de novo lesion PCI. RESULTS: Of 653,304 individuals, 10.2% underwent ISR PCI and 89.8% underwent de novo lesion PCI. The median duration of follow-up was 825 days (quartile 1: 352 days-quartile 3: 1,379 days). The frequency of MACCE (55.6% vs 45.0%; p<0.001), all-cause mortality (27.8% vs 25.5%; p<0.001), MI (19.0% vs 12.3%; p<0.001), repeat revascularisation (31.9% vs 18.6%; p<0.001), TVR (22.4% vs 8.0%; p<0.001), and stroke (8.8% vs 8.3%; p=0.005) was higher after ISR PCI. After multivariable adjustment, ISR PCI remained associated with worse long-term outcomes than after de novo lesion PCI (hazard ratio [HR] for MACCE 1.24 [95% CI: 1.22, 1.26], mortality 1.07 [95% CI: 1.05, 1.09], MI 1.44 [95% CI: 1.40, 1.48], repeat revascularisation 1.55 [95% CI: 1.51, 1.59], and TVR 2.50 [95% CI: 2.42, 2.58]). CONCLUSIONS: ISR PCI was common and was associated with a significantly higher risk of recurrent long-term major ischaemic events compared to patients undergoing de novo lesion PCI. There remains a need for new strategies to minimise ISR.

Relation of the Number of Cardiovascular Conditions and Short-term Symptom Improvement After Percutaneous Coronary Intervention for Stable Angina Pectoris.

With aging of the population, cardiovascular conditions (CC) are increasingly common in individuals undergoing PCI for stable angina pectoris (AP). It is unknown if the overall burden of CCs associates with diminished symptom improvement after PCI for stable AP. We prospectively administered validated surveys assessing AP, dyspnea, and depression to patients undergoing PCI for stable AP at our institution, 2016-2018. The association of CC burden and symptoms at 30-days post-PCI was assessed via linear mixed effects models. Included individuals (N = 121; mean age 68 ± 10 years; response rate = 42%) were similar to non-included individuals. At baseline, greater CC burden was associated with worse dyspnea, depression, and physical limitations due to AP, but not AP frequency or quality of life. PCI was associated with small improvements in AP and dyspnea (p ≤ 0.001 for both), but not depression (p = 0.15). After multivariable adjustment, including for baseline symptoms, CC burden was associated with a greater improvement in AP physical limitations (p = 0.01) and depression (p = 0.002), albeit small, but not other symptom domains (all p ≥ 0.05). In patients undergoing PCI for stable AP, increasing CC burden was associated with worse dyspnea, depression, and AP physical limitations at baseline. An increasing number of CCs was associated with greater improvements, though small, in AP physical limitations and depression. In conclusion, the overall number of cardiovascular conditions should not be used to exclude patients from PCI for stable AP on the basis of an expectation of less symptom improvement.

Relation of Frailty to Outcomes After Catheter Ablation of Atrial Fibrillation.

Catheter ablation for atrial fibrillation (AF) improves outcomes compared with medical treatment alone. Risk stratification for outcomes following AF ablation remains an important area of uncertainty. This analysis evaluated the association between frailty and outcomes following AF ablation. We evaluated US inpatients receiving AF ablation between January 1, 2016 and December 1, 2016 using Medicare fee-for-service billing codes. Diagnosis codes were used to calculate patients' Hospital Frailty Risk Score, with the cohort divided according to established cut-points of low (<5), intermediate (5 to 15), and high (>15) risk for frailty. The primary outcome was survival. Among 5,070 in patients treated with catheter ablation (mean age 74.9 ± 6.8 years, 51.1% female), 38.6% were defined as frail with a Hospital Frailty Risk Score >5, including 8.3% at high risk. Mortality rates (up to 630 days) were 5.8% in the low-risk group, 23.4% in the intermediate-risk group, and 42.2% in the high-risk group (log-rank p values <0.001 for comparison between categories). In restricted cubic spline regression analysis, the adjusted hazard ratios for long-term mortality monotonically increased with increasing values of the Hospital Frailty Risk Score (adjusted hazard ratio 1.065, 95% confidence interval 1.054 to 1.077). In secondary end points, frailty was independently associated with length of stay, postprocedure 30-day mortality, 30-day readmission and postdischarge 30-day mortality rates. In conclusion, frailty as assessed by a claims-based score is common in inpatient recipients of AF ablation, and provides risk stratification for mortality and other key clinical outcomes.

