utility of the kansas city cardiomyopathy questionnaire...

Utility of the Kansas City Cardiomyopathy Questionnaire for Monitoring

Health Status in Patients with Aortic Stenosis

Arnold et al: KCCQ in Patients with Aortic Stenosis

Suzanne V. Arnold MD MHA*; John A. Spertus MD MPH*; Yang Lei MS*;

Keith B. Allen MD*; Adnan K. Chhatriwalla MD*; Martin B. Leon MD†;

Craig R. Smith MD†; Matthew R. Reynolds MD MSc‡; John G. Webb MD§;

Lars G. Svensson MD¶; David J. Cohen MD MSc*

*Saint Luke’s Mid America Heart Institute, Kansas City, MO; †Columbia-Presbyterian Hospital, New York, NY; ‡Harvard Clinical Research Institute, Boston, MA; §University of British Columbia and St. Paul’s Hospital, Vancouver, BC, Canada; ¶Cleveland Clinic Foundation, Cleveland, OH Correspondence to Suzanne V. Arnold MD MHA Saint Luke’s Mid America Heart Institute 4401 Wornall Rd Kansas City, MO 64111 Phone: 816-932-8606 Fax: 816-932-5613 Email: [email protected] DOI: 10.1161/CIRCHEARTFAILURE.112.970053

Journal Subject Codes: [19] Valvular heart disease, [100] Health policy and outcome research, [11] Other heart failure, [23] Catheter-based coronary and valvular interventions: other

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Abstract

Background—Improving functional status and quality of life are important goals of treatment

for patients with severe aortic stenosis. The Kansas City Cardiomyopathy Questionnaire (KCCQ)

is a health status measure designed for monitoring heart failure and has been used in studies of

patients with aortic stenosis (AS). However, its psychometric properties have not yet been

evaluated in patients with severe valvular heart disease.

Methods and Results—We analyzed data from 955 patients who were enrolled in the

PARTNER trial of transcatheter aortic valve replacement (TAVR) to evaluate the reliability,

responsiveness, validity, and prognostic importance of the KCCQ in patients with severe AS.

The KCCQ was administered to all patients at baseline and at 1, 6, and 12 months after

randomization to medical therapy, TAVR, or surgical valve replacement. Among patients who

were clinically stable, there were only small changes in the KCCQ domain scores over time

(mean differences 0.1 to 4.2 points), and the intraclass correlation coefficients for the domains

showed good agreement between paired assessments (0.65-0.76). In contrast, the domain scores

of patients who underwent TAVR showed large changes after treatment (mean differences 13-30

points). The construct validity of each of the domains was demonstrated by comparing the

domains against relevant reference measures (Spearman correlations 0.46-0.69). Finally, among

157 patients who were randomized to medical management, lower KCCQ overall summary

scores at baseline were strongly associated with an increased risk of mortality over the following

12 months, even after adjusting for STS mortality risk score (HR 1.34 per 10 point reduction,

95% CI 1.17-1.54).

Conclusions—The KCCQ is a highly reliable, responsive, and valid measure of symptoms,

functional status, and quality of life in patients with severe, symptomatic AS.

Key Words: quality of life, aortic stenosis, heart failure, valves

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Aortic stenosis (AS) is prevalent among the elderly and, once symptoms develop, is associated

with considerable risk of morbidity and mortality. Although surgical aortic valve replacement

(AVR) has been considered the “gold standard” therapy for patients with symptomatic AS,

transcatheter aortic valve replacement (TAVR) has recently emerged as a less invasive

therapeutic option. While TAVR has been shown to have a substantial mortality advantage over

medical therapy in patients who are considered to be too high-risk for surgical AVR,1, 2 for many

of these patients who are very elderly and have multiple comorbid conditions, improvements in

symptoms and quality of life may be more important goals of therapy.3, 4 As such, a thorough

understanding of health status outcomes should be an integral part of any study examining

treatment options for severe AS, including TAVR.5

Currently, there are no instruments designed specifically for the assessment of health

status and quality of life among patients with AS. Previous studies have used either generic

health status measures (such as the SF-36 or EuroQol-5D) or relatively crude scales such as the

