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Background: The ISCHEMIA trial found that patients with chronic coronary disease randomized to invasive strategy had better health status than those randomized to conservative strategy. It is unclear how best to translate these population-level results to individual patients., Objectives: The authors sought to identify patient characteristics associated with health status from invasive and conservative strategies, and develop a prediction algorithm for shared decision-making., Methods: One-year disease-specific health status was assessed in ISCHEMIA with the Seattle Angina Questionnaire (SAQ) Summary Score (SAQ SS) and Angina Frequency, Physical Limitations (PL), and Quality of Life (QL) domains (range 0-100, higher = less angina/better health status)., Results: Among 4,617 patients from 320 sites in 37 countries, mean SAQ SS was 74.1 ± 18.9 at baseline and 85.7 ± 15.6 at 1 year. Lower baseline SAQ SS and younger age were associated with better 1-year health status with invasive strategy (P interaction = 0.009 and P interaction = 0.004, respectively). For the individual domains, there were significant treatment interactions for baseline SAQ score (Angina Frequency, PL), age (PL, QL), anterior ischemia (PL), and number of baseline antianginal medications (QL), with more benefit of invasive in patients with worse baseline health status, younger age, anterior ischemia, and on more antianginal medications. Parsimonious prediction models were developed for 1-year SAQ domains with invasive or conservative strategies to support shared decision-making., Conclusions: In the management of chronic coronary disease, individual patient characteristics are associated with 1-year health status, with younger age and poorer angina-related health status showing greater benefit from invasive management. This prediction algorithm can support the translation of the ISCHEMIA trial results to individual patients. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522)., Competing Interests: Funding Support and Author Disclosures The research reported in this paper was funded through grants from National Institutes of Health/National Heart, Lung, and Blood Institute grants U01HL105907, U01HL105462, U01HL105561, and U01HL105565, Arbor Pharmaceuticals, AstraZeneca Pharmaceuticals, and Clinical and Translational Science Awards from the National Center for Advancing Translational Sciences (11UL1 TR001445 and UL1 TR002243). Devices or medications were provided by Abbott Vascular, Medtronic, St Jude Medical, Volcano, Amgen, Arbor Pharmaceuticals, AstraZeneca Pharmaceuticals, Espero Pharmaceuticals, Merck Sharp & Dohme, Omron Healthcare, and Sunovion Pharmaceuticals. Contents of this paper are solely the responsibility of the authors and do not necessarily represent official views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the Department of Health and Human Services. Dr Cohen has received research grant support from Abbott, Boston Scientific, Edwards Lifesciences, Philips, CathWorks, Zoll Medical, and I-Rhythm; and has received consulting income from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Reynolds has received in-kind support for unrelated research from Abbott Vascular, Siemens, and BioTelemetry. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; has been a consultant to Abbott, Daiichi-Sankyo, Ablative Solutions, CorFlow, Apollo Therapeutics, Cardiomech, Gore, Robocath, Miracor, Vectorious, Abiomed, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, Cardiac Success, and HighLife; holds equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; and receives institutional research grants from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Spertus owns the copyright to the Seattle Angina Questionnaire; has received consulting income from Janssen, Bayer, AstraZeneca, Novartis, and Merck; serves on the cardiovascular scientific advisory board of United Healthcare; is on the board of directors for Blue Cross Blue Shield of Kansas City; and holds equity interest in Health Outcomes Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The impact of complete revascularization (CR) on angina-related health status (symptoms, function, quality of life) in chronic coronary disease (CCD) has not been well studied., Objectives: Among patients with CCD randomized to invasive (INV) vs conservative (CON) management in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), we compared the following: 1) the impact of anatomic and functional CR on health status compared with incomplete revascularization (ICR); and 2) the predicted impact of achieving CR in all INV patients compared with CON., Methods: Multivariable regression adjusting for patient characteristics was used to compare 12-month health status after independent core laboratory-defined CR