Association of Frailty With 30-Day Outcomes for Acute Myocardial Infarction, Heart Failure, and Pneumonia Among Elderly Adults.

Importance: The addition of a claims-based frailty metric to traditional comorbidity-based risk-adjustment models for acute myocardial infarction (AMI), heart failure (HF), and pneumonia improves the prediction of 30-day mortality and readmission. This may have important implications for hospitals that tend to care for frail populations and participate in Centers for Medicare & Medicaid Services value-based payment programs, which use these risk-adjusted metrics to determine reimbursement. Objective: To determine whether the addition of frailty measures to traditional comorbidity-based risk-adjustment models improved prediction of outcomes for patients with AMI, HF, and pneumonia. Design, Setting, and Participants: A nationwide cohort study included Medicare fee-for-service beneficiaries 65 years and older in the United States between January 1 and December 1, 2016. Analysis began August 2018. Main Outcomes and Measures: Rates of mortality within 30 days of admission and 30 days of discharge, as well as 30-day readmission rates by frailty group. We evaluated the incremental effect of adding the Hospital Frailty Risk Score (HFRS) to current comorbidity-based risk-adjustment models for 30-day outcomes across all conditions. Results: For 785 127 participants, there were 166 200 hospitalizations [21.2%] for AMI, 348 619 [44.4%] for HF, and 270 308 [34.4%] for pneumonia. The mean (SD) age at the time of hospitalization was 79.2 (8.9) years; 656 315 (83.6%) were white and 402 639 (51.3%) were women. The mean (SD) HFRS was 7.3 (7.4) for patients with AMI, 10.8 (8.3) for patients with HF, and 8.2 (5.7) for patients with pneumonia. Among patients hospitalized for AMI, an HFRS more than 15 (compared with an HFRS <5) was associated with a higher risk of 30-day postadmission mortality (adjusted odds ratio [aOR], 3.6; 95% CI, 3.4-3.8), 30-day postdischarge mortality (aOR, 4.0; 95% CI, 3.7-4.3), and 30-day readmission (aOR, 3.0; 95% CI, 2.9-3.1) after multivariable adjustment for age, sex, race, and comorbidities. Similar patterns were observed for patients hospitalized with HF (30-day postadmission mortality: aOR, 3.5; 95% CI, 3.4-3.7; 30-day postdischarge mortality: aOR, 3.5; 95% CI, 3.3-3.6; and 30-day readmission: aOR, 2.9; 95% CI, 2.8-3.0) and among patients with pneumonia (30-day postadmission mortality: aOR, 2.5; 95% CI, 2.3-2.6; 30-day postdischarge mortality: aOR, 3.0; 95% CI, 2.9-3.2; and 30-day readmission: aOR, 2.8; 95% CI, 2.7-2.9). The addition of HFRS to traditional comorbidity-based risk-prediction models improved discrimination to predict outcomes for all 3 conditions. Conclusions and Relevance: Among Medicare fee-for-service beneficiaries, frailty as measured by the HFRS was associated with mortality and readmissions among patients hospitalized for AMI, HF, or pneumonia. The addition of HFRS to traditional comorbidity-based risk-prediction models improved the prediction of outcomes for all 3 conditions.

Cost-effectiveness analysis of short-duration dual antiplatelet therapy with newer drug-eluting stent platforms versus longer-duration dual antiplatelet therapy with a second-generation drug-eluting stent in elective percutaneous coronary intervention.

