Search

Background: Caregivers of patients with advanced heart failure may experience burden in providing care, but whether changes in patient health status are associated with caregiver burden is unknown., Methods: This observational study included older patients (60-80 years old) receiving advanced surgical heart failure therapies and their caregivers at 13 US sites. Patient health status was assessed using the 12-item Kansas City Cardiomyopathy Questionnaire (range, 0-100; higher scores are better). Caregiver burden was assessed using the Oberst Caregiving Burden Scale, which measures time on task (OCBS-time) and task difficulty (OCBS-difficulty; range, 1-5; lower scores are better). Measurements occurred before surgery and 12 months after in 3 advanced heart failure cohorts: patients receiving long-term left ventricular assist device support; heart transplantation with pretransplant left ventricular assist device support; and heart transplantation without pretransplant left ventricular assist device support. Multivariable linear regression was used to identify predictors of change in OCBS-time and OCBS-difficulty at 12 months., Results: Of 162 caregivers, the mean age was 61.0±9.4 years, 139 (86%) were female, and 140 (86%) were the patient's spouse. At 12 months, 99 (61.1%) caregivers experienced improved OCBS-time, and 61 (37.7%) experienced improved OCBS-difficulty (versus no change or worse OCBS). A 10-point higher baseline 12-item Kansas City Cardiomyopathy Questionnaire predicted lower 12-month OCBS-time (β=-0.09 [95% CI, -0.14 to -0.03]; P <0.001) and OCBS-difficulty (β=-0.08 [95% CI, -0.12 to -0.05]; P <0.001). Each 10-point improvement in the 12-item Kansas City Cardiomyopathy Questionnaire predicted lower 12-month OCBS-time (β=-0.07 [95% CI, -0.12 to -0.03]; P =0.002) and OCBS-difficulty (β=-0.09 [95% CI, -0.12 to -0.06]; P <0.001)., Conclusions: Among survivors at 12 months, baseline and change in patient health status were associated with subsequent caregiver time on task and task difficulty in dyads receiving advanced heart failure surgical therapies, highlighting the potential for serial 12-item Kansas City Cardiomyopathy Questionnaire assessments to identify caregivers at risk of increased burden., Registration: URL: https://www.clinicaltrials.gov; unique identifier: NCT02568930., Competing Interests: Dr Grady is the principal investigator of grants from the National Heart, Lung, and Blood Institute; receives speaker fees from the American Heart Association; and served on the Board of Directors for the International Society for Heart and Lung Transplantation. Dr Spertus is the principal investigator of grants from Myokardia and Janssen; is a consultant to Myokardia, Bristol Meyers Squibb, Merck, Novartis, Pfizer, and Janssen; serves on the Scientific Advisory Board of United Healthcare and the Board of Directors for Blue Cross Blue Shield of Kansas City; and owns the copyright to the Kansas City Cardiomyopathy Questionnaire, Seattle Angina Questionnaire, and Peripheral Artery Questionnaire. The other authors report no conflicts.

Background: Quantifying guideline-directed medical therapy (GDMT) intensity is foundational for improving heart failure (HF) care. Existing measures discount dose intensity or use inconsistent weighting., Methods: The Kansas City Medical Optimization (KCMO) score is the average of total daily to target dose percentages for eligible GDMT, reflecting the percentage of optimal GDMT prescribed (range, 0-100). In Change the Management of Patients With HF, we computed KCMO, HF collaboratory (0-7), and modified HF Collaboratory (0-100) scores for each patient at baseline and for 1-year change in established GDMT at the time (mineralocorticoid receptor antagonist, β-blocker, ACE [angiotensin-converting enzyme] inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor). We compared baseline and 1-year change distributions and the coefficient of variation (SD/mean) across scores., Results: Among 4532 patients at baseline, mean KCMO, HF collaboratory, and modified HF Collaboratory scores were 38.8 (SD, 25.7), 3.4 (1.7), and 42.2 (22.2), respectively. The mean 1-year change (n=4061) for KCMO was -1.94 (17.8); HF collaborator, -0.11 (1.32); and modified HF Collaboratory, -1.35 (19.8). KCMO had the highest coefficient of variation (0.66), indicating greater variability around the mean than the HF collaboratory (0.49) and modified HF Collaboratory (0.53) scores, reflecting higher resolution of the variability in GDMT intensity across patients., Conclusions: KCMO measures GDMT intensity by incorporating dosing and treatment eligibility, provides more granularity than existing methods, is easily interpretable (percentage of ideal GDMT), and can be adapted as performance measures evolve. Further study of its association with outcomes and its usefulness for quality assessment and improvement is needed., Competing Interests: Disclosures Drs Khan and Sherrod are supported by the National Heart, Lung, and Blood Institute under award T32H110837. Dr Ikemura received an unrestricted research grant for the Department of Cardiology, Keio University School of Medicine from Bristol Myer Squibb. Dr Sauer reports industry relationships with Abbott, Boston Scientific, Biotronik, Bayer, Amgen, CSL Vifor, Acorai, Story Health, General Prognostics, Impulse Dynamics, and Edwards Lifesciences. He also serves as advisory board member and owns stock in ISHI digital health company. Dr Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr Butler reports consulting for Abbott, American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Roche, Sequana, SQ Innovation, and Vifor. Dr DeVore reports research funding through his institution from Biofourmis, Bodyport, Cytokinetics, American Regent Inc, the National Institutes of Health and the National Heart, Lung, and Blood Institute, Novartis, and Story Health. He also provides consulting services for and/or receives honoraria from Abiomed, Cardionomic, LivaNova, Natera, NovoNordisk, Story Health, and Zoll. Dr Lund is supported by Karolinska Institutet, the Swedish Research Council (grant 523-2014-2336), the Swedish Heart Lung Foundation (grants 20150557 and 20190310), and the Stockholm County Council (grants 20170112 and 20190525). Dr Lund reports the following relationships with industry: grants, consulting, honoraria: Abbot, Alleviant, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Edwards, Merck/MSD, Novartis, Novo Nordisk, OrionPharma, Owkin, Pharmacosmos, Vifor Pharma; stock ownership: AnaCardio. Dr Chan is supported by the National Heart, Lung, and Blood Institute under award R01HL160734 and is a consultant for Optum Rx. Dr Spertus has provided consultative services on patient-reported outcomes and evidence evaluation to Alnylam, AstraZeneca, Bayer, Merck, Janssen, Bristol Myers Squibb, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, 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. The other authors report no conflicts.