vs ICR in INV patients who underwent revascularization. Propensity-weighted modeling was then performed to estimate the treatment effect had CR or ICR been achieved in all INV patients, compared with CON., Results: Anatomic and functional CR were achieved in 43.3% and 57.8% of 1,641 INV patients, respectively. Among revascularized patients, CR was associated with improved Seattle Angina Questionnaire Angina Frequency compared with ICR after adjustment for baseline differences. After modeling CR and ICR in all INV patients, patients with CR and ICR each had greater improvements in health status than CON, with better health status with CR than ICR. The projected benefits of CR were most pronounced in patients with baseline daily/weekly angina and not seen in those with no angina., Conclusions: Among patients with CCD in ISCHEMIA, health status improved more with CR compared with ICR or CON, particularly in those with frequent angina. Anatomic and functional CR provided comparable improvements in quality of life. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522)., Competing Interests: Funding Support and Author Disclosures This work was supported by National Institutes of Health grants U01HL105907, U01HL105462, U01HL105561, U01HL105565, and T32 HL079896. This project was supported in part by Clinical Translational Science Award Nos. 11UL1 TR001445 and UL1 TR002243 from the National Center for Advancing Translational Sciences and by grants from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Devices or medications were provided by Abbott Vascular (previously St Jude Medical, Inc), Medtronic Inc, Phillips (previously Volcano Corporation), and Omron Healthcare Inc; and medications were provided by Amgen Inc, Arbor Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals, LP, Espero Pharmaceuticals, Merck, Sharp and Dohme Corp, and Sunovion Pharmaceuticals. Dr Mavromatis has received grants from the National Heart, Lung, and Blood Institute (CV Inflammation Reduction Trial and GMCSF in PAD-3 Trial), CSL Behring, St Jude Medical, Medtronic, DalCor Pharmaceuticals, AstraZeneca, Novartis, and Regeneron; and is a member of the American College of Cardiology and Society of Cardiovascular Angiography and Interventions. Dr Ali has received institutional grant support from Abbott, Abiomed, Acist Medical, Boston Scientific, Cardiovascular Systems Inc, Medtronic Inc, National Institutes of Health, Opsens Medical, Philips, and Teleflex; has received consulting fees from AstraZeneca, Philips, and Shockwave; and has equity in Elucid, Spectrawave, Shockwave, and VitalConnect. Dr Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, and Abbott; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; his daughter is an employee at IQVIA; and his employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Bangalore has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grants and personal fees from Abbott Vascular; and has received personal fees from Biotronik, Pfizer, Amgen, and Reata outside of the submitted work. Dr Genereux has served as a consultant for, advisor for, and received speaker fees from Abbott Vascular, Abiomed, BioTrace Medical, and Medtronic; has served as a consultant for Boston Scientific, CARANX Medical, Cardiovascular System Inc (PI Eclipse Trial), GE Healthcare, iRhythm Technologies, Opsens, Siemens Teleflex, and 4C Medical (PI Feasibility study); has served as a consultant for, advisor for, proctor for, and received speaker fees and institutional research grant from Edwards Lifesciences (PI EARLY-TAVR trial, PI PROGRESS trial); has equity in and is a consultant for Pi-Cardia, Puzzle Medical, Saranas, and Soundbite Medical Inc; and has served as a consultant for and received speaker fees from Shockwave. Dr Goodman has received grants and personal fees from the National Heart, Lung, and Blood Institute, during the conduct of the study, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, CSL Behring/PERFUSE, Daiichi-Sankyo/American Regent/DCRI, Ferring, Novartis, and Regeneron/Sanofi; and has received personal fees from Esperion/C5, Boehringer Ingelheim/Eli Lilly, GlaxoSmithKline, HLS Therapeutics, Merck, Novo Nordisk, and Servier, outside of the submitted work. Drs Alexander and Chen have received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Boden has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grants from Abbvie, Amarin, and Amgen; and has received personal fees from Amgen, Cleveland Clinic Clinical Coordinating Center, and Janssen outside of the submitted work. Dr Reynolds has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received support from Abbott Vascular (donation of optical coherence tomography catheters for an unrelated research study) and Biotelemetry Inc (donation of telemetry monitors for an unrelated research study). Dr Maron has received