New York Heart Association (NYHA) classification scheme.6-8 These scales have a number of

important limitations, however, including limited responsiveness to clinically important changes

and reliance on external assessors (rather than the patients themselves). Although patients with

severe AS may experience angina or syncope as their major presenting symptom, heart failure

symptoms are predominant among patients presenting for AVR.9, 10 As such, use of a heart-

failure-specific instrument has been suggested as a potentially useful approach for this

population.5 The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific

instrument originally developed to describe and monitor health status in patients with heart

failure.11 The KCCQ has undergone extensive reliability and validity testing in various heart

failure populations11-13 and has been shown to predict mortality14 and healthcare costs15 in such

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patients. However, its psychometric properties have not been evaluated in patients with AS. We

therefore designed a secondary analysis of a series of clinical trials to assess the reliability,

responsiveness, validity, and prognostic importance of the KCCQ among patients with severe AS

undergoing a range of therapeutic approaches as part of the Placement of Aortic Transcatheter

Valves (PARTNER) trial.

Methods

Patient Population

Patients for our validation study were drawn from the PARTNER trial of patients with severe

symptomatic AS who were being considered as potential candidates for TAVR. Full details of

the study inclusion and exclusion criteria have been described previously.1, 16 Enrolled patients

were required to have severe AS (defined as an aortic-valve area of <0.8 cm2 with either a mean

aortic-valve gradient of 40 mmHg or a /peak aortic-jet velocity of 4.0 m/s); New York Heart

Association (NYHA) class II, III, or IV heart failure symptoms; and high surgical risk based on

the Society for Thoracic Surgeons (STS) risk score. Depending on the assessment of 2 cardiac

surgeons, eligible patients were classified as either high risk but suitable for surgical aortic valve

replacement (cohort A)16 or ineligible for cardiac surgery due to coexisting medical conditions

associated with a predicted probability of death or permanent disability 50% (Cohort B).1

Cohort A patients were randomized to undergo either surgical AVR or TAVR, whereas Cohort B

patients were randomized to TAVR vs. medical therapy. The study was approved by the

institutional review board at each participating site, and all patients provided written informed

consent.

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Health Status and Clinical Assessment

Patients were assessed for clinical factors and health status at baseline and at 1, 6, and 12 months

after randomization. Health status, which includes symptoms, functional status, and quality of

life, was evaluated with the KCCQ, the Medical Outcomes Study Short-Form 12 (SF-12) Health

Survey, and the EuroQol-5D.17 Linguistically and culturally validated translations of the

questionnaires were provided to non-English speakers. Disease-specific health status was

assessed with the KCCQ,11 a 23-item self-administered questionnaire that addresses specific

health domains pertaining to heart failure: physical limitation, symptoms, quality of life, social

limitation, symptom stability, and self-efficacy—the first 4 of which are combined into an

overall summary scale. Values for the domains range from 0 to 100 with higher scores indicating

lower symptom burden and better quality of life. The self-efficacy domain is designed to assess

whether or not a patient feels they have the knowledge and skills to manage their heart failure as

an outpatient. Since patients with severe AS often have symptoms and hospitalizations that are

unrelated to their knowledge of their disease, the self-efficacy domain of the KCCQ does not

apply to patients with AS and thus was excluded from these analyses. The symptom stability

domain uses a single question to assess the change in the patient’s heart failure symptoms over

the past 2 weeks. As such, longitudinal analyses of this domain are difficult to interpret (i.e., a

change of a change). This domain was thus excluded from the reliability and responsiveness

analyses.

Generic health status was assessed with the SF-12 and EuroQol-5D. The SF-12 is a

reliable and valid measure of generic health status that provides summary component scales for

overall physical (PCS) and mental (MCS) health.18 Scores are standardized using norm-based

methods to generate a mean of 50 and a standard deviation of 10, with higher scores indicating

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better health status.19 The EuroQol-5D is a 5-item instrument that assesses specific domains of

health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.20 Responses

to these questions were converted to utility weights according to an algorithm developed for the

U.S. population.21, 22 In addition to patient-reported health status, patients were assessed for

NYHA functional class and the distance covered during a 6-minute walk test at baseline and at

each of the follow-up time points.

Statistical Analysis

Determining Questionnaire Reliability. Internal consistency of the KCCQ domains was assessed

using Cronbach’s alpha. All patients at baseline were included in this analysis (n=940). Values of

the Cronbach’s alpha statistic range from 0-1 and reflect the consistency of different items within

each individual domain. In general, 0.9 indicates excellent consistency; 0.9 > 0.8 is quite

good; 0.8 > 0.7 is acceptable; 0.7 > 0.6 is questionable; and 0.6 > is poor.23

To test the instrument’s test-retest reproducibility, we first identified a cohort that was

clinically stable throughout the period of observation. This cohort was comprised of patients who

were 12 months post-TAVR, had no hospitalizations in the prior 6 months, and had no change in

NYHA functional class from 6 to 12 months. A total of 152 patients met the inclusion criteria for

the stable cohort. Domain scores at 6 and 12 months were then compared using paired t-tests.