Background: Sodium glucose co-transporter 2 inhibitor (SGLT2i) therapy improves health status in heart failure (HF). There is insufficient description regarding the timing, rate, and extent of the health status changes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) after initiation of SGLT2is., Objectives: The authors sought to model the association of canagliflozin treatment with rates of change in HF symptom status in HFpEF and HFrEF., Methods: Study participants with HFrEF and HFpEF were treated with either canagliflozin 100 mg or placebo for 12 weeks. The Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) was assessed at baseline and at 2, 4, 6, and 12 weeks. Longitudinal modeling assessed slope of KCCQ change across the study., Results: Among 448 individuals with HF (181 with HFrEF and 267 with HFpEF), participants with HFpEF had lower baseline KCCQ-TSS scores than those with HFrEF (54 ± 21 vs 64 ± 20). Modeling demonstrated initial rapid improvement in KCCQ-TSS in both HF groups, with deceleration over the next 4 to 6 weeks. The rate of change was greater among HFpEF participants (0.7 points/day; 95% CI: 0.3-1.1 points/day) than HFrEF participants (ΔKCCQ-TSS/day = 0.5; 95% CI: 0.1-1.0 points/day) randomized to canagliflozin, but these differences were not statistically significant (0.2 points/day; 95% CI: -0.4 to 0.7 points/day; P = 056)., Conclusions: After canagliflozin therapy, regardless of EF, modeling shows the KCCQ-TSS improves rapidly with the greatest improvements occurring within the first weeks of treatment. These results have implications for clinical use of SGLT2is and may be useful in the design of trials examining impact of these agents on health status in HF. (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure [CHIEF-HF]; NCT04252287)., Competing Interests: Funding Support and Author Disclosures Dr Mohebi is supported by the Barry fellowship, and Dr Januzzi is supported in part by the Hutter Family Professorship. The CHIEF-HF study was supported by Janssen Scientific Affairs, LLC. Dr Januzzi is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott, Applied Therapeutics, HeartFlow, Innolife, and Roche Diagnostics; has received consulting income from Abbott, Beckman, Boehringer Ingelheim, Bristol Myers Squibb, Jana Care, Janssen, Merck, Novartis, Pfizer, Roche Diagnostics, and Siemens; and has participated in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, CVRx, Intercept, and Takeda. Dr Spertus has provided consultative services on patient-reported outcomes and evidence evaluation to Alnylam, AstraZeneca, Bayer, Merck, Janssen, Bristol Meyers Squibb, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, Imbria, and United Healthcare; holds research grants from Bristol Meyers 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. Dr Lingvay has received research funding (paid to institution) from NovoNordisk, Sanofi, Merck, Pfizer, Mylan, and Boehringer-Ingelheim. Dr Lingvay has received advisory/consulting fees and/or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer-Ingelheim, Johnson and Johnson, Intercept, TARGETPharma, Merck, Pfizer, Valeritas, Zealand Pharma, Shionogi, Carmot Therapeutics, Structure Therapeutics, Bayer, Translational Medical Academy, Mediflix, and WebMD. Dr Lanfear is supported in part by National Institutes of Health grants (P50MD017351 and R01HL132154); he is a consultant for Amgen, Janssen, Ortho Diagnostics, Cytokinetics, AstraZeneca, Otsuka, Abbot Laboratories, Illumina, and DCRI (Novartis); and he has participated in research from Akros, Novartis, Amgen, Lilly, AstraZeneca, Pfizer, Bayer, Illumina, Somalogic, and Janssen. 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: Clinical practice guidelines recommend optimizing the health status of patients with atrial fibrillation (AF) as a primary treatment goal. Whether disease-specific health status is associated with subsequent clinical events is unknown., Objectives: The aim of this study was to investigate the association between health status and subsequent clinical events among patients with AF., Methods: Using a prospective cohort study of patients with new-onset AF referred to 11 hospitals (n = 3,313, 68.4% men, mean age 67.8 ± 11.6 years), data were extracted from 3,296 patients (99.4%) who completed the disease-specific Atrial Fibrillation Effects on Quality-of-Life (AFEQT) questionnaire between 2012 and 2018. Factors associated with baseline AFEQT overall summary (OS) score and associations between major adverse cardiovascular or neurologic events (MACNE; a composite of all-cause death, stroke, or new-onset heart failure hospitalization) over 2 years were investigated., Results: Overall, 517 participants (15.6%) had poor to fair health status (AFEQT OS <60), and 1,035 (31.2%) had fair to good health status (AFEQT OS 60 to <80) at baseline. Female sex, younger age, family history of AF, higher baseline heart rate, paroxysmal AF, initial visit to the emergency department, and history of heart failure were associated with lower AFEQT OS scores. Of those, 226 participants (6.8%) experienced MACNE; restricted cubic spline analysis with adjustment for factors associated with baseline AFEQT score showed a nonlinear increase in the risk for MACNE with AFEQT OS score <80. The strongest associations were observed for baseline AFEQT daily activity scores (for AFEQT daily activity score of <80 vs ≥80, HR: 1.65; 95% CI: 1.21-2.25)., Conclusions: Diminished health status in patients with AF is common and is independently associated with subsequent adverse cardiovascular events., Competing Interests: Funding Support and Author Disclosures This study was funded by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (grants 20H03915, 20J01755, and 21K16069) and by an unrestricted research grant from Bayer Yakuhin. Dr Ikemura has received an unrestricted research grant for the Department of Cardiology, Keio University School of Medicine, from Bristol Myers Squibb. Dr Kohsaka has received an unrestricted research grant to the Department of Cardiology at Keio University School of Medicine from Bayer, Novartis, and Daiichi Sankyo; and has received personal fees from Bristol Myers Squibb. Dr Kimura has received grants from Bayer Yakuhin. Dr Takatsuki has received grants and personal fees from Bayer; and has received personal fees from Daiichi Sankyo and Bristol Myers Squibb. 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.)

Objectives: This study sought to determine whether the increased use of telehealth was associated with a difference in outcomes for outpatients with heart failure., Background: The COVID-19 pandemic led to dramatic changes in the delivery of outpatient care. It is unclear whether increased use of telehealth affected outcomes for outpatients with heart failure., Methods: In March 2020, a large Midwestern health care system, encompassing 16 cardiology clinics, 16 emergency departments, and 12 hospitals, initiated a telehealth-based model for outpatient care in the setting of the COVID-19 pandemic. A propensity-matched analysis was performed to compare outcomes between outpatients seen in-person in 2018 and 2019 and via telemedicine in 2020., Results: Among 8,263 unique patients with heart failure with 15,421 clinic visits seen from March 15 to June 15, telehealth was employed in 88.5% of 2020 visits but in none in 2018 or 2019. Despite the pandemic, more outpatients were seen in 2020 (n = 5,224) versus 2018 and 2019 (n = 5,099 per year). Using propensity matching, 4,541 telehealth visits in 2020 were compared with 4,541 in-person visits in 2018 and 2019, and groups were well matched. Mortality was similar for telehealth and in-person visits at both 30 days (0.8% vs 0.7%) and 90 days (2.9% vs 2.4%). Likewise, there was no excess in hospital encounters or need for intensive care with telehealth visits., Conclusions: A telehealth model for outpatients with heart failure allowed for distanced encounters without increases in subsequent acute care or mortality. As the pressures of the COVID-19 pandemic abate, these data suggest that telehealth outpatient visits in patients with heart failure can be safely incorporated into clinical practice., Competing Interests: Funding Support and Author Disclosures Dr Spertus is the principal investigator of grants from National Institutes of Health, Abbott Vascular, and the American College of Cardiology Foundation; is a consultant to Janssen, Novartis, Amgen, Myokardia, AstraZeneca, Bayer, and Merck; serves on the Scientific Advisory Board of United Healthcare and the Board of Directors for Blue Cross Blue Shield of Kansas City; owns the copyright to the Kansas City Cardiomyopathy Questionnaire, Seattle Angina Questionnaire, and Peripheral Artery Questionnaire; and has an equity interest in Health Outcomes Sciences. Dr Sperry is a consultant to Pfizer and Alnylam. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Health status outcomes are increasingly being promoted as measures of health care quality, given their importance to patients. In heart failure (HF), an American College of Cardiology/American Heart Association Task Force proposed using the proportion of patients with preserved health status as a quality measure but not as a performance measure because risk adjustment methods were not available., Methods: We built risk adjustment models for alive with preserved health status and for preserved health status alone in a prospective registry of outpatients with HF with reduced ejection fraction across 146 US centers between December 2015 and October 2017. Preserved health status was defined as not having a ≥5-point decrease in the Kansas City Cardiomyopathy Questionnaire Overall Summary score at 1 year. Using only patient-level characteristics, hierarchical multivariable logistic regression models were developed for 1-year outcomes and validated using data from 1 to 2 years. We examined model calibration, discrimination, and variability in sites' unadjusted and adjusted rates., Results: Among 3932 participants (median age [interquartile range] 68 years [59-75], 29.7% female, 75.4% White), 2703 (68.7%) were alive with preserved health status, 902 (22.9%) were alive without preserved health status, and 327 (8.3%) had died by 1 year. The final risk adjustment model for alive with preserved health status included baseline Kansas City Cardiomyopathy Questionnaire Overall Summary, age, race, employment status, annual income, body mass index, depression, atrial fibrillation, renal function, number of hospitalizations in the past 1 year, and duration of HF (optimism-corrected C statistic=0.62 with excellent calibration). Similar results were observed when deaths were ignored. The risk standardized proportion of patients alive with preserved health status across the 146 sites ranged from 62% at the 10th percentile to 75% at the 90th percentile. Variability across sites was modest and changed minimally with risk adjustment., Conclusions: Through leveraging data from a large, outpatient, observational registry, we identified key factors to risk adjust sites' proportions of patients with preserved health status. These data lay the foundation for building quality measures that quantify treatment outcomes from patients' perspectives.

