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ABSTRACT
Background: Improvement in health-related quality of life is a key Cronbach α coefficients showed high internal consistency reliability.
therapeutic goal of disease management in atrial fibrillation (AF). Test–retest reliability of individual items in stable patients (n¼ 33)
Objectives: To describe the development of the AFImpact, an AF- was satisfactory, with intraclass correlation coefficients ranging from
specific health-related quality-of-life patient-reported outcome meas- 0.61 to 0.86. All three AFImpact domain scores differentiated patients
ure. Methods: Development and validation of the AFImpact com- who reported different levels of overall health, thereby supporting
prised a qualitative stage, consisting of a literature review and known-groups validity. Scores for each item improved after cardio-
concept elicitation interviews (91 patients with AF), item generation, version, with effect sizes ranging from —0.19 to —0.65. Conclusions:
and cognitive debriefing (30 patients with AF), and a quantitative Psychometric evaluations support the reliability and validity of the
stage, consisting of evaluation of the instrument’s psychometric AFImpact as a patient-reported outcome instrument to measure the
properties (313 patients with AF). Preliminary responsiveness to impact of AF, with preliminary results in patients undergoing cardi -
change was assessed in 118 patients undergoing cardioversion. oversion supporting responsiveness to change.
Results: On the basis of the literature review and concept elicitation Keywords: atrial fibrillation, health-related quality of life, patient-
interviews, 75 items were generated. Factor analyses guided a reduc - reported outcome measure, validation.
tion to 18 items. Three domains were confirmed: vitality (7 items),
emotional distress (8 items), and sleep (3 items). The 18-item AFIm- Copyright & 2017, International Society for Pharmacoeconomics and
pact demonstrated high item convergent and discriminant validity. Outcomes Research (ISPOR). Published by Elsevier Inc.
Conflicts of interest: K. S. Coyne is employed by Evidera, which provides consulting and other research services to pharmaceu tical,
device, government, and nongovernment organizations, and has received consultancy fees from AstraZeneca. N. Edvardsson was a
consultant for AstraZeneca at the time the AFImpact was developed. A. Rydén is an employee of AstraZeneca.
* Address correspondence to: Anna Rydén, AstraZeneca Gothenburg, Pepparedsleden 1, Mölndal 43150, Sweden. E-
mail: anna.ryden@astrazeneca.com.
1098-3015$36.00 – see front matter Copyright & 2017, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).
Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.jval.2017.06.005
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psychometrically evaluated on the basis of guidance on PRO validity and comprehension through cognitive interviews with 30
measures published by the US Food and Drug Administration patients with AF (10 with paroxysmal, 10 with persistent, and 10
[9,10]. During the development of the AFSymp, patients were also with permanent AF) in the United States. The draft questionnaire
asked about the impact of their AF on HRQOL, including on was completed in an electronic format by 20 patients and in a
energy levels and activities of daily living [10]. pen–paper format by 10 patients. A seven-point Likert scale was
Improvement in HRQOL is a key therapeutic goal in AF manage- used to provide a wide-enough range of response options to
ment and has been identified as a relevant clinical end point in enable detection of small but important differences in scores [20].
trials of AF therapies [5]. Regulatory guidelines recommend that
symptoms and impacts of diseases or conditions be measured Stage II: Validation of the AFImpact (Quantitative)
using direct reporting from patients themselves and that HRQOL
should be clearly differentiated from the core symptoms of a Item reduction, identification of domains, instrument reliability,
disease [9,11]. There is a concern regarding the use of generic and construct validity
HRQOL measures, because they are deemed not sufficiently sensi- A prospective, observational psychometric evaluation study was
tive or specific to detect changes in AF-specific HRQOL [6]. Several conducted at 32 sites in the United States to evaluate the
AF-specific HRQOL instruments are available [12–17]. Nevertheless, AFImpact, administered as an electronic version [10]. The study
their use is limited by uncertain validity [14–17] and limited recruited patients with paroxysmal, persistent, or permanent AF
generalizability [12,13]. For the Atrial Fibrillation Effect on Quality with symptoms in the past 7 days and consisted of a baseline visit
of Life questionnaire (AFEQT, also known as AF-QoL-18), rigorous (visit 1) and a follow-up visit (visit 2; 14 ± 3 days later). There were
validation analyses were conducted on the preliminary long no investigational interventions. The AFImpact was completed at
version of the PRO; similar analyses still remain to be conducted both visits. Patients also completed the 36-item short form health
on the final condensed version that is being used today [15,17]. The survey (SF-36) [21], the University of Toronto Atrial Fibrillation
HeartQoL was psychometrically evaluated in patients with AF; it Severity Scale (AFSS) [22], and the Medical Outcomes Study (MOS)-
was, however, developed in a broad group of patients with Sleep Scale [23] at visit 1 and the Overall Treatment Effect (OTE)
ischemic heart disease, and its validity specifically in patients with [20] at visit 2. Construct validity of the AFImpact was assessed by
AF remains to be established [16]. The European Heart Rhythm examining the association of AFImpact scores with those of well-
Association score was recommended in European Society of established HRQOL questionnaires (i.e., the generic SF-36, the
Cardiology guidelines for assessing symptoms related to AF on disease-specific AFSS, and the MOS-Sleep Scale that measures
the basis of their impact on daily activity, but it has not been sleep problems), and positive correlations were hypothesized.