Reproducibility was further examined with the intraclass correlation coefficient,24 which is the

ratio of between-groups variance to total variance. The ICC ranges from 0 to 1 with higher

scores indicating increased test-retest reliability. In general, an ICC 0-0.2 indicates poor

agreement, 0.3-0.4 indicates fair agreement, 0.5-0.6 indicates moderate agreement, 0.7-0.8

indicates strong agreement, and >0.8 indicates excellent agreement.25

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Determining Questionnaire Responsiveness. The responsiveness of the KCCQ domains

to a clinical change was first assessed among patients who underwent TAVR and were alive at 1

month after the procedure (n=419). Scores at baseline and 1 month were compared using paired

t-tests. Cohen’s d effect size,26 which quantifies the magnitude of change relative to baseline

variation, was also used to assess the responsiveness of the questionnaire to clinical change. In

general, an effect size of 0.2 to 0.3 indicates a small effect; ~0.5 is a medium effect; and 0.8 is a

large effect.27

To examine the sensitivity of the KCCQ to clinically relevant changes and its ability to

discriminate between different levels of change, we calculated the change in domain scores for

all patients from baseline to 1 month (n=761) stratified by their change in NYHA class over the

same time period and examined the relationship between the change in domain scores vs. the

change in NYHA class using a linear trend test.

Determining Questionnaire Validity. The validity of the different domains was tested by

comparing the domains with other measures that quantify similar concepts. For the symptom

stability domain, we compared 2 cohorts of patients at 1 month: a stable cohort of 15 patients

who were medically managed, had no interval hospitalizations and no change in NYHA class

from baseline to 1 month; and an unstable cohort of 347 patients who underwent TAVR and had

an improvement in NYHA class from baseline to 1 month. Symptom stability scores at 1 month

were compared between the 2 groups using an independent t-test.

For all other domains, the analytic cohort consisted of all patients alive at 6 months after

randomization (n=739). For the KCCQ physical limitations domain, we examined the correlation

with the 6-minute walk test, the SF-12 PCS, and NYHA functional class. For the KCCQ

symptoms domain and the overall summary score, we examined their correlations with NYHA

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functional class. Finally, we examined the correlations between both the KCCQ quality of life

and social limitations scales and the SF-12 MCS. The criterion standards chosen for these

comparisons closely mirror those used in the original validation of the KCCQ.11 Spearman's

rank correlation coefficients were used to test all correlations.

Prognostic Importance. The association between the KCCQ overall summary score and

survival was examined among patients who were randomized to medical therapy alone (n=157).

We first compared the mean baseline scores between patients who died (n=77) vs. those who

survived the 12 months after randomization (n=80) using independent t-tests. Cox proportional

hazard regression was used to evaluate the association between baseline scores as a continuous

variable (scaled per 10 points) and 12-month mortality, adjusting for the STS risk score which

incorporates multiple prognostically important demographic and clinical factors (e.g., age, sex,

multiple comorbidities, cardiac structure and function; Supplemental Table I) into a mortality

risk estimate. Finally, we examined the relationship between the KCCQ overall summary scale

as a categorical variable (0-25, 26-50, and >50)14 and 12-month survival using Kaplan-Meier

survival curves and the log-rank test. Cox regression was used to evaluate the association of

KCCQ scores as a categorical variable (Reference group: scores >50) with 12-month mortality

after adjusting for the STS mortality risk score.

All analyses were conducted using SAS v9.2 (SAS Institute, Inc., Cary, NC), and

statistical significance was determined by a 2-sided p-value of <0.05.

Results

Patient Population. The overall patient population was comprised of 955 patients with severe

AS (mean AVA=0.64 cm2). The mean age of the population was 84 years, 46% were female, the

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mean left ventricular ejection fraction was 53%, and 94% had NYHA Class 3 or 4 heart failure

symptoms. As participants in the PARTNER trial, a total of 157 patients were randomized to

medical therapy, 498 were assigned to TAVR, and 300 were assigned to surgical aortic valve

replacement (Table 1). Descriptions of the patients included in each of the analyses and the tests

used to assess each of the psychometric properties are shown in Table 2 and Supplemental Table

II.