Background: The Kansas City Cardiomyopathy Questionnaire (KCCQ) has been psychometrically evaluated in multiple heart failure (HF) populations, but the comparability of its psychometric properties between men and women is unknown., Methods: Data from 3 clinical trials (1 in stable HF with preserved ejection fraction, 1 each in stable and acute HF with reduced ejection fraction) and 1 prospective cohort study (stable HF with reduced ejection fraction), incorporating 6773 men and 3612 women with HF, were used to compare the construct validity, internal and test-retest reliability, ability to detect change, predict mortality and hospitalizations and minimally important differences between the 2 sexes. Interactions of the KCCQ overall summary and subdomain scores by sex were independently examined., Results: The KCCQ-Overall Summary score correlated well with New York Heart Association functional class in both sexes across patients with stable (correlation coefficient: -0.40 in men versus -0.49 in women) and acute (-0.37 in men versus -0.34 in women) HF. All KCCQ subdomains demonstrated concordant relationships with relevant comparison standards with no significant interactions by sex in 19 of 21 of these construct validity analyses. All KCCQ scores were equally predictive and other psychometric evaluations showed similar results by sex: test-retest reliability (intraclass correlation coefficient 0.94 in men versus 0.92 in women), responsive to change (standardized response mean 1.01 in both sexes), as were the minimally important differences and internal reliability., Conclusions: The psychometric properties of the KCCQ, in terms of validity, prognosis, reliability, and sensitivity to change, are comparable in men and women with HF with preserved ejection fraction and HF with reduced ejection fraction.

Introduction: Evaluation of health status benefits, cost-effectiveness, and value of new heart failure therapies is critical for supporting their use. The Kansas City Cardiomyopathy Questionnaire (KCCQ) measures patients' heart failure-specific health status but does not provide utilities needed for cost-effectiveness analyses. We mapped the KCCQ scores to EQ-5D scores so that estimates of societal-based utilities can be generated to support economic analyses., Methods: Using data from two US cohort studies, we developed models for predicting EQ-5D utilities (3L and 5L versions) from the KCCQ (23- and 12-item versions). In addition to predicting scores directly, we considered predicting the five EQ-5D health state items and deriving utilities from the predicted responses, allowing different countries' health state valuations to be used. Model validation was performed internally via bootstrap and externally using data from two clinical trials. Model performance was assessed using R2, mean prediction error, mean absolute prediction error, and calibration of observed vs. predicted values., Results: The EQ-5D-3L models were developed from 1000 health status assessments in 547 patients with heart failure and reduced ejection fraction (HFrEF), while the EQ-5D-5L model was developed from 3925 patients with HFrEF. For both versions, models predicting individual EQ-5D items performed as well as those predicting utilities directly. The selected models for the 3L had internally validated R2 of 48.4-50.5% and 33.7-45.6% on external validation. The 5L version had validated R2 of 57.7%., Conclusion: Mappings from the KCCQ to the EQ-5D can yield the estimates of societal-based utilities to support cost-effectiveness analyses when EQ-5D data are not available., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Heart failure is a common and devastating complication of type 2 diabetes (T2D). Prompt recognition of heart failure may avert hospitalization, facilitate use of guideline-directed therapies, and impact choice of T2D medications. We sought to determine the rate and factors associated with heart failure documentation in T2D patients with evidence of volume overload requiring loop diuretics., Methods: DCR is an on-going, prospective US registry of outpatient T2D patients from > 5000 cardiology, endocrinology, and primary care clinicians (current analysis used data from 2013-2019). Among T2D patients receiving loop diuretics, we examined the rate of chart documentation of heart failure. We used a 3-level hierarchical logistic regression model (patients nested within physician within practice) to examine factors associated with heart failure diagnosis., Results: Among 1,322,640 adults with T2D, 225,125 (17.0%) were receiving a loop diuretic, of whom 91,969 (40.9%) had documentation of heart failure. Male sex, lower body mass index, atrial fibrillation, chronic kidney disease, and coronary artery disease were associated with greater odds of heart failure diagnosis. After accounting for patient factors, patients seen by cardiologists were the most likely to have HF documented followed by PCPs and then endocrinologists., Conclusions: Among US outpatients with T2D, 17% of patients had evidence of volume overload-defined by loop diuretic prescription-of whom fewer than half had a clinical diagnosis of heart failure. While there may be non-heart failure indications for loop diuretics, our data suggest that a substantial proportion of T2D patients may have unrecognized heart failure and therefore could be missing opportunities for targeted therapies that could alter the clinical course of heart failure.

Importance: While there is increasing emphasis on incorporating patient-reported outcome measures in routine care for patients with heart failure (HF), how best to interpret longitudinally collected patient-reported outcome measures is unknown., Objective: To examine the strength of association between prior, current, or a change in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores with death and hospitalization in patients with HF with preserved (HFpEF) and reduced (HFrEF) ejection fractions., Design, Setting, and Participants: Secondary analyses of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial of 1372 patients with HFpEF, conducted between August 2006 and January 2012, and the HF-ACTION trial that included 1669 patients with HFrEF, conducted between April 2003 and February 2007., Exposures: Prior, current, and change in KCCQ Overall Summary scores (KCCQ-os) in 5-point increments (higher scores indicate better health status)., Main Outcomes and Measures: Time to cardiovascular death/first HF hospitalization (primary outcome) and all-cause death (secondary outcome)., Results: Of 1767 eligible TOPCAT participants, 882 were women (49.9%), and the mean (SD) age was 71.5 (9.7) years. Of 2130 eligible HF-ACTION participants, 599 were women (28.1%), and the mean age was 58.6 (12.7) years. Each 5-point difference in prior or current KCCQ-os scores was associated with a 6% (95% CI, 4%-8%; P < .001) to 9% (95% CI, 7%-11%; P < .001) lower risk for subsequent cardiovascular death/first HF hospitalization in patients with HFpEF and 6% (95% CI, 4%-9%; P < .001) to 8% (95% CI, 5%-10%; P < .001) lower risk for subsequent cardiovascular death/first HF hospitalization in patients with HRpEF and HFrEF in unadjusted analyses. Results were similar for change in KCCQ-os. In models with the prior and current KCCQ-os, only the current KCCQ-os was significantly associated with 10% (95% CI, 7%-12%; P < .001) and 7% (95% CI, 3%-11%; P < .001) lower risk for subsequent cardiovascular death/first HF hospitalization in patients with HFpEF and HFrEF, respectively. Similar results were observed when the current and Δ KCCQ-os were considered together, when adjusted for important patient and treatment characteristics, when including 3 sequential KCCQ-os scores, and when examining all-cause death as the outcome., Conclusions and Relevance: In serial health status evaluations of patients with HF, the most recent KCCQ score was most strongly associated with subsequent death and cardiovascular hospitalization in HFpEF and HFrEF. Measuring serial patient-reported outcome measures in the clinical care of patients with HF can provide an updated assessment of prognosis., Trial Registration: clinicaltrials.gov Identifier: NCT00094302 (TOPCAT) and NCT00047437 (HF-ACTION).