validated specifically as an HRQOL instrument [18]. These scores
correlate negatively with HRQOL, although they do not discrim- Preliminary responsiveness
inate sufficiently between patients with no symptoms and those Preliminary responsiveness to change was assessed in a pro-
with mild symptoms (a modified version has been proposed to spective, observational, multicenter study of US patients with AF
improve discrimination) and they have not been assessed by AF who were scheduled to undergo either direct-current or pharma-
subtype [19]. cological cardioversion. Patients completed the AFImpact at
The aim of this article was to describe the development baseline (before cardioversion) and the AFImpact and the OTE
of the AFImpact, an AF-specific PRO measure that was at follow-up (14 ± 2 days after cardioversion).
developed and evaluated in accordance with current regulatory
guidelines.
Statistical Analyses
Item reduction, identification of domains, instrument reliability,
Methods and construct validity
Analyses were conducted using Statistical Analysis System ver-
The AFImpact was developed and validated in two stages: stage I sion 8 (SAS Institute, Cary, NC), Multitrait Analysis Program-
was qualitative and consisted of concept elicitation, item gen- Revised version 1.0 (RAND Corp., Santa Monica, CA), and Rasch
eration, and cognitive interviews; stage II was quantitative and Unidimensional Measurement Models software version 3.1
involved the evaluation of the instrument’s psychometric (RUMM Laboratory, Perth, WA). Item reduction and identification
properties. of domains were informed by using frequency distributions of
response options, exploratory and confirmatory factor analyses
using varimax rotation and oblimin rotation, and Rasch analysis.
Stage I: Development of the AFImpact (Qualitative)
Items were deleted if more than 30% of respondents gave the
Concept elicitation was conducted jointly for the AFImpact and lowest possible score or the highest possible score.
the AFSymp [10]. After conducting a literature review, concepts Cronbach α was used to assess internal consistency
about AF symptoms and impacts were elicited during qualitative reliability. Test–retest reliability (intraclass correlation coeffi-
interviews among 91 patients from the United States, Europe, and cient) was assessed in patients whose status was considered
Japan (n ¼ 30, 46, and 15, respectively) who had a confirmed stable (defined as patients who reported that their health was
diagnosis of paroxysmal, persistent, or permanent AF (n ¼ 30, 30, “the same”: a score of “0” on the OTE at the second study visit).
and 31, respectively). Interviews were conducted by trained Construct validity (convergent and discriminant validity) was
interviewers following a standardized interview guide. During examined by using Pearson correlations between the AFImpact
the interviews, patients were asked to describe the impact of AF domain scores and the SF-36, the MOS-Sleep Scale, and the AFSS
and its treatment on their daily routine, including physical Wellbeing, Total AF Burden, and Total Symptom Severity domain
functioning, emotional well-being, and work. Interviews were scores at visit 1. Known-groups validity was assessed by compar-
transcribed verbatim. Transcripts were analyzed qualitatively to ing AFImpact scores between groups of patients who self-
identify participants’ expressions of concepts. reported different levels of overall health on item 1 of the SF- 36,
After the concept elicitation interviews, draft items for the patients who reported being currently in AF and those who
AFImpact were generated in US English on the basis of an reported not being currently in AF (as reported on item 3 of the
analysis of the qualitative interview information about the AFSS: “Are you in atrial fibrillation currently?”), and patients with
impact of AF. The draft items were then evaluated for content different levels of clinician-reported AF severity (physicians were
VA LU E I N H EA LT H ] (2 0 1 7 ) ]]] – ] ]] 3
* The following ancillary measures were used to assess convergent and discriminant validity: 36 -item short form health survey, University of Toronto Atrial Fibrillation Severity Scale, and
Preliminary responsiveness
Table 1 – Convergent validity, discriminant validity, and internal consistency of items and floor and ceiling analyses of domains of the AFImpact (psychometric
Effect size was calculated as the difference in mean scores (i.e.,
22.0
7.3
7.7
follow-up mean score – baseline mean score) divided by the SD of
the baseline score. Standardized response mean was calculated
as the difference in mean scores (i.e., follow-up mean score –
baseline mean score) divided by the SD of the score change.