Reliability of the KCCQ. The results of the internal consistency analysis of the domains

of the KCCQ are shown in Table 3. The quality of life domain demonstrated acceptable

consistency ( =0.72) while all other domains showed good or excellent consistency ( >0.8).

The reproducibility of the KCCQ among 159 patients who were clinically stable between

assessments is shown in Table 4. Serial assessments were similar between 6 and 12 months for

all domains except the Physical Limitations domain, in which the mean within-patient change in

scores decreased by 4.2 points (95% CI 0.9 to 7.4, p=0.013), although the ICC was high

suggesting greater inter-subject than within-subject variability. In fact, the ICC indicated

moderate-to-strong agreement between the 2 assessments for all domains, supporting the

reproducibility of the KCCQ in stable patients.

Responsiveness of the KCCQ. Among patients who underwent treatment for their AS

with TAVR, there were dramatic differences in the KCCQ scores before and after treatment

(Table 5). The symptom, quality of life, and overall summary domains of the KCCQ all showed

large effect sizes with the physical limitations and social limitations domains showing moderate

effect sizes. When all of the patients alive at 1 month were stratified by change in NYHA class

from baseline, the KCCQ demonstrated excellent discriminatory ability (Table 6). There was

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little difference in the change in KCCQ between those with a 2-class vs. 3-class decrease in

NYHA, possibly reflecting the coarseness of the NYHA measurement.

Validity of the KCCQ. The results of correlation analyses between the KCCQ domains

and relevant criterion standards (based on 6 month results for all scales) are summarized in Table

7. The Physical Limitations domain was significantly correlated with measures of functional

status including the 6-minute walk test (r=0.46), the SF-12 PCS (r=0.69), and NYHA class (r=-

0.49; p<0.0001 for all). The Quality of Life domain was highly correlated with measures of

generic health status including the SF-12 physical (r=0.52) and mental components (r=0.50) as

well as EuroQol-5D derived utilities (r=0.52; p<0.0001 for all). The Social Limitations domain

was highly correlated with the SF-12 mental component (r=0.50; p<0.0001). The KCCQ

Symptom scale and Overall Summary Score were highly correlated with NYHA class (r=-0.50

and -0.53, respectively; p<0.0001 for both; Figure 1). Finally, for the symptom stability scale,

comparison of 1-month scores between patients who were stable over the prior month vs. those

who had improved clinically demonstrated a substantial difference between the 2 groups, as

expected (stable vs. unstable: 48.3 vs. 72.3, p<0.0001).

Prognostic Importance. Over the 12 months following randomization, 77 of the 157

patients (49%) who were randomized to medical management died. At baseline, mean scores on

the KCCQ Overall Summary Scale of those patients who died were significantly lower than

those who were alive at 12 months (28.2 vs. 41.0, p<0.0001). In a Cox proportional hazards

model adjusted for STS mortality risk score, every 10 point decline in the KCCQ Overall

Summary Scale at baseline was associated with an 34% greater hazard of dying over the

following 12 months (HR 1.34, 95% CI 1.17-1.54, p<0.0001). Similar findings were noted in

categorical analyses in which there was a strong association between ranges of the baseline

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KCCQ summary scale and 12 month survival (Figure 2). Compared with patients who had

baseline scores >50, patients with scores of 25 faced a nearly 4-fold increased risk of dying

over the following 12 months, even after adjusting for the STS mortality risk score (HR 3.75,

95% CI 1.93-7.29, p<0.0001). The prognosis for patients with scores 26-50 did not differ

significantly from those with higher scores (HR 1.40, 95% CI 0.68-2.85, p=0.36).

Discussion

With the rapid development and expanded use of non-surgical approaches for treatment of

patients with severe aortic stenosis, there is an increasing need to understand the impact of these

innovative therapies on the short- and long-term quality of life of patients. While improved long-

term survival is a fundamental goal of treatment for patients with severe AS, improved health

status may be an equally important goal for the elderly, complex patients who are increasingly

considered candidates for such therapies. Indeed, for many such patients, therapies that lead to

improved survival without improved quality of life may not be considered worthwhile. As such,

it is critically important that studies of TAVR and its alternatives use a health status instrument

that reliably and validly quantifies the spectrum of symptoms, functional status, and quality of

life of patients with AS.