Background: Missing health-related quality of life (HRQOL) data in longitudinal studies can reduce precision and power and bias results. Using INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support), we sought to identify factors associated with missing HRQOL data, examine the impact of these factors on estimated HRQOL assuming missing at random missingness, and perform sensitivity analyses to examine missing not at random (MNAR) missingness because of illness severity., Methods and Results: INTERMACS patients (n=3248) with a preimplantation profile of 1 (critical cardiogenic shock) or 2 (progressive decline) were assessed with the EQ-5D-3L visual analog scale and Kansas City Cardiomyopathy Questionnaire-12 summary scores pre-implantation and 3 months postoperatively. Mean and median observed and missing at random-imputed HRQOL scores were calculated, followed by sensitivity analyses. Independent factors associated with HRQOL scores and missing HRQOL assessments were determined using multivariable regression. Independent factors associated with preimplantation and 3-month HRQOL scores, and with the likelihood of missing HRQOL assessments, revealed few correlates of HRQOL and missing assessments ( R 2 range, 4.7%-11.9%). For patients with INTERMACS profiles 1 and 2 and INTERMACS profile 1 alone, missing at random-imputed mean and median HRQOL scores were similar to observed scores, before and 3 months after implantation, whereas MNAR-imputed mean scores were lower (≥5 points) at baseline but not at 3 months., Conclusions: We recommend use of sensitivity analyses using an MNAR imputation strategy for longitudinal studies when missingness is attributable to illness severity. Conduct of MNAR sensitivity analyses may be less critical after mechanical circulatory support implant, when there are likely fewer MNAR data., (© 2017 American Heart Association, Inc.)

Background: Quantifying quality of life (QoL) after left ventricular assist device (LVAD) remains challenging. Heart failure (HF)-specific health status measures are ideal for assessing symptoms of HF; however, if patients' QoL is limited by other factors, they may experience improved HF-specific QoL but no concurrent improvement in generic QoL. We sought to examine and predict discrepancies between disease-specific and generic QoL measures after LVAD., Methods: We examined HF-specific and generic QoL with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQol-5D Visual Analog Scale (VAS), respectively, among 1,888 patients with advanced heart failure who underwent LVAD implantation from 2012 to 2014 as part of the INTERMACS registry., Results: Both measures showed substantial improvement, on average, at 6 months after LVAD, with mean changes of 32.7 ± 25.0 and 27.6 ± 27.4, respectively. Among the 1,539 patients (81.5%) with moderate/large improvement in KCCQ, 334 (21.7%) had discordant changes in generic QoL (i.e., VAS did not substantially increase despite improvement in KCCQ). In a multivariable logistic regression model, baseline VAS score was the strongest predictor of KCCQ-VAS discordance, whereas post-LVAD complications were not significant predictors of discordance., Conclusions: Most patients have major improvements in both HF-specific and generic QoL after LVAD implantation, and discordance in these measures after LVAD is uncommon. When it did occur, discordance was primarily observed in patients who reported good generic QoL on the VAS before LVAD (despite substantial impairment due to congestive HF). These results support the continued use of HF-specific health status measures to monitor QoL before and after LVAD implantation., (Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Clinical trials have established the average benefit of cardiac resynchronization therapy (CRT), but estimating benefit for individual patients remains difficult because of the heterogeneity in treatment response. Accordingly, we created a multivariable model to predict changes in quality of life (QoL) with and without CRT., Methods and Results: Patient-level data from 5 randomized trials comparing CRT with no CRT were used to create a prediction model of change in QoL at 3 months using a partial proportional odds model for no change, small, moderate, and large improvement, or deterioration of any magnitude. The C statistics for not worsening or obtaining at least a small, moderate, and large improvement were calculated. Among the 3614 patients, regardless of assigned treatment, 33.3% had a deterioration in QoL, 9.2% had no change, 9.2% had a small improvement, 13.5% had a moderate improvement, and the remaining 34.9% had a large improvement. Patients undergoing CRT were less likely to have a decrement in their QoL (28.2% versus 38.9%; P <0.001) and more likely to have a large QoL improvement (38.7% versus 30.6%; P <0.001). A partial proportional odds model identified baseline QoL, age, and an interaction of CRT with QRS duration as predictors of QoL benefits 3 months after randomization. C statistics of 0.65 for not worsening, 0.68 for at least a small improvement, 0.69 for at least a moderate improvement, and 0.73 for predicting a large improvement were observed., Conclusions: There is marked heterogeneity of treatment benefit of CRT that can be predicted based on baseline QoL, age, and QRS duration., (© 2017 American Heart Association, Inc.)

Background: Atrial fibrillation (AF) and heart failure with reduced ejection fraction frequently coexist. The AATAC (Ablation versus Amiodarone for Treatment of persistent Atrial fibrillation in patients with Congestive heart failure and an implantable device) trial suggests that catheter ablation may benefit these patients. However, applicability to contemporary ambulatory cardiology practice is unknown., Methods and Results: Using the outpatient National Cardiovascular Data Registry ® Practice Innovation and Clinical Excellence Registry, we identified participants meeting AATAC enrollment criteria between 2013 and 2014. Treatment with medications and procedures was assessed at registry inclusion. From 164 166 patients with AF and heart failure, 8483 (7%) patients potentially met AATAC inclusion criteria. Eligible subjects, compared to AATAC trial participants, were older (mean age, 71.2±11.4 years) and had greater comorbidity (coronary artery disease 79.2%, hypertension 82.4%, and diabetes mellitus 31.8%). AF was predominantly paroxysmal (65.5%), rather than persistent/permanent (16.7%) or new onset (17.8%), whereas all patients in the AATAC trial had persistent AF. Commonly used atrioventricular-nodal blocking agents were carvedilol (71.2%), digoxin (31.9%), and metoprolol (27.1%). Rhythm control with anti-arrhythmic drugs was reported in 29.0% of AATAC eligible patients (predominantly amiodarone [24.6%]) and 9.3% had undergone catheter ablation. Patients who underwent ablation were more likely to be younger and have less comorbidities than those who did not., Conclusions: Among the contemporary ambulatory AF/heart failure with reduced ejection fraction population, treatment is predominantly rate control with few catheter ablations. Application of AATAC findings has the potential to markedly increase the use of catheter ablation in this population, although significant differences in clinical profiles might influence ablation outcomes in practice., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objectives: This study sought to assess the performance of the HeartMate Risk Score (HMRS) in a large multicenter cohort, with a focus on its performance as a function of disease severity., Background: The HMRS has been proposed as a simple tool for risk stratification of LVAD recipients, but subsequent studies have challenged its validity., Methods: We performed a retrospective, longitudinal, comparative study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) database. The HMRS was calculated for each patient and its association with mortality was assessed using Cox models, including a pre-specified interaction by INTERMACS profile groups (1 vs. 2 vs. 3 vs 4+)., Results: Among 10,847 patients with a mean age of 57.0 ± 12.9 years, 78.9 % were male; and 14.1%, 37.4%, 30.4%, and 18.2% were in INTERMACS profile groups 1, 2, 3, and ≥4, respectively. The HMRS showed moderate discrimination for both short-term (90-day, C-index 0.62) and long-term (2-years, C-index 0.60) mortality, with no significant difference between axial and centrifugal devices. Patients in the highest HMRS group had a relative risk of 90-day mortality 2.8 times greater than those in the lowest HMRS group (13.0% vs. 4.7%; p < 0.001). Importantly, the relative risks of higher HMRS scores were similar across INTERMACS profile groups, with subgroups of patients in INTERMACS profile 1 and 2 having comparable or lower mortality than some in INTERMACS profile 4+., Conclusions: The HMRS is a valid means of risk-stratifying patients across all INTERMACS profiles and may be superior to traditional INTERMACS classification. Risk stratification with the HMRS showed that patients within each INTERMACS profile groups have a wide spectrum of mortality risk and low INTERMACS profiles should therefore not be considered a contraindication to mechanical support., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Interpreting the clinical significance of changes in patient-reported outcomes (PROs) is critically important. The most commonly used approach is to anchor mean changes on PRO scores against a global assessment of change. Whether the assessor of global change should be patients or their physicians is unknown. We compared patients' and physicians' assessments of change over time to examine which was more aligned with patients' changes in PRO measures., Methods: A total of 459 chronic heart failure patients aged >30 years were enrolled from 13 US centers. Data were obtained by medical record abstraction, physical assessments, and patient interviews at a baseline clinic visit and 6 weeks later. Health status was measured with the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ), and both patients and physicians completed a validated 15-level global assessment of change, ranging from large deterioration to large improvement., Results: There was substantial variation between physicians/patients' global assessment of clinical change (weighted kappa = 0.36, 95 % CI 0.28, 0.43). Overall, physician assessments were more strongly correlated with change on the KCCQ summary score than were patients' assessments (physician R = 0.37, patient R = 0.29)., Conclusion: There was substantial variation between patients' and physicians' global assessment of 6-week change in heart failure status. Physician assessments of the importance of clinical changes were more strongly associated with changes in all domains of patient-reported health status, as assessed by the KCCQ, and may provide a more consistent method for defining the clinical importance of changes in patients' health status.