grants from the the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Hochman is PI for the ISCHEMIA trial for which, in addition to support by the National Heart, Lung, and Blood Institute grant, devices and medications were provided by Medtronic, Inc, Abbott Vascular, Inc (formerly St Jude Medical, Inc), Royal Philips NV (formerly Volcano Corporation), Arbor Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals, LP, Merck Sharp and Dohme Corp, Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc, Espero BioPharma, and Amgen Inc; and financial donations were provided by Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Spertus has provided consultative services on patient-reported outcomes and evidence valuation to Alnylam, AstraZeneca, Bayer, Merck, Janssen, Bristol Myers Squibb, Edwards, Kineksia, 4DT Medical, Terumo, Imbria, and United Healthcare; holds research grants from Bristol Myers Squibb, Abbott Vascular, and Janssen; owns the copyright to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Peripheral Artery Questionnaire; and serves on the Board of Directors for Blue Cross Blue Shield of Kansas City. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The contents of this paper are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences, the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the Department of Health and Human Services., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown., Objectives: The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial., Methods: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure., Results: Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged ≥75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (P interaction  = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (P interaction  = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (P interaction  = 0.29)., Conclusions: Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522)., Competing Interests: Funding Support and Author Disclosures This project was supported in part by National Institutes of Health grants U01HL105907, U01HL105462, U01HL105561, and U01HL105565; and in part by Clinical Translational Science Award numbers 11UL1 TR001445 and UL1 TR002243 from the National Center for Advancing Translational Sciences. The contents of this project are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the Department of Health and Human Services. Dr Nguyen is currently supported by the National Heart, Lung, and Blood Institute under Award Number T32HL110837. Dr Spertus has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received personal fees from Bayer, Novartis, AstraZeneca, Amgen, Janssen, and United Healthcare; has received grants from the American College of Cardiology, outside the submitted work; has a patent copyright to SAQ with royalties paid; is on the Board of Directors for Blue Cross Blue Shield of Kansas City; and has equity in Health Outcomes Sciences. Dr Newman, Dr Alexander, Mrs Stevens, Dr O'Brien, Dr Gamma, Dr Perna, Dr Garg, Dr Vertes, Dr Smanio, Dr Senior, Dr Held, and Dr Maron have received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Mr Jones reports employment by the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research; receives research support from TD Bank, CV Diagnostix, AusculSciences, and Siemens Healthineers; and has equity interest in General Electric. Dr White has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grant support paid to the institution and fees for serving on a steering committee for the ODYSSEY OUTCOMES trial from Sanofi and Regeneron Pharmaceuticals, for the ACCELERATE study from Eli Lilly, for the STRENGTH trial from Omthera Pharmaceuticals, for the HEART-FID study from American Regent, for the CAMELLIA-TIMI study from Eisai Inc, for the dal-GenE study from DalCor Pharma UK Inc, for the AEGIS-II study from CSL Behring, for the SCORED trial and the SOLOIST-WHF trial from Sanofi Australia Pty Ltd, and for the CLEAR Outcomes Study from Esperion Therapeutics Inc. Dr White was on the Advisory Board for Genentech, Inc; and has received lecture fees from AstraZeneca. Dr Boden has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grants from AbbVie, Amarin, and Amgen; and has received personal fees from Amgen, the Cleveland Clinic Clinical Coordinating Center, and Janssen, outside the submitted work. Dr Mark has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received grants from HeartFlow and Merck, outside the submitted work. Dr Reynolds has received funding for this research from the National Heart, Lung, and Blood Institute; and has received in-kind donations for unrelated research from Abbott Vascular, Siemens, and Philips. Dr Bangalore has received grants from the National Heart, Lung, and Blood Institute and Abbott Vascular; and serves on the advisory board for Abbott