Previous studies have demonstrated that the KCCQ is a valid, sensitive, and

prognostically relevant tool for quantifying health status and quality of life in patients with heart

failure.11-15 Since heart failure symptoms are the predominant clinical manifestation of patients

with severe AS,9, 10 we hypothesized that the KCCQ could serve as a valid disease-specific

measure in such patients. In this study of nearly 1000 patients with severe symptomatic AS

undergoing a variety of treatment approaches for their AS, we found that the KCCQ retains its

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previously documented psychometric properties. In addition, we found that among patients who

were medically managed for their AS, KCCQ scores were strongly associated with long-term

mortality, even after adjusting for the STS mortality risk score that integrates multiple

prognostically important demographic and clinical characteristics, and thus could be used to help

inform patients’ expectations of the course of their disease.

Comparison with Prior Studies. The psychometric characteristics of the KCCQ in our

study were comparable to those observed in the original KCCQ validation study, with similar

internal consistency, reproducibility, responsiveness and construct validity.11 Importantly, the

mean age of our population was 84 years versus 64 years in the original validation cohort of

heart failure patients. Despite the older age of our population, the psychometric properties and

interpretability of the KCCQ were similar to those observed in prior studies of heart failure

patients. In addition to the original set of analyses, we also examined the sensitivity to change of

the KCCQ and its ability to discriminate between different levels of change and found that the

KCCQ also performed well in this regard. Of note, we did not include the self-efficacy domain in

our analyses as we felt that the domain questions, which are designed to assess a patient’s

knowledge and confidence in managing his or her disease, would not be as applicable to patients

with severe AS. There has been one study that examined the psychometric qualities of the

Minnesota Living with Heart Failure Questionnaire in 50 patients undergoing valve surgery, 11

of whom had aortic stenosis.28 By evaluating the scale at baseline and after surgery, as compared

with the SF-36, the authors found that this heart failure scale demonstrated acceptable internal

consistency, construct validity and responsiveness. Importantly, reliability, sensitivity to change,

and prognostic associations were not assessed in this small sample of patients with mixed

valvular heart disorders.

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The prognostic value of the KCCQ has been demonstrated previously among patient with

heart failure. In a cohort of 1516 patients with recent acute MI and heart failure or reduced left

ventricular function, Soto and colleagues reported that patients who had KCCQ Overall

Summary scores <25 had a 2-fold increased hazard of death or rehospitalization over the

following 11 months as compared with those with scores 75.14 Heidenreich and colleagues

reported similar findings in an outpatient heart failure population.29 In the PARTNER trial

population, we found that patients with severe AS and low KCCQ scores who were treated

medically had a nearly 4-fold higher risk of death over the following year as compared with

those with higher KCCQ scores. The stronger association with mortality seen in our study most

likely reflects both the older age of our patient population and the generally poorer prognosis of

patients with severe, symptomatic AS compared with the post-myocardial infarction heart failure

population that has been studied previously. Of note, we did not include rehospitalization in our

prognosis analyses given the high mortality rate (50% dead by 1-year) and the high frequency of

hospital admissions for procedures such as balloon aortic valvuloplasty.

Limitations. Our study should be interpreted in the context of several potential

limitations. First, virtually all of the patients in our study had advanced heart failure symptoms,

as indicated by the high prevalence of NYHA Class III or IV functional status at baseline. Thus,

it is unclear if our findings apply to patients with less severe symptomatic manifestations of heart

failure, although there is no a priori reason to expect that the KCCQ would be less valid in these

patients. It is important to note that many of the analyses were performed using data from 6-

month follow-up after TAVR or AVR, at which time there was a much broader range of

symptom levels and functional abilities, further underscoring the validity of the KCCQ in less

symptomatic AS patients. Second, not all KCCQ domains had independent reference standards

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for the validity analyses, so some domains were compared against the same metrics (e.g., the

quality of life and social limitations domains were compared against the SF-12 MCS). While we

still observed strong correlations with the corresponding measures demonstrating acceptable

validity of these domains, use of the more comprehensive SF-36 would have improved the

specificity of our validity testing. Moreover, there is no ‘gold standard’ for quantifying the

impact of a disease on patients’ perceptions of its impact on their function, symptoms and quality

of life. Finally, while we were able to assemble several appropriate patient groups in which to

test the psychometric properties of the KCCQ in severe AS patients, these analytic populations

were retrospectively constructed as secondary data analyses. As such, we were unable to

examine every facet of its psychometric properties, such as face and content validity, which

would need to be tested in a prospective manner.