Background: A left ventricular assist device (LVAD) improves survival and quality of life for many, but not all, patients with end-stage heart failure who are ineligible for transplantation. We sought to evaluate the frequency of poor outcomes using a novel composite measure that integrates quality of life with mortality., Methods and Results: Within the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) national registry, poor outcome was defined as death or an average Kansas City Cardiomyopathy Questionnaire <45 during the year after LVAD (persistently limiting heart failure symptoms and poor quality of life). Among 1638 patients with LVAD, 29.7% had a poor outcome, with death in 22.4% and persistently poor quality of life in 7.3%. Patients who had a poor outcome were more likely to have higher body mass indices (29.3 versus 28.2 kg/m(2); P=0.007), lower hemoglobin levels (11.1 versus 11.4 g/dL; P=0.005), previous cardiac surgery (47.8% versus 39.8%; P=0.004), history of cancer (13.8% versus 9.7%; P=0.025), severe diabetes mellitus (15.6% versus 11.5%; P=0.038), and poorer quality of life preimplant (Kansas City Cardiomyopathy Questionnaire scores: 29.8 versus 35.3; P<0.001)., Conclusions: Nearly one third of patients die or have a persistently poor quality of life during the year after LVAD. We identified several factors associated with a poor outcome, which may inform discussions before LVAD implantation to enable more realistic expectations of recovery., (© 2016 American Heart Association, Inc.)

Background: Given the importance of patients' health-related quality of life (HRQL) after mechanical circulatory support (MCS) device implantation, the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) collects the Kansas City Cardiomyopathy Questionnaire (KCCQ) before and after MCS. The success of data collection and potential implications of missing data on HRQL analyses are unknown., Methods: We examined the frequency and reasons for not collecting baseline and 3-month KCCQ data across INTERMACS sites from May 2012 to December 2013. Hierarchical logistic regression was used to examine site variability (median odds ratios [MOR]) for not collecting KCCQ data to demonstrate the degree to which some sites can collect more complete data than others., Results: Among 3960 and 3523 patients participating in INTERMACS before and 3 months after left ventricular assist device implantation, the KCCQ was not collected in 43.1% at baseline (range across sites, 0-100%) and 40.9% (range, 0-100%) at follow-up. The most common reasons for incomplete KCCQ data at baseline were that the patient was too sick (13.9%) and consent to participate in research was not obtained (12.4%). Significant variation across sites was observed for missingness because of patient (MOR, 2.8; P < .001) and administrative (MOR, 4.8; P < .001) reasons. The most variable patient reasons were that the patients were too stressed (MOR, 7.2; P < .001) and too busy (MOR, 10.6; P < .001). The most variable administrative reasons were that the coordinator was too busy/forgot (MOR, 7.1; P < .001) and miscellaneous reasons (MOR, 8.7; P < .001). At 3 months, significant variation persisted for both patient (MOR, 2.7; P < .001) and administrative (MOR, 3.5; P < .001) reasons. The most variability across sites was that the patient was too busy (MOR, 6.0, P < .001) and that the coordinator was too busy/forgot (MOR, 5.8; P < .001)., Conclusions: Sites vary substantially in collecting KCCQ data, and many of these variations seem addressable. Improving the consistency of HRQL data collection can improve the value of INTERMACS in defining the patient-centered benefits of MCS treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The objective of this study is to examine practice-level variation in rates of guideline-recommended treatment for outpatients with heart failure and reduced ejection fraction, and to examine the association between treatment variation and practice site, independent of patient factors., Methods and Results: Cardiology practices participating in the National Cardiovascular Disease Registry Practice Innovation and Clinical Excellence registry from July 2008 to December 2010 were evaluated. Practice rates of treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and β-blockers and an optimal combined treatment measure were determined for patients with heart failure and reduced ejection fraction and no documented contraindications. Multivariable hierarchical regression models were adjusted for demographics, insurance status, and comorbidities. A median rate ratio was calculated for each therapy, which describes the likelihood that the treatment of a patient with given comorbidities would differ at 2 randomly selected practices. We identified 12 556 patients from 45 practices. The unadjusted practice-level prescription rates ranged from 44% to 100% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (median, 85%; interquartile range, 75%-89%), from 49% to 100% for β-blockers (median, 92%; interquartile range, 83%-95%), and from 37% to 100% for optimal combined treatment (median, 79%; interquartile range, 66%-85%). The adjusted median rate ratio was 1.11 (95% confidence interval, 1.08-1.18) for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers therapy, 1.08 (95% confidence interval, 1.05-1.15) for β-blockers therapy, and 1.17 (1.13-1.26) for optimal combined treatment., Conclusions: Variation in the use of guideline-recommended medications for patients with heart failure and reduced ejection fraction exists in the outpatient setting. Addressing practice-level differences may be an important component of improving quality of care for patients with heart failure and reduced ejection fraction.

Background: Despite the growing epidemic of heart failure with preserved ejection fraction (HFpEF), no valid measure of patients' health status (symptoms, function, and quality of life) exists. We evaluated the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of HF with reduced EF, in patients with HFpEF., Methods and Results: Using a prospective HF registry, we dichotomized patients into HF with reduced EF (EF≤ 40) and HFpEF (EF≥50). The associations between New York Heart Association class, a commonly used criterion standard, and KCCQ Overall Summary and Total Symptom domains were evaluated using Spearman correlations and 2-way ANOVA with differences between patients with HF with reduced EF and HFpEF tested with interaction terms. Predictive validity of the KCCQ Overall Summary scores was assessed with Kaplan-Meier curves for death and all-cause hospitalization. Covariate adjustment was made using Cox proportional hazards models. Internal reliability was assessed with Cronbach's α. Among 849 patients, 200 (24%) had HFpEF. KCCQ summary scores were strongly associated with New York Heart Association class in both patients with HFpEF (r=-0.62; P<0.001) and HF with reduced EF (r=-0.55; P=0.27 for interaction). One-year event-free rates by KCCQ category among patients with HFpEF were 0 to 25=13.8%, 26 to 50=59.1%, 51 to 75=73.8%, and 76 to 100=77.8% (log rank P<0.001), with no significant interaction by EF (P=0.37). The KCCQ domains demonstrated high internal consistency among patients with HFpEF (Cronbach's α=0.96 for overall summary and ≥0.69 in all subdomains)., Conclusions: Among patients with HFpEF, the KCCQ seems to be a valid and reliable measure of health status and offers excellent prognostic ability. Future studies should extend and replicate our findings, including the establishment of its responsiveness to clinical change.