Vascular, Pfizer, Amgen, Biotronik, Meril, and Reata. Dr Chan has received funding from the American Heart Association; and is a consultant for Optum Rx. Dr Stone has received grants and personal fees from the National Heart, Lung, and Blood Institute during the conduct of the study; has received personal fees from Terumo, Amaranth, Shockwave, TherOx, Reva, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Matrizyme, Miracor, Neovasc, V-Wave, Abiomed, Claret, Sirtex, MAIA Pharmaceuticals, and Vectorious; has received personal fees and has equity/options from VALFIX, Ancora, Qool Therapeutics, SpectraWave, and Orchestra Biomed; has equity/options from Cagent, Applied Therapeutics, BioStar family of funds, MedFocus family of funds, and Aria; and has equity/options from Cardiac Success, outside the submitted work. Dr Hochman is Principal Investigator for the ISCHEMIA trial for which, in addition to support by a National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular, Medtronic, Inc, Abbott Laboratories (formerly St Jude Medical, Inc), Royal Philips NV (formerly Volcano Corporation), Arbor Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals, LP, Merck Sharp & Dohme Corp, Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc, Espero BioPharma, and Amgen, Inc, as well as financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial randomized participants with chronic coronary disease (CCD) to guideline-directed medical therapy with or without angiography and revascularization. The study examined the association of nonadherence with health status outcomes., Objectives: The study sought to compare 12-month health status outcomes of adherent and nonadherent participants with CCD with an a priori hypothesis that nonadherent patients would have better health status if randomized to invasive management., Methods: Self-reported medication-taking behavior was assessed at randomization with a modified 4-item Morisky-Green-Levine Adherence Scale, and participants were classified as adherent or nonadherent. Twelve-month health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ-7) summary score (SS), which ranges from 0 to 100 (higher score = better). The association of adherence with outcomes was evaluated using Bayesian proportional odds models, including an interaction by study arm (conservative vs invasive)., Results: Among 4,480 randomized participants, 1,245 (27.8%) were nonadherent at baseline. Nonadherent participants had worse baseline SAQ-7 SS in both conservative (72.9 ± 19.3 vs 75.6 ± 18.4) and invasive (71.0 ± 19.8 vs 74.2 ± 18.7) arms. In adjusted analyses, adherence was associated with higher 12-month SAQ-7 SS in both treatment groups (mean difference in SAQ-7 SS with conservative treatment = 1.6 [95% credible interval: 0.3-2.9] vs with invasive management = 1.9 [95% credible interval: 0.8-3.1]), with no interaction by treatment., Conclusions: More than 1 in 4 participants reported medication nonadherence, which was associated with worse health status in both conservative and invasive treatment strategies at baseline and 12 months. Strategies to improve medication adherence are needed to improve health status outcomes in CCD, regardless of treatment strategy. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522)., Competing Interests: Funding Support and Author Disclosures Dr Garcia is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number 5T32H110837. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Spertus owns the copyright to the Kansas City Cardiomyopathy Questionnaire and Seattle Angina Questionnaire; unrelated to this work, he has served as a consultant on patient-reported outcomes for Janssen, Pfizer, Bristol Myers Squibb, Bayer, Merck, Novartis, Corvia, Terumo, and Abbott; has received research grants from the American College of Cardiology Foundation, Janssen, MyoKardia, and Abbott Vascular; has served on the scientific advisory board for United Healthcare; and has served on the Board of Directors of Blue Cross Blue Shield of Kansas City. Dr Newman has received funding from the National Heart, Lung, and Blood Institute. Dr Bangalore has served as a consultant to Abbott Vascular, Biotronik, Pfizer, and Amgen; and has received research grants from the National Heart, Lung, and Blood Institute and Abbott Vascular. Dr Stone has received speaker honoraria from Cook and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Reva, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, and Gore; and owns equity or options in Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and MedFocus family of funds. Dr. Reynolds has received funding from the National Heart, Lung, and Blood Institute; and has received in-kind donations for unrelated research from Abbott Vascular, Siemens, and BioTelemetry. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. All rights reserved.)