Conclusions. Based on this study of patients from the PARTNER trial, the KCCQ

appears to be a reliable, responsive, and valid health status instrument for patients with aortic

stenosis. Importantly, the psychometric characteristics of the KCCQ were comparable to those

observed in the original KCCQ validation study performed in post-MI patients, despite

differences in the age of the population and primary disease process. Given the importance of

symptoms, functional status, and quality of life in elderly patients with severe AS, the KCCQ

should be considered a highly relevant and meaningful outcome for both clinical trials and

registry-based studies TAVR. In addition, given its prognostic value, the KCCQ could also serve

as an important tool in the clinical management of patients with severe AS. Future studies are

necessary to determine whether the KCCQ can help guide the appropriate timing of valve

intervention—both when symptoms and quality of life are impaired enough to intervene but

before patients are too sick to benefit from valve replacement.

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Sources of Funding

This study was self-funded.

Disclosures

John Spertus owns the copyright to the KCCQ. Martin Leon is a nonpaid member of the

Scientific Advisory Board of Edwards Lifesciences and has received travel reimbursement from

Edwards for activities related to his participation on the Executive Committee of the PARTNER

Trial. Craig Smith has received travel reimbursement from Edwards Lifesciences for activities

related to his participation on the Executive Committee of the PARTNER Trial. Matthew

Reynolds has received research support from Edwards Lifesciences, Biosense Webster, Sanofi-

Aventis; and consulting fees from Biosense Webster, Sanofi-Aventis, St. Jude Medical, and

Medtronic. John Webb has received consulting fees from Edwards Lifesciences and travel

reimbursement for activities related to his participation on the Executive Committee of the

PARTNER Trial. Lars Svensson has received travel reimbursement from Edwards Lifesciences

for activities related to his participation on the Executive Committee of the PARTNER Trial.

David Cohen has received research support from Edwards Lifesciences, Medtronic, Boston

Scientific, Abbott Vascular, MedRad, Merck/Schering-Plough, and Eli Lilly-Daiichi Sankyo;

consulting income from Schering-Plough, Eli Lilly, Medtronic, and Cordis; and speaking

honoraria from Eli Lilly, The Medicines Company, and St. Jude Medical. The other authors have

no potential conflicts to disclose.

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valve implantation clinical trials: A consensus report from th

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MS, MoMMMM on MMRRR, MMMenennenndded lofffffffff EEEEN,N,N,, HuHudddddddd leleston CCBBB, PPPasque MKMKM , ife after aortic vaaaalvlvlvve eeee rerererereplplplplp acaaaa emeeee enenenennt tttt atatatatat ttthehehehehe aaaagegegegege ooooof >80 years. Cir

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28. Supino PG, Borer JS, Franciosa JA, Preibisz JJ, Hochreiter C, Isom OW, Krieger KH, Girardi LN, Bouraad D, Forur L. Acceptability and psychometric properties of the minnesota living with heart failure questionnaire among patients undergoing heart valve surgery: Validation and comparison with sf-36. J Card Fail. 2009;15:267-277.

29. Heidenreich PA, Spertus JA, Jones PG, Weintraub WS, Rumsfeld JS, Rathore SS, Peterson ED, Masoudi FA, Krumholz HM, Havranek EP, Conard MW, Williams RE. Health status identifies heart failure outpatients at risk for hospitalization or death. J Am Coll Cardiol. 2006;47:752-756.

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Table 1. Baseline Demographic and Clinical Characteristics of the Analytic Population

Characteristic N=955

Age (y) 83.6 ± 7.3

Female 46.3%

Caucasian 93.2%

STS Mortality Risk Score (%) 11.6 ± 4.2

Aortic Valve Area (cm2) 0.64 ± 0.19

Mean Aortic Valve Gradient (mmHg) 43.4 ± 14.8

Ejection Fraction (%) 52.8 ± 13.8

Prior Myocardial Infarction 26.1%

Prior Bypass Graft Surgery 41.8%

Oxygen-Dependent Lung Disease 13.6%

Creatinine >2mg/dL 18.9%

NYHA Class

II 6.3%

III 44.5%

IV 49.2%

Treatment

Medical Management 16.4%

Surgical Valve Replacement 31.4%

Transcatheter Valve Replacement 52.1% STS, Society of Thoracic Surgeons

6.6.3%%%

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Table 2. Summary of Analytic Approaches

Attribute Patients Reference Measure Analysis

Internal Consistency All patients at baseline (n=955) Baseline KCCQ items Cronbach's alpha