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.)

Background: Although a variety of prognostic tools have been shown to predict rehospitalization and mortality in heart failure patients, their utility in assessing future costs is less clear. We assessed whether health status assessment with the Kansas City Cardiomyopathy Questionnaire (KCCQ) predicts future costs in stable heart failure outpatients with left ventricular dysfunction after myocardial infarction., Methods and Results: We evaluated 12-month cost utilization data from 1516 heart failure outpatients enrolled in the Quality-of-Life Substudy of the Eplerenone Post-Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Multivariable hierarchical models assessed whether the KCCQ (categorized as 0 to <25, 25 to <50, 50 to <75, and 75 to 100) was an independent predictor of future resource use. At baseline, 685 patients (45.2%) had good health status (KCCQ scores > or =75), whereas 510 (33.6%), 262 (17.3%), and 59 (3.9%) had fair (KCCQ, 50 to 74), poor (KCCQ, 25 to 49), and the worst (KCCQ <25) health status, respectively. After multivariable adjustment, compared with patients with good health status, patients with fair health status incurred incremental 1-year costs of $1520 (cost ratio, 1.23; 95% confidence interval, 1.05 to 1.43), whereas patients with poor and the worst health status incurred incremental 1-year costs of $4265 (cost ratio, 1.63; 95% confidence interval, 1.34 to 1.99) and $8999 (cost ratio, 2.34; 95% confidence interval, 1.62 to 3.38), respectively (P<0.0001 for association with KCCQ). Further adjustment for New York Heart Association class led to only partial attenuation of this relationship (P=0.0002)., Conclusions: Health status assessment predicts resource use and costs over the next year in stable heart failure outpatients with left ventricular dysfunction after myocardial infarction.

Background: While generic health status measures quantify the impact of all patients' diseases on their health-related quality of life, disease specific measures focus on only one of the many conditions that a patient may have. If a patient has two diseases with similar clinical manifestations, they may respond differently to a disease-specific instrument if one of their conditions improves while the other worsens or remains stable, thus undermining the instruments in that patient population. We sought empirical evidence of the reliability and validity (including responsiveness) of the Kansas City Cardiomyopathy Questionnaire (KCCQ), a disease-specific measure for heart failure (HF), among HF patients with and without anemia, a condition that has similar symptoms to HF., Methods: This work used a prospective cohort study of 811 HF outpatients from 58 U.S. centers with a baseline assessment of anemia of whom 698 were followed for 3 months with serial health status measures., Results: Among participants, 268 (33%) were anemic. The construct validity of the KCCQ was supported by showing similar correlations with the New York Heart Association (NYHA) classification in patients with and without anemia (P value for interaction = 0.38). The internal consistency (Cronbach's alpha = 0.92 and 0.93 for anemic and non-anemic patients, respectively) and test-retest reliability (mean 3-month change scores in stable patients = -2.8 [SD = 1.4] and -0.5 [SD = 0.8], P = 0.14) were similar. Estimates of responsiveness were also similar., Conclusion: This study provides empirical evidence that the psychometric properties of the KCCQ are similar in patients with or without anemia, a potentially confounding clinical condition in patients with heart failure.

Background: Studies have identified anemia as a potential therapeutic target in patients with heart failure, with the goal of improving survival and health status. However, whether changes in hematocrit are associated with changes in health status is unknown., Methods and Results: We studied 1382 patients with heart failure after myocardial infarction who had serial hematocrits and health status assessments with the Kansas City Cardiomyopathy Questionnaire (KCCQ). Linear regression models assessed the relationship between change in hematocrit and change in health status between 1 month (baseline) and 3 months after hospitalization. During follow-up, 12.6% of patients experienced a greater than 2% decline in hematocrit, 32.5% experienced a greater than 2% improvement in hematocrit, and 54.9% had no significant hematocrit change. After multivariable adjustment there was a highly significant interaction (P = .007) between baseline hematocrit and change in hematocrit, suggesting that the effects of changes in hematocrit on health status vary as a function of patients' initial hematocrits. Patients with severe anemia initially (hematocrit < or = 33%) experienced marked decrements in health status (-4.4 point KCCQ change per 1% hematocrit decline, P = .006) with further declines in hematocrit, but only modest health status gains with hematocrit improvements (0.6 point KCCQ change per 1% hematocrit improvement, P = .3). Less pronounced changes were observed among patients with a baseline hematocrit greater than 33% to 39%, and no significant changes were seen in patients with hematocrit levels greater than 39%., Conclusion: Among anemic patients with heart failure, a decrease in hematocrit is associated with marked decline in health status, whereas health status gains associated with hematocrit improvements are modest.

Background: Identification of heart failure outpatients at increased risk for clinical deterioration remains a critical challenge, with few tools currently available to assist clinicians. We tested whether serial health status assessments with the Kansas City Cardiomyopathy Questionnaire (KCCQ) can identify patients at increased risk for mortality and hospitalization., Methods and Results: We evaluated 1358 patients with heart failure after an acute myocardial infarction in the Eplerenone's Neurohormonal Efficacy and Survival Study, a multicenter randomized trial that included serial KCCQ assessments. Cox proportional-hazards models were used to examine whether changes in KCCQ scores during successive outpatient visits were independently associated with all-cause mortality and cardiovascular mortality or hospitalization. Change in KCCQ (deltaKCCQ) was linearly associated with all-cause mortality (hazard ratio [HR], for each 5-point decrease in deltaKCCQ, 1.11; 95% CI, 1.04 to 1.19) and the combined outcome of cardiovascular mortality or hospitalization (HR for each 5-point decrease in deltaKCCQ, 1.12; 95% CI 1.07 to 1.18). In Kaplan-Meier survival analysis, all-cause mortality among patients with deltaKCCQ of < or = -10, > -10 to < 10, and > 10 points was 26%, 16%, and 13%, respectively (P=0.008). After multivariable adjustment, the linear relationship between deltaKCCQ and both all-cause mortality and combined cardiovascular death and hospitalization persisted (HR, 1.09; 95% CI, 1.00 to 1.18; and HR, 1.11; 95% CI, 1.05 to 1.17 for each 5-point decrease in deltaKCCQ, respectively)., Conclusions: In heart failure outpatients, serial health status assessments with the KCCQ can identify high-risk patients and may prove useful in directing the frequency of follow-up and the intensity of treatment.

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.

Background: To evaluate whether depressive symptoms are independently predictive of mortality and hospitalization among patients with acute myocardial infarction (AMI) complicated by heart failure., Methods: The EPHESUS trial enrolled patients with AMI complicated by heart failure. Patients from Canada, the UK, and the United States completed a Medical Outcomes Study-Depression questionnaire at baseline in addition to a comprehensive clinical examination. Cox proportional hazards regression was used to determine the relationship between depressive symptoms and outcomes, including 2-year all-cause mortality and cardiovascular death or hospitalization, adjusting for baseline clinical variables., Results: Overall, 143 of 634 patients (22.6%) had significant depressive symptoms at baseline (Medical Outcomes Study-Depression score > or = 0.06). Depressed patients had higher 2-year mortality (29% vs 18%; P = .004) and cardiovascular death or hospitalization (42% vs 33%; P = .016). After risk adjustment, depressive symptoms remained significantly associated with mortality (hazard ratio 1.75, 95% CI 1.15-2.68, P = .01) and cardiovascular death or hospitalization (hazard ratio 1.41, 95% CI 1.03-1.93, P = .03). Results were consistent across demographic and clinical subgroups., Conclusions: Depression is an independent predictor of all-cause mortality and cardiovascular death or hospitalization after AMI complicated by heart failure. Although many factors may mediate outcomes in patients with AMI, studies are warranted to evaluate whether a depression intervention can improve survival and/or reduce hospitalizations.