To improve the patient-centeredness of care, patient-reported outcomes have been increasingly used to quantify patients' symptoms, function, and quality of life. In heart failure, the Kansas City Cardiomyopathy Questionnaire (KCCQ) has been qualified by the U.S. Food and Drug Administration as a Clinical Outcome Assessment and recommended as a performance measure for quantifying the quality of care. By systematically asking the same questions reproducibly over time, the KCCQ can validly and sensitively capture the impact of heart failure on patients' lives and is strongly associated with clinical events over time. This review describes how to interpret the KCCQ, how it should be analyzed in clinical trials to maximize the interpretability of results, and how it can be used in clinical practice and population health. By providing a deeper understanding of the KCCQ, it is hoped that its use can further improve the patient-centeredness of heart failure care., Competing Interests: Author Relationship With Industry Dr. Spertus owns the copyright to the Kansas City Cardiomyopathy Questionnaire. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In patients with coronary artery disease (CAD), low diastolic blood pressure (DBP) is associated with increased risk of myocardial infarction, but its association with angina is unknown., Objectives: The goal of this study was to examine the association of low DBP and angina in patients with CAD., Methods: The study assessed the frequency of angina (measured by using the Seattle Angina Questionnaire-Angina Frequency score) according to DBP in patients with known CAD from 25 U.S. cardiology clinics. Hierarchical logistic regression was used to test the association between DBP and angina, with a spline term for DBP to assess nonlinearity., Results: Among 1,259 outpatients with CAD, 411 (33%) reported angina in the prior month, with higher rates in the lowest DBP quartile (40 to 64 mm Hg: 37%). In the unadjusted model, DBP was associated with angina with a J-shaped relationship (p = 0.017, p for nonlinearity = 0.027), with a progressive increase in odds of angina as DBP decreased below ∼70 to 80 mm Hg. This association remained significant after sequential adjustment for demographic characteristics (p = 0.002), comorbidities (p = 0.002), heart rate (p = 0.002), systolic blood pressure (p = 0.046), and antihypertensive antianginal medications (p = 0.045)., Conclusions: In patients with chronic CAD, there seemed to be an association between lower DBP and increased odds of angina. If validated, these findings suggest that clinicians should consider less aggressive blood pressure control in patients with CAD and angina., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A series of models have been developed to identify patients at high risk for poor outcomes after transcatheter aortic valve replacement (TAVR) to help guide treatment choices, offer patients realistic expectations of long-term outcomes, and support decision making., Objectives: This study examined the performance of the previously developed TAVR Poor Outcome risk models in an external dataset and explored the incremental contribution of geriatric domains to model performance., Methods: Poor outcome after TAVR was defined as death, poor quality of life (QOL), or decline in QOL, as assessed using the Kansas City Cardiomyopathy Questionnaire. We tested 4 TAVR Poor Outcome risk models: 6-month and 1-year full and clinical (reduced) models. We examined each model's discrimination and calibration in the CoreValve trial dataset, and then tested the incremental contribution of frailty and disability markers to the model's discrimination using the incremental discrimination index., Results: Among 2,830 patients who underwent TAVR in the CoreValve US Pivotal Extreme and High Risk trials and associated continued access registries, 31.2% experienced a poor outcome at 6 months following TAVR (death, 17.6%; very poor QOL, 11.6%; QOL decline, 2.0%) and 50.8% experienced a poor outcome at 1 year (death, 30.2%; poor QOL, 19.6%; QOL, decline 1.0%). The models demonstrated similar discrimination as in the Placement of Aortic Transcatheter Valves Trial cohorts (c-indexes, 0.637 to 0.665) and excellent calibration. Adding frailty as a syndrome increased the c-indexes by 0.000 to 0.004 (incremental discrimination index, p < 0.01 for all except the 1-year clinical model), with the most important individual components being disability and unintentional weight loss., Conclusions: Although discrimination of the TAVR Poor Outcome risk models was generally moderate, calibration was excellent among patients with different risk profiles and treated with a different TAVR device. These findings demonstrated the value of these models for individualizing outcome predictions in high-risk patients undergoing TAVR., Competing Interests: The other authors report no potential conflicts., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to examine the efficacy of ranolazine versus placebo on weekly angina frequency and sublingual nitroglycerin use in subjects with type 2 diabetes mellitus, coronary artery disease (CAD), and chronic stable angina who