Test-Retest Reliability Stable patients post-TAVR (n=152) 6M in KCCQ scores Paired t-test, Intraclass correlation coefficient

Responsiveness TAVR patients alive at 1M (n=419) 1M in KCCQ scores Paired t-test, Cohen's d

Sensitivity to Change All patients alive at 1M (n=761) 1M in KCCQ by in NYHA class Paired t-tests

Construct Validity

Physical Limitations All patients alive at 6M (n=739) 6MWT, NYHA class, SF-12 PCS Correlation

Symptom Scale All patients alive at 6M (n=739) NYHA class Correlation, Linear trend

Symptom Stability Stable MM patients at 1M (n=15); TAVR patients at 1M; (n=347)

1M scores of stable vs. unstable patients Two-sample independent t-test

Quality of Life All patients alive at 6M (n=739) SF-12 PCS, SF-12 MCS, EuroQol-5D Correlation

Social Limitation All patients alive at 6M (n=739) SF-12 MCS Correlation

Overall Summary Scale All patients alive at 6M (n=739) NYHA class Correlation, Linear trend

Prognostic Importance MM patients (n=157) Survival at 12M

Two-sample independent t-test (dead vs. alive), Cox

proportional hazards regression, Log-rank test

TAVR, transcatheter aortic valve replacement; KCCQ, Kansas City Cardiomyopathy Questionnaire; NYHA, New York Heart Association; MM, medical management; = change; M = months

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Table 3. Internal Consistency of the KCCQ Domains

Domain Cronbach's Alpha

Physical limitation 0.88

Symptoms 0.83

Quality of life 0.72

Social limitation 0.89

Overall summary 0.94

KCCQ, Kansas City Cardiomyopathy Questionnaire

0.9 indicates excellent consistency; 0.9> 0.8 is quite good; 0.8> 0.7 is acceptable; 0.7> 0.6 is questionable; and 0.6> is poor23



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Table 4. Six-Month Change in KCCQ Scores Among Patients in the Reliability Cohort (n=159)

6M Mean 12M Mean Mean Difference p-value ICC*

Physical limitation 68.6 65.6 -4.2 0.013 0.74

Symptoms 80.1 78.1 -1.9 0.138 0.65

Quality of life 79.7 79.8 0.1 0.954 0.69

Social limitation 73.2 73.0 0.6 0.781 0.71

Overall summary 76.1 74.5 -1.5 0.200 0.76

KCCQ, Kansas City Cardiomyopathy Questionnaire; ICC, Intraclass Correlation Coefficient *ICC 0-0.2 indicates poor agreement, ICC 0.3-0.4 is fair; ICC 0.5-0.6 is moderate; ICC 0.7-0.8 is strong; and >0.8 is excellent25



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Table 5. One-Month Change in KCCQ Scores Among Patients Who Underwent TAVR (n=419)

Baseline Mean 1M Mean Mean Difference p-value Effect Size*

Physical limitation 40.0 54.3 +12.9 <0.0001 0.51

Symptoms 49.4 68.5 +19.2 <0.0001 0.84

Quality of life 34.8 64.4 +29.7 <0.0001 1.16

Social limitation 32.0 54.1 +21.9 <0.0001 0.69

Overall summary 39.2 61.1 +22.0 <0.0001 0.94

KCCQ, Kansas City Cardiomyopathy Questionnaire * Effect size 0.2 to 0.3 indicates a small effect; ~0.5 is a medium effect; and 0.8 is a large effect27



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Table 6. Mean One-Month Change in KCCQ Score, Stratified by Change in NYHA Class

NYHA Change from Baseline to 1 Month

by 3 (n=79)

by 2 (n=255)

by 1 (n=278)

No change (n=146)

Worsening (n=28)

p-value for trend

Physical limitation 18.9 16.8 4.2 -0.5 -2.5 0.0003

Symptoms 26.4 24.3 13.0 6.2 -12.4 <0.0001

Quality of life 30.4 33.2 22.8 13.3 2.6 <0.0001

Social limitation 27.2 26.3 11.7 6.7 -6.7 <0.0001

Overall summary 27.0 26.0 14.4 6.7 -5.4 <0.0001

KCCQ, Kansas City Cardiomyopathy Questionnaire; NYHA, New York Heart Association

2.2.2.2.2.2.2 6 6 6 6 6 6 6

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Table 7. Convergent Validity Testing: Correlations of KCCQ Domains with Other Measures (n=739)