Background: Although B-type natriuretic peptide (BNP) levels have been proposed as a means of assessing disease severity in patients with heart failure, it is not known if BNP levels are correlated with health status (symptom burden, functional limitation, and quality of life)., Methods and Results: We studied 342 outpatients with systolic heart failure from 14 centers at baseline and 6 +/- 2 weeks with BNP levels and the Kansas City Cardiomyopathy Questionnaire (KCCQ), a heart-failure-specific health status instrument. We assessed the correlation between KCCQ scores and BNP at baseline and changes in KCCQ according to changes in BNP levels between baseline and follow-up. Mean baseline BNP levels were 379 +/- 387 pg/mL and mean KCCQ summary scores were 62 +/- 23 points. Although baseline BNP and KCCQ were both associated with New York Heart Association classification (P < .001 for both), BNP and KCCQ were not correlated (r(2) = 0.008, P = .15). There was no significant relationship between changes in BNP and KCCQ regardless of the threshold used to define a clinically meaningful BNP change. For example, using >50% BNP change threshold, KCCQ improved by 3.7 +/- 14.2 in patients with decreasing BNP, improved by 1.7 +/- 13.6 in patients with no BNP change, and improved by 1.0 +/- 13.4 in patients with increasing BNP (P = .6)., Conclusion: BNP and health status are not correlated in outpatients with heart failure in the short term. This suggests that these measures may assess different aspects of heart failure severity, and that physiologic measures do not reflect patients' perceptions of the impact of heart failure on their health status.

The determinants of change in left ventricular (LV) ejection fraction (EF) over time in patients with impaired LV function at baseline have not been clearly established. Using a nuclear database to assess changes in LV function over time, we included patients with a baseline LVEF of 25% to 40% on a gated single-photon emission computed tomographic study at rest and only if second-gated photon emission computed tomography performed approximately 18 months after the initial study showed an improvement in LVEF at rest of > or =10 points or a decrease in LVEF at rest of > or =7 points. In all, 148 patients qualified for the EF increase group and 59 patients for the EF decrease group. LVEF on average increased from 33 +/- 4% to 51 +/- 8% in the EF increase group and decreased from 35 +/- 4% to 25 +/- 5% in the EF decrease group. The strongest multivariable predictor of improvement of LVEF was beta-blocker therapy (odds ratio 3.9, p = 0.002). The strongest independent predictor of LVEF decrease was the presence of a permanent right ventricular apical pacemaker (odds ratio 6.6, p = 0.002). Thus, this study identified beta-blocker therapy as the major independent predictor for improvement in LVEF of > or =10 points, whereas a permanent pacemaker (right ventricular apical pacing) was the strongest predictor of a LVEF decrease of > or =7 points.

Background: The importance of repeated clinical assessments of patients with heart failure is widely accepted. The frequency of such follow-up is not established and is likely to depend on the natural history and variability of patients' health status and the availability and use of appropriate treatments., Methods and Results: We analyzed data from a multicenter prospective cohort study of heart failure outpatients comparing baseline variables including New York Heart Association (NYHA) class, summary score on the Kansas City Cardiomyopathy Questionnaire (KCCQ), and performance on a 6-minute walk test with results of a repeat evaluation at 6 weeks. We also compared patient and physician assessment of change in disease status among patients with advanced symptoms (NYHA class III with a recent antecedent hospitalization or class IV) and those with milder degrees of limitation (NYHA classes I, II, and stable III). Patients with advanced symptoms had greater short-term variability in health status as reflected by the KCCQ summary score and a visual analog scale. A greater proportion of patients with advanced heart failure experienced moderate or greater clinical change. Patient and physician global assessments were congruent with more direct measures of health status., Conclusion: Patients with advanced heart failure have greater short-term variability in status, supporting the need for frequent clinical follow-up and appropriate power calculations for clinical trials that are designed to measure meaningful changes over a short period.

IntroductionEvaluation of health status benefits, cost-effectiveness, and value of new heart failure therapies is critical for supporting their use. The Kansas City Cardiomyopathy Questionnaire (KCCQ) measures patients' heart failure-specific health status but does not provide utilities needed for cost-effectiveness analyses. We mapped the KCCQ scores to EQ-5D scores so that estimates of societal-based utilities can be generated to support economic analyses.MethodsUsing data from two US cohort studies, we developed models for predicting EQ-5D utilities (3L and 5L versions) from the KCCQ (23- and 12-item versions). In addition to predicting scores directly, we considered predicting the five EQ-5D health state items and deriving utilities from the predicted responses, allowing different countries' health state valuations to be used. Model validation was performed internally via bootstrap and externally using data from two clinical trials. Model performance was assessed using R2, mean prediction error, mean absolute prediction error, and calibration of observed vs. predicted values.ResultsThe EQ-5D-3L models were developed from 1000 health status assessments in 547 patients with heart failure and reduced ejection fraction (HFrEF), while the EQ-5D-5L model was developed from 3925 patients with HFrEF. For both versions, models predicting individual EQ-5D items performed as well as those predicting utilities directly. The selected models for the 3L had internally validated R2 of 48.4-50.5% and 33.7-45.6% on external validation. The 5L version had validated R2 of 57.7%.ConclusionMappings from the KCCQ to the EQ-5D can yield the estimates of societal-based utilities to support cost-effectiveness analyses when EQ-5D data are not available.

Background: The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial demonstrated that higher-risk patients with atrial fibrillation had lower rates of stroke or systemic embolism and a similar rate of major bleeding, on average, when treated with dabigatran 150mg compared to warfarin. Since population-level averages may not apply to individual patients, estimating the heterogeneity of treatment effect can improve application of RE-LY in clinical practice. Methods and results: For 18040 patients randomized in RE-LY, we used patient-level data to develop multivariable models to predict the risk for stroke or systemic embolism and for major bleeding including all three treatment groups (dabigatran 110mg, dabigatran 150mg, and warfarin) over a median follow up of 2.0 years. The mean predicted absolute risk reduction (ARR) for stroke/systemic embolism with dabigatran 150mg compared to warfarin was 1.32% (range 11.6% lower to 3.30% higher risk). The mean predicted ARR for bleeding was 0.41% (range 8.93% lower to 63.4% higher risk). Patients with increased stroke/systemic embolism risk included those with prior stroke/TIA (OR 2.01), diabetics on warfarin (OR 2.00), and older patients on dabigatran 150mg (OR 1.68 for every 10-year increase). Major bleeding risk was higher in patients on aspirin (OR 1.25), with a history of diabetes (OR 1.34) or prior stroke/TIA (OR 1.22), those with heart failure on dabigatran 110mg (OR 1.52), older patients on either dabigatran 110mg or 150mg (OR 1.57 and 1.93, respectively, for each 10-year increase), and heavier patients on dabigatran 110mg or 150mg; patients in a region outside the United States and Canada and with better renal function had lower bleeding risk. Conclusions: There is substantial heterogeneity in the benefits and risks of dabigatran relative to warfarin among patients with atrial fibrillation. Using individualized estimates may enable shared decision making and facilitate more appropriate use of dabigatran; as such, it should be prospectively tested. Clinical trial registration: www.clinicaltrials.gov number, NCT00262600. [ABSTRACT FROM AUTHOR]