remain symptomatic despite treatment with up to 2 antianginal agents., Background: Patients with diabetes have more extensive CAD than those without diabetes, and a high burden of angina. Ranolazine is not only effective in treating angina but also may improve glycemic control, thus providing several potential benefits in this high-risk group. We conducted a randomized trial to test the antianginal benefit of ranolazine in patients with diabetes and stable angina., Methods: TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina) was an international, randomized, double-blind trial of ranolazine versus placebo in patients with diabetes, CAD, and stable angina treated with 1 to 2 antianginals. After a single-blind, 4-week placebo run-in, patients were randomized to 8 weeks of double-blind ranolazine (target dose 1000 mg bid) or placebo. Anginal episodes and nitroglycerin use were recorded with daily entry into a novel electronic diary. Primary outcome was the average weekly number of anginal episodes over the last 6 weeks of the study., Results: A total of 949 patients were randomized across 104 centers in 14 countries. Mean age was 64 years, 61% were men, mean diabetes duration was 7.5 years, and mean baseline HbA1c was 7.3%. Electronic diary data capture was 98% in both groups. Weekly angina frequency was significantly lower with ranolazine versus placebo (3.8 [95% confidence interval (CI): 3.6 to 4.1] episodes vs. 4.3 [95% CI: 4.0 to 4.5] episodes, p = 0.008), as was the weekly sublingual nitroglycerin use (1.7 [95% CI: 1.6 to 1.9] doses vs. 2.1 [95% CI: 1.9 to 2.3] doses, p = 0.003). There was no difference in the incidence of serious adverse events between groups., Conclusions: Among patients with diabetes and chronic angina despite treatment with up to 2 agents, ranolazine reduced angina and sublingual nitroglycerin use and was well tolerated. (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina [TERISA]; NCT01425359)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Overcoming racial differences in acute coronary syndrome (ACS) outcomes is a strategic goal for U.S. health care. Genetic polymorphisms in the adrenergic pathway seem to explain some outcome differences by race in other cardiovascular diseases treated with β-adrenergic receptor blockade (BB). Whether these genetic variants are associated with survival among ACS patients treated with BB, and if this differs by race, is unknown., Background: β-adrenergic receptor blockade after ACS is a measure of quality care, but the effectiveness across racial groups is less clear., Methods: A prospective cohort of 2,673 ACS patients (2,072 Caucasian; 601 African-American) discharged on BB from 22 U.S. hospitals were followed for 2 years. Subjects were genotyped for polymorphisms in ADRB1, ADRB2, ADRA2C, and GRK5. We used proportional hazards regression to model the effect of genotype on mortality, stratified by race and adjusted for baseline factors., Results: The overall 2-year mortality rate was 7.5% for Caucasians and 16.7% for African Americans. The prognosis associated with different genotypes in these BB-treated patients differed by race. In Caucasians, ADRA2C 322-325 deletion carriers had significantly lower mortality as compared with homozygous individuals lacking the deletion (hazard ratio: 0.46; confidence interval [CI]: 0.21 to 0.99; p = 0.047; race × genotype interaction p = 0.053). In African Americans, the ADRB2 16R allele was associated with significantly increased mortality (hazard ratio for RG vs. GG: 2.10; CI: 1.14 to 3.86; RR vs. GG: 2.65; CI: 1.38 to 5.08; p = 0.013; race × genotype interaction p = 0.096)., Conclusions: Adrenergic pathway polymorphisms are associated with mortality in ACS patients receiving BB in a race-specific manner. Understanding the mechanism by which different genes impact post-ACS mortality differently in Caucasians and African Americans might illuminate opportunities to improve BB therapy in these groups., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to compare the consistency in appropriate use criteria (AUC) ratings among a broad range of practicing cardiologists and the AUC Technical Panel., Background: AUC for coronary revascularization have been developed by selected experts., Methods: Before AUC publication, 85 cardiologists from 10 U.S. institutions assessed the appropriateness of coronary revascularization for 68 indications that had been evaluated by the AUC Technical Panel. Each indication was classified as appropriate, uncertain, or inappropriate, based on the physician group's median rating. Rates of concordance between the physician group and the AUC Technical Panel (i.e., same appropriateness category assignment) and rates of nonagreement within the physician group (≥ 25% of panelists' ratings outside the group's appropriateness category assessment) were determined., Results: Overall concordance between the 2 groups was 84%. Among indications classified as appropriate by the AUC Technical Panel, concordance between the 2 groups was excellent (94% [34 of 36]); however, nonagreement within the physician group was 44% (16 of 36). Among indications classified as uncertain, there was 73% (16 