BACKGROUND: The cost-effectiveness of newer drug-eluting stents (DES) such as biodegradable-polymer or polymer-free stents with shorter dual antiplatelet therapy (DAPT) duration is unknown. We evaluated the cost-effectiveness of treatment with newer DES that may allow for shorter DAPT duration. PATIENTS AND METHODS: We performed a cost-effectiveness analysis of treatment with newer DES platforms followed by 1 or 3 months of DAPT compared with standard second-generation DES followed by 6 or 12 months of DAPT in patients with stable coronary disease. A Markov model simulated distinct health states over a lifetime. Probabilistic sensitivity analysis and one-way sensitivity analyses were performed. A high-risk bleeding scenario was also evaluated. RESULTS: Among patients with typical bleeding risk, second-generation DES and 6 months of DAPT was less expensive and resulted in marginally higher quality-adjusted life years compared with other strategies. A newer DES platform and 3 months of DAPT was preferred when the risk of fatal bleeding was two times greater than baseline, or when bleeding increased long-term mortality by a factor of 1.5. In a probabilistic sensitivity analysis, second-generation DES and 6 months of DAPT was preferred in 58% of iterations, whereas in a high-risk bleeding patient scenario, a newer DES and 3 months of DAPT was preferred in 52% of iterations. CONCLUSION: A DES that allows 3 months of DAPT without increasing stent-related events is likely to be cost-effective among patients at elevated risk of bleeding, but not in patients with average bleeding risk.

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.

Association of Hospital Surgical Aortic Valve Replacement Quality With 30-Day and 1-Year Mortality After Transcatheter Aortic Valve Replacement.

Importance: Hospital outcomes for transcatheter aortic valve replacement (TAVR) may be dependent on the quality of evaluation, personnel, and procedural and postprocedural care common to patients undergoing cardiac surgery. Objectives: We sought to assess whether those hospitals with better patient outcomes for surgical aortic valve replacement (SAVR) subsequently achieved better TAVR outcomes after launching TAVR programs. Design, Setting, and Participants: This national cohort included US patients 65 years and older. The analysis used the Centers for Medicare and Medicaid Services' Medicare Provider and Review data collected between January 1, 2010, and September 29, 2015. Only hospitals performing at least 1 SAVR prior to September 1, 2011, and performing at least 1 TAVR after this date were included in the analysis. Data analysis was completed from June 2018 to August 2018. Interventions: Isolated aortic valve replacements. Main Outcomes and Measures: Hospital risk-adjusted 30-day mortality for SAVR in the pre-TAVR period was used as a surrogate for SAVR quality. Thirty-day and 1-year TAVR mortality rates were examined after stratification by quartile of baseline hospital risk-adjusted SAVR mortality. Results: A total of 51 924 TAVR procedures were performed in 519 hospitals, of which 19 798 were performed at hospitals in quartile 1 (the lowest risk-adjusted SAVR mortality rate), 7663 were performed in quartile 2, 10 180 were performed in quartile 3, and 14 283 were performed in quartile 4 (the highest risk-adjusted SAVR mortality rate). Observed mortality rates at 30 days consistently increased with increasing baseline hospital SAVR risk-adjusted mortality (quartile 1, 917 patients [4.6%]; quartile 2, 381 [5.0%]; quartile 3, 521 [5.1%]; quartile 4, 800 [5.6%]; P < .001). The same pattern was observed in 1-year mortality (quartile 1, 3359 [17.0%]; quartile 2, 1337 [17.5%]; quartile 3, 1852 [18.2%]; quartile 4, 2652 [18.6%]; P < .001). After multivariable analysis, compared with the lowest quartile of SAVR mortality, undergoing TAVR at a hospital with higher baseline SAVR mortality continued to be associated with higher 30-day mortality (odds ratios: quartile 2, 1.02 [95% CI, 0.87-1.21]; quartile 3, 1.13 [95% CI, 1.02-1.26]; quartile 4, 1.23 [95% CI, 1.07-1.40]; P = .02) and 1-year mortality (hazard ratios: quartile 2, 1.04 [95% CI, 0.92-1.17]; quartile 3, 1.14 [95% CI, 1.02-1.28]; quartile 4, 1.16 [95% CI, 1.05-1.28]; P = .02). Conclusions and Relevance: Hospitals with higher SAVR mortality rates also had higher short-term and long-term TAVR mortality after initiating TAVR programs. Quality of cardiac surgical care may be associated with a hospital's performance with new structural heart disease programs.

Depression and Angina Among Patients Undergoing Chronic Total Occlusion Percutaneous Coronary Intervention: The OPEN-CTO Registry.