NYHA SF-12 PCS SF-12 MCS 6MWT EuroQol-5D

Physical limitation -0.49 0.69 0.46

Symptoms -0.50

Quality of life 0.52 0.50 0.52

Social limitation 0.50

Overall summary -0.53

KCCQ, Kansas City Cardiomyopathy Questionnaire; NYHA, New York Heart Association; SF-12, Medical Outcomes Study Short-Form 12; PCS, physical components summary; MCS, mental components summary; 6MWT, 6-minute walk test

P<0.0001 for all correlations



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Figure Legends

Figure 1. A. Mean scores on the KCCQ Symptom Scale according to baseline NYHA

classification. B. Mean scores on the KCCQ Overall Summary Scale by baseline NYHA

classification. KCCQ, Kansas City Cardiomyopathy Questionnaire; NYHA, New York Heart

Association

Figure 2. Kaplan-Meier survival curves according to baseline scores on the KCCQ Overall

Summary Scale among medically-managed patients (n=157). KCCQ, Kansas City

Cardiomyopathy Questionnaire



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Leon, Craig R. Smith, Matthew R. Reynolds, John G. Webb, Lars G. Svensson and David J. CohenSuzanne V. Arnold, John A. Spertus, Yang Lei, Keith B. Allen, Adnan K. Chhatriwalla, Martin B.

Patients with Aortic StenosisUtility of the Kansas City Cardiomyopathy Questionnaire for Monitoring Health Status in

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SUPPLEMENTAL MATERIAL Supplemental Table I. Components of the Society for Thoracic Surgeons Mortality Risk Score

Demographics

Age

Sex

Risk Factors

Weight

Height

Diabetes

Diabetes Treatment

Creatinine

Dialysis

Hypertension

Infective Endocarditis

Chronic Lung Disease

Immunosuppression

Peripheral Artery Disease

Previous Interventions

Prior Bypass Surgery

Prior Valve Surgery

Number of Prior Cardiac Surgeries

Preoperative Cardiac Status

Prior Myocardial Infarction

Congestive Heart Failure

New York Heart Association Heart Failure Class

Angina

Cardiogenic Shock

Resuscitation

Arrhythmias

Inotropes

Intra-aortic Balloon Pump

Left Main Disease

Left Ventricular Ejection Fraction

Mitral Stenosis

Status of the Procedure (Elective, Urgent, Emergent)

Supplemental Table II. Baseline Demographic and Clinical Characteristics of the Different Analytic Populations

Characteristic Reliability

n=159 Responsiveness

n=419

Sensitivity to Change n=761

Construct Validity n=739

Prognostic n=157

Age (y) 83.7 ± 7.1 83.4 ± 7.6 83.4 ± 7.5 83.6 ± 7.3 82.9 ± 8.7

Female 46.7% 46.5% 46.1% 46.1% 51.6%

Caucasian 96.1% 93.1% 92.9% 92.0% 91.7%

STS Mortality Risk Score (%) 11.0 ± 3.8 11.5 ± 4.3 11.5 ± 4.1 11.4 ± 3.9 11.8 ± 4.9

Aortic Valve Area (cm2) 0.65 ± 0.19 0.66 ± 0.19 0.65 ± 0.20 0.65 ± 0.19 0.64 ± 0.21

Mean Gradient (mmHg) 45.6 ± 14.5 43.9 ± 15.0 43.6 ± 15.1 44.1 ± 14.9 42.9 ± 15.5

Ejection Fraction (%) 53.0 ± 13.9 53.3 ± 13.9 52.8 ± 14.1 52.9 ± 13.8 49.5 ± 15.2

Prior Myocardial Infarction 23.2% 24.7% 26.6% 26.0% 26.8%

Prior Bypass Graft Surgery 38.8% 39.9% 43.6% 43.3% 43.9%

Oxygen-Dependent Lung Disease 7.9% 12.4% 12.5% 12.2% 26.1%

Creatinine >2mg/dL 14.5% 18.7% 18.6% 17.2% 19.2%

NYHA Class

II 5.9% 7.2% 6.4% 7.2% 5.7%

III 42.8% 44.4% 44.0% 45.3% 49.7%

IV 51.3% 48.4% 49.5% 47.5% 44.6%

Treatment

Medical Management 16.2% 14.7% 100.0%

Surgical Valve Replacement 28.8% 30.0%

Transcatheter Valve Replacement 100.0% 100.0% 55.1% 55.2%

STS, Society of Thoracic Surgeons

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