of 22) concordance between the 2 groups. Among inappropriate indications, concordance was moderate (70% [7 of 10]), but nonagreement occurred frequently (70% [7 of 10]). Moreover, there was substantial variation in appropriateness ratings between individual physicians and the AUC Technical Panel (weighted kappa range: 0.05 to 0.76)., Conclusions: Although there was good concordance in assessments of appropriateness for coronary revascularization between physicians and the AUC Technical Panel, nonagreement within the physician group was common and there was marked variation in ratings between individual physicians and the AUC Technical Panel., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We examined compliance with performance measures for 14,464 patients enrolled from July 2008 through June 2009 into the American College of Cardiology's PINNACLE (Practice Innovation And Clinical Excellence) program to provide initial insights into the quality of outpatient cardiac care., Background: Little is known about the quality of care of outpatients with coronary artery disease (CAD), heart failure, and atrial fibrillation, and whether sex and racial disparities exist in the treatment of outpatients., Methods: The PINNACLE program is the first, national, prospective office-based quality improvement program of cardiac patients designed, in part, to capture, report, and improve outpatient performance measure compliance. We examined the proportion of patients whose care was compliant with established American College of Cardiology, American Heart Association, and American Medical Association-Physician Consortium for Performance Improvement (ACC/AHA/PCPI) performance measures for CAD, heart failure, and atrial fibrillation., Results: There were 14,464 unique patients enrolled from 27 U.S. practices, accounting for 18,021 clinical visits. Of these, 8,132 (56.4%) had CAD, 5,012 (34.7%) had heart failure, and 2,786 (19.3%) had nonvalvular atrial fibrillation. Data from the PINNACLE program were feasibly collected for 24 of 25 ACC/AHA/PCPI performance measures. Compliance with performance measures ranged from being very low (e.g., 13.3% of CAD patients screened for diabetes mellitus) to very high (e.g., 96.7% of heart failure patients with blood pressure assessments), with moderate (70% to 90%) compliance observed for most performance measures. For 3 performance measures, there were small differences in compliance rates by race or sex., Conclusions: For more than 14,000 patients enrolled from 27 practices in the outpatient PINNACLE program, we found that compliance with performance measures was variable, even after accounting for exclusion criteria, suggesting an important opportunity to improve the quality of outpatient care., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We sought to define acute mortality in hospitalized patients undergoing clinically indicated echocardiography with and without use of an ultrasound contrast agent., Background: The U.S. Food and Drug Administration recently issued a boxed warning and new contraindications for the perflutren-containing ultrasound contrast agents following post-marketing reports of 4 patient deaths that were temporally related to Definity (Bristol-Myers Squibb Medical Imaging, Billerica, Massachusetts) administration. To appreciate the incremental risk of any medical procedure, the ambient risk of untoward outcome in the population in question must first be defined. There are no published data on short-term major adverse cardiac events in hospitalized patients undergoing echocardiography, either with or without administration of an ultrasound contrast agent., Methods: A retrospective analysis of hospitalized patients undergoing clinically indicated echocardiography between January 2005 and October 2007, within Saint Luke's Health System, Kansas City, Missouri, was performed. Studies were separated into 2 groups, those performed without contrast enhancement (n = 12,475) and those performed with Definity (n = 6,196). Vital status within 24 h of the echocardiographic study was available for all patients using a combination of the Social Security Death Master File and Saint Luke's Health System medical records. Incidence of death within 24 h was compared by chi-square test between Definity and unenhanced procedures., Results: Of the 18,671 patient events, 72 patients died within 24 h. Of those that underwent unenhanced echocardiography, 46 died within 24 h (0.37%). Of patients receiving Definity during the echocardiogram, 26 died within 24 h (0.42%). There was no statistical difference between these 2 groups (p = 0.60). No patient died within 1 h of the echocardiographic study. In a random sampling from the unenhanced (n = 201) and Definity groups (n = 202), patients who underwent Definity-enhanced echocardiography exhibited higher clinical acuity, and more significant comorbidities., Conclusions: Approximately 0.4% of hospitalized patients die within 24 h of echocardiography. There is no increased mortality risk associated with Definity-enhanced examinations, despite evidence for higher clinical acuity and more comorbid conditions in patients undergoing contrast studies.