OBJECTIVES: This study sought to examine depression prevalence among chronic total occlusion (CTO) patients and compared symptom improvement among depressed and nondepressed patients after percutaneous coronary intervention (PCI). BACKGROUND: Depression in cardiovascular patients is common, but its prevalence among CTO patients and its association with PCI response is understudied. METHODS: Among 811 patients from the OPEN-CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures) registry, we evaluated change in health status between baseline and 1-year post-PCI, as measured by the Seattle Angina Questionnaire (SAQ) and the Rose Dyspnea Score. Depression was defined using the Personal Health Questionnaire-8. The independent association between health status and depression following PCI was assessed using multivariable regression. RESULTS: Among the 811 patients, 190 (23%) screened positive for major depression, of whom 6.3% were on antidepressant therapy at intervention. Depressed patients experienced more baseline angina, but by 1-year post-PCI they experienced greater improvements than nondepressed patients (change in SAQ Summary: 31.4 ± 22.4 vs. 24.2 ± 20.0; p < 0.001). After adjustment, baseline depressed patients had more improvement in health status (adjusted difference in SAQ Summary improvement, depressed vs. nondepressed: 5.48 ± 1.81; p = 0.003). CONCLUSIONS: Depression is common among CTO PCI patients, but few were treated with antidepressants at baseline. Depressed patients had more severe baseline angina and significant improvement in health status after PCI. (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion [OPEN-CTO]; NCT02026466).

The Value of Claims-Based Nontraditional Risk Factors in Predicting Long-term Mortality After MitraClip Procedure.

BACKGROUND: We sought to identify nontraditional risk factors coded in administrative claims data and evaluate their ability to improve prediction of long-term mortality in patients undergoing percutaneous mitral valve repair. METHODS: Patients undergoing transcatheter mitral valve repair using MitraClip implantation between September 28, 2010, and September 30, 2015 were identified among Medicare fee-for-service beneficiaries. We used nested Cox regression models to identify claims codes predictive of long-term mortality. Four groups of variables were introduced sequentially: cardiac and noncardiac risk factors, presentation characteristics, and nontraditional risk factors. RESULTS: A total of 3782 patients from 280 clinical sites received treatment with MitraClip over the study period. During the follow-up period, 1114 (29.5%) patients died with a median follow-up time period of 13.6 (9.6 to 17.3) months. The discrimination of a model to predict long-term mortality including only cardiac risk factors was 0.58 (0.55 to 0.60). Model discrimination improved with the addition of noncardiac risk factors (c = 0.63, 0.61 to 0.65; integrated discrimination improvement [IDI] = 0.038, P < 0.001), and with the subsequent addition of presentation characteristics (c = 0.67, 0.65 to 0.69; IDI = 0.033, P < 0.001 compared with the second model). Finally, the addition of nontraditional risk factors significantly improved model discrimination (c = 0.70, 0.68 to 0.72; IDI = 0.019, P < 0.001, compared with the third model). CONCLUSIONS: Risk-prediction models, which include nontraditional risk factors as identified in claims data, can be used to predict long-term mortality risk more accurately in patients who have undergone MitraClip procedures.

Trends in Isolated Surgical Aortic Valve Replacement According to Hospital-Based Transcatheter Aortic Valve Replacement Volumes.

OBJECTIVES: This study sought to evaluate the trends in isolated surgical aortic valve replacement (SAVR) procedures across hospitals with different transcatheter aortic valve replacement (TAVR) volumes among Medicare beneficiaries. BACKGROUND: The volume of TAVR has increased in the United States since its approval, now exceeding that of isolated SAVR. METHODS: Hospitalizations of adults (≥18 years of age) with International Classification of Diseases-9th Revision-Clinical Modification procedure codes for SAVR (35.21 or 35.22) or TAVR (35.05 or 35.06) who were included in the Medicare Provider Analysis and Review database between January 1, 2011, and December 31, 2014, were included. Trends in isolated SAVR patient characteristics, procedural volumes, and outcomes by quartile (Q) of hospital-level TAVR use were assessed over the study period. RESULTS: A total of 37,705 isolated SAVR procedures were analyzed for the study. The annual volume of isolated SAVR procedures decreased in hospitals performing the largest number of TAVR procedures (Q3: 1,557 in 2011 to 1,391 in 2014; and Q4: 2,607 in 2011 to 1,791 in 2014). Thirty-day and 1-year mortality after SAVR also declined over the study period in hospitals with the largest TAVR volume (annual change rate in mortality for Q3: -16.4%; p < 0.001; Q4: -20.8%; p < 0.001). CONCLUSIONS: The advent of TAVR was associated with a reduction in isolated SAVR volumes, a decrease in comorbidities among patients undergoing SAVR, and corresponding reductions in observed short- and long-term SAVR mortality among hospitals performing the greatest number of TAVRs.