Background: Some studies suggest that female practitioners are more likely to provide guideline-concordant care than male practitioners; however, little is known about the role of practitioner gender in cardiology. Objective: The aim of the study was to measure the association between practitioner gender and adherence to the cardiovascular performance measures in the American College of Cardiology's ambulatory Practice Innovation and Clinical Excellence Registry. Methods: Patients with at least 1 outpatient visit with a unique practitioner were included. Among eligible patients, adherence to 7 guideline-supported performance measures for coronary artery disease, heart failure, and atrial fibrillation over 12 months after registry entry was compared by practitioner gender using hierarchical models adjusting for practitioner type (physicians vs advance practice practitioners) and number of visits. Results: The study cohort included 1493 individual practitioners who saw 769 139 patients; 80% of practitioners were men. Male practitioners were more often physicians compared with female practitioners (98.2% vs 43.7%, P < .01). Accounting for practitioner category and visit frequency, guideline adherence rates were similar by practitioner gender for all measures with the exception of marginally higher rates for coronary artery disease performance measures for male practitioners compared with female practitioners (antiplatelet: rate ratio [RR] = 1.06; 95% confidence interval [CI], 1.03-1.09; "-blockers: RR = 1.06; 95% CI, 1.01-1.10; and lipid-lowering drug: RR = 1.07; 95% CI, 1.04-1.10) and atrial fibrillation (oral anticoagulants: RR = 1.05; 95% CI, 1.01-1.09). Conclusion: Male practitioners marginally outperformed their female counterparts in ambulatory practices enrolled in a voluntary cardiovascular performance improvement registry program. Overall low adherence to some performance measures suggests room for improvement among all practitioners. [ABSTRACT FROM AUTHOR]

Background: There is a growing demand to collect patients' experiences of their health status (their symptoms, function, and quality of life) in clinical trials, quality assessment initiatives, and in routine clinical care. In heart failure, the 23-item, disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ) has been shown to be valid, reliable, sensitive to clinical change, and prognostic of both clinical events and costs. However, its use has been limited, in part, by its length. We sought to develop a shortened version of the instrument that maintains the psychometric properties of the full KCCQ.Methods and Results: Using data from 3 clinical studies incorporating 4168 patients, we derived and validated a 12-item KCCQ, the KCCQ-12, to capture symptom frequency, physical and social limitations, and quality of life impairment as a result of heart failure, as well as an overall summary score. The KCCQ-12 scores had high correlations with the original scales (>0.93 for all scales in all clinical settings), high test–retest reliability (>0.76 for all domains), high responsiveness (16–31 point improvements after discharge from hospitalization; standardized response mean =0.61–1.12), and comparable prognostic significance and interpretation of clinically important differences as compared with the full KCCQ.Conclusions: The KCCQ-12 is a shorter version of the original 23-item instrument that should be more feasible to implement while preserving the psychometric properties of the full instrument. [ABSTRACT FROM AUTHOR]

Abstract: Background: Little is known about medication nonadherence in heart failure populations. We evaluated the association between 1 aspect of medication nonadherence, patient-reported difficulty taking medications as directed, and health status among heart failure outpatients, and then examined whether this association was explained by depression. Methods and Results: A total of 522 outpatients with left ventricular ejection fraction <0.40 completed clinical evaluation, Kansas City Cardiomyopathy Questionnaire (KCCQ), Medical Outcomes Study-Depression questionnaire, and categorized their difficulty taking medications (5-level Likert-scale question). Multivariable regression was used to evaluate the cross-sectional association between difficulty taking medications and health status, with incremental adjustment for medical history and depressive symptoms. Patients with difficulty taking medications (n = 64; 12.2%) had worse health status (8.2 ± 2.7 point lower mean KCCQ summary scores; P = .008) and more depressive symptoms (43.8% versus 27.1%; P = .006). Adjusting for demographic and clinical factors had little effect on the association between difficulty taking medications and health status (8.0 ± 3.2 point lower KCCQ scores; P = .01); however, the relationship was attenuated with adjustment for depressive symptoms (4.7 ± 2.9 point lower KCCQ scores; P = .11). Conclusions: Among heart failure outpatients, difficulty taking medications is associated with worse health status. This association appears to be explained, in part, by coexistent depression. Future studies should evaluate interventions such as depression treatment to improve medication adherence and health status. [Copyright &y& Elsevier]

Background Survival and health status (eg, symptoms and quality of life) are key outcomes in clinical trials of heart failure treatment. However, health status can only be recorded on survivors, potentially biasing treatment effect estimates when there is differential survival across treatment groups. Joint modeling of survival and health status can address this bias. Methods and Results We analyzed patient-level data from the PARTNER 1B trial (Placement of Aortic Transcatheter Valves) of transcatheter aortic valve replacement versus standard care. Health status was quantified with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at randomization, 1, 6, and 12 months. We compared hazard ratios for survival and mean differences in KCCQ scores at 12 months using several models: the original growth curve model for KCCQ scores (ignoring death), separate Bayesian models for survival and KCCQ scores, and a Bayesian joint longitudinal-survival model fit to either 12 or 30 months of survival follow-up. The benefit of transcatheter aortic valve replacement on 12-month KCCQ scores was greatest in the joint-model fit to all survival data (mean difference, 33.7 points; 95% credible intervals [CrI], 24.2-42.4), followed by the joint-model fit to 12 months of survival follow-up (32.3 points; 95% CrI, 22.5-41.5), a Bayesian model without integrating death (30.4 points; 95% CrI, 21.4-39.3), and the original growth curve model (26.0 points; 95% CI, 18.7-33.3). At 12 months, the survival benefit of transcatheter aortic valve replacement was also greater in the joint model (hazard ratio, 0.50; 95% CrI, 0.32-0.73) than in the nonjoint Bayesian model (0.54; 95% CrI, 0.37-0.75) or the original Kaplan-Meier estimate (0.55; 95% CI, 0.40-0.74). Conclusions In patients with severe symptomatic aortic stenosis and prohibitive surgical risk, the estimated benefits of transcatheter aortic valve replacement on survival and health status compared with standard care were greater in joint Bayesian models than other approaches. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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). 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) [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Background: Previous studies have described an “obesity paradox” with heart failure, whereby higher body mass index (BMI) is associated with lower mortality. However, little is known about the impact of obesity on survival after acute myocardial infarction. Methods: Data from 2 registries of patients hospitalized in the US with acute myocardial infarction between 2003-2004 (PREMIER) and 2005-2008 (TRIUMPH) were used to examine the association of BMI with mortality. Patients (n=6359) were categorized into BMI groups (kg/m2) using baseline measurements. Two sets of analyses were performed using Cox proportional hazards regression with fractional polynomials to model BMI as categorical and continuous variables. To assess the independent association of BMI with mortality, analyses were repeated, adjusting for 7 domains of patient and clinical characteristics. Results: Median BMI was 28.6. BMI was inversely associated with crude 1-year mortality (normal, 9.2%; overweight, 6.1%; obese, 4.7%; morbidly obese; 4.6%; P <.001), which persisted after multivariable adjustment. When BMI was examined as a continuous variable, the hazards curve declined with increasing BMI and then increased above a BMI of 40. Compared with patients with a BMI of 18.5, patients with higher BMIs had a 20% to 68% lower mortality at 1 year. No interactions between age (P =.37), sex (P =.87), or diabetes mellitus (P =.55) were observed. Conclusions: There appears to be an “obesity paradox” among patients after acute myocardial infarction such that higher BMI is associated with lower mortality, an effect that was not modified by patient characteristics and was comparable across age, sex, and diabetes subgroups. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]