Objectives: We tested the hypothesis that one health status measure, the Kansas City Cardiomyopathy Questionnaire (KCCQ), provides prognostic information independent of other clinical data in outpatients with heart failure (HF)., Background: Health status measures are used to describe a patient's clinical condition and have been shown to predict mortality in some populations. Their prognostic value may be particularly useful among patients with HF for identifying candidates for disease management in whom increased care may reduce hospitalizations and prevent death., Methods: We evaluated 505 HF patients from 13 outpatient clinics who had an ejection fraction <40% using the KCCQ summary score. Proportional hazards regression was used to evaluate the association between the KCCQ summary score (range, 0 to 100; higher scores indicate better health status) and the primary outcome of death or HF admission, adjusting for baseline patient characteristics, 6-min walk distance, and B-type natriuretic peptide (BNP)., Results: The mean age was 61 years, 76% of patients were male, 51% had an ischemic HF etiology, and 5% were New York Heart Association functional class IV. At 12 months, among the 9% of patients with a KCCQ score <25, 37% had been admitted for HF and 20% had died, compared with 7% (HF admissions) and 5% (death) of those with a KCCQ score > or =75 (33% of patients, p < 0.0001 for both comparisons). In sequential multivariable models adjusting for clinical variables, 6-min walk, and BNP levels, the KCCQ score remained significantly associated with survival free of HF hospitalization., Conclusions: A low KCCQ score is an independent predictor of poor prognosis in outpatients with HF.

Objectives: We sought to investigate the role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in preventing the new onset of type 2 diabetes mellitus., Background: Diabetes is a public health problem of epidemic proportions and its prevalence is on the rise. The typical American born today has a one in three chance of developing type 2 diabetes. This diagnosis is associated with an adverse cardiovascular prognosis and is considered the risk equivalent of established coronary disease. Even in high-risk individuals, diabetes is a preventable disease. Several studies have shown that ACE inhibitors and ARBs decrease the incidence of new-onset type 2 diabetes. However, the exact role of these agents in diabetes prevention has not yet been fully elucidated., Methods: We conducted a meta-analysis of 12 randomized controlled clinical trials of ACE inhibitors or ARBs, identified through a MEDLINE search and a review of reports from scientific meetings, to study the efficacy of these medications in diabetes prevention., Results: This showed that ACE inhibitors and ARBs were associated with reductions in the incidence of newly diagnosed diabetes by 27% and 23%, respectively, and by 25% in the pooled analysis., Conclusions: The use of an ACE inhibitor or ARB should be considered in patients with pre-diabetic conditions such as metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure, or coronary heart disease.

Objectives: The objective of this study was to identify the factors associated with the development of depressive symptoms in outpatients with heart failure (HF)., Background: Depression is common in patients with HF and has been linked to adverse outcomes., Methods: This was a multicenter prospective cohort study of outpatients with HF and ejection fraction <0.40. Patients were evaluated at baseline and one year with a Medical Outcomes Study-Depression questionnaire, a Kansas City Cardiomyopathy Questionnaire (KCCQ), and a full clinical evaluation including patients' social and economic status., Results: Of 245 patients without depressive symptoms at baseline, 52 (21.2%) developed depressive symptoms one year later. In multivariable analysis, living alone, alcohol abuse, perception of medical care as being a substantial economic burden, and health status as measured by the KCCQ were independent predictors of developing depressive symptoms. For patients without these factors, 7.9% developed depression by one year. When one factor was present, the one-year incidence was 15.5%, when two were present the incidence was 36.2%, and when three were present the incidence was 69.2%. There was a graded relationship between poorer health status and increased risk of developing depression (p < 0.001 for trend). No traditional clinical factors or measures of disease severity were significantly associated with the development of depression., Conclusions: Social factors and health status are predictive of the development of depression in outpatients with HF. Clinicians should be aware of which patients are at risk for the development of depression so that these patients may be targeted for screening and potentially for psychosocial intervention.