Meta-Analysis of Bleeding Risk Prediction Scores in Patients After Percutaneous Coronary Intervention on Dual Antiplatelet Therapy.

The duration and type of dual antiplatelet therapy (DAPT) prescribed to patients after percutaneous coronary intervention (PCI) involves carefully balancing reduced ischemia and increased bleeding risk for individual patients. Whereas multiple bleeding risk scores exist, the performance of these models to predict long-term bleeding in the setting of DAPT across different settings and populations is unclear. Therefore, we performed a systematic review and meta-analysis to compare the performance of current bleeding risk prediction scores for predicting major long-term bleeding events in patients on DAPT post-PCI. Based on a search of MEDLINE (January 1, 1946 to March 3, 2017) and EMBASE (January 1, 1974 to March 3, 2017) for studies published in the English language, we identified 10 published studies of 11 risk unique risk prediction models across a wide variety of settings. Area under the receiver operating characteristic curve (AUC) was used to measure discrimination, when available. Our findings reveal that the prediction models created to date demonstrate only modest accuracy, with the reported AUCs ranging from 0.54 to 0.89; aggregated AUC 0.68 (95% confidence intervals 0.65 to 0.72). Although only 5 studies (50%) reported measures of calibration, the reported models were reasonably well calibrated. Only 3 models (33%) were externally validated. Meta-regression demonstrated lack of influence by age (p = 0.99) or length of follow up (p = 0.42). Sensitivity analysis did not significantly change the results. Novel prediction models are warranted to aid in maximizing the benefit of DAPT after PCI while minimizing harm.

Impact of a Claims-Based Frailty Indicator on the Prediction of Long-Term Mortality After Transcatheter Aortic Valve Replacement in Medicare Beneficiaries.

Background Prospectively collected frailty markers are associated with an incremental 1-year mortality risk after transcatheter aortic valve replacement (TAVR) compared with comorbidities alone. Whether information on frailty markers captured retrospectively in administrative billing data is similarly predictive of long-term mortality after TAVR is unknown. We sought to characterize the prognostic importance of frailty factors as identified in healthcare billing records in comparison to validated measures of frailty for the prediction of long-term mortality after TAVR. Methods and Results Adult patients undergoing TAVR between August 25, 2011, and September 29, 2015, were identified among Medicare fee-for-service beneficiaries. The Johns Hopkins Claims-based Frailty Indicator was used to identify frail patients. We used nested Cox regression models to identify claims-based predictors of mortality up to 4 years post-procedure. Four groups of variables, including cardiac risk factors, noncardiac risk factors, patient procedural risk factors, and nontraditional markers of frailty, were introduced sequentially, and their integrated discrimination improvement was assessed. A total of 52 338 TAVR patients from 558 clinical sites were identified, with a mean follow-up time period of 16 months. In total, 14 174 (27.1%) patients died within the study period. The mortality rate was 53.9% at 4 years post-TAVR. A total of 34 863 (66.6%) patients were defined as frail. The discrimination of each of the 4 models was 0.60 (95% CI, 0.59-60), 0.65 (95% CI, 0.64-0.65), 0.68 (95% CI, 0.67-0.68), and 0.70 (95% CI, 0.69-0.70), respectively. The addition of nontraditional frailty markers as identified in claims improved mortality prediction above and beyond traditional risk factors (integrated discrimination improvement: 0.019; P<0.001). Conclusions Risk prediction models that include frailty as identified in claims data can be used to predict long-term mortality risk after TAVR. Linkage to claims data may allow enhanced mortality risk prediction for studies that do not collect information on frailty.