Domain analyses
Results
0.6
0.0
0.0
lives and HRQOL. The greatest impact was on patients’ daily
living and physical functioning, primarily in terms of reduced
motility, low vitality, and sleep problems. Emotional well-being
was also considerably affected, with patients feeling anxious and
Proportion of item-domain correlations that were higher with the item’s own domain than with the other AFImpact domains.
worried about their AF. Results were generally similar across
groups. Some subtle variations included that more patients with
paroxysmal AF spoke about depression than those with persis-
tent or permanent AF, and that patients from Europe spoke in
more detail about the impacts of their AF on daily living than did
patients from the United States and Japan. On the basis of these consistency,
interviews, 75 items were generated that included all the HRQOL Cronbach α
Internal
0.90
include all HRQOL concepts patients specifically noted were
impacted by AF. The term “because of my heart condition” was
included in each question instead of “because of my atrial
fibrillation,” because it was found that some patients were not
familiar with the term “atrial fibrillation.”
Of the 30 patients who took part in the cognitive interviews,
Discriminant validity*,
and answer, and 25 agreed that it was clear. A 1-week recall was
supported by half the patients (the other half suggested that this
Item analyses
was too short of a recall and wanted a longer period). The draft
100
100
100
0.77–0.83
‡
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item convergent validity and high item discriminant validity my heart condition”), to 0.86, for item 15 (“I felt depressed
(Table 1). Mean item scores of the AFImpact ranged from 2.5 ± because of my heart condition”) (Table 2).
1.4, for item 15 (“I felt depressed because of my heart condition”),
and 2.5 ± 1.5, for item 9 (“I woke up during the night because of
Domain convergent and discriminant validity
my heart condition”), to 3.2 ± 1.7, for item 17 (“I could not be
We hypothesized that AFImpact domains would correlate pos-
as physically active as I wanted to be because of my heart
itively with SF-36 and AFSS domains, which measure similar
condition”).
concepts, and the MOS-Sleep Scale. Correlations between the
AFImpact domains and the AFSS Wellbeing, Total AF Burden, and
Total Symptom Severity domains were statistically significant (r,
range —0.48 to 0.70; all P o 0.0001). Correlations between the
Reliability
AFImpact domains and the SF-36 domains were statistically
Cronbach α coefficients demonstrated high internal consistency
significant (all r 4 0.40; all P o 0.0001), with domains measuring
reliability (Table 1). Domain analyses showed no floor effects for
similar concepts correlating more highly (convergent validity)
any of the three domains and no ceiling effects for the vitality
than those measuring dissimilar concepts (discriminant validity).
and the emotional distress domains. There was, however, a
The AFImpact sleep domain correlated with the MOS-Sleep Scale
ceiling effect for the three-item sleep domain, with 22% of
domains and composite scores (r, range —0.22 to 0.78; all P o
patients scoring the highest possible score (Table 1).
0.005), further supporting convergent validity.
Interscale correlations (r) were 0.71, 0.64, and 0.70 for vitality
versus emotional distress, emotional distress versus sleep, and
sleep versus vitality, respectively, indicating that the three Known-groups validity
domains measure related concepts but are not so highly corre- All three AFImpact domain scores differentiated between
lated as to indicate redundancy. Construct validity findings in patients who reported different levels of overall health on item
patient subgroups with paroxysmal, persistent, or permanent AF 1 of the SF-36 (all P o 0.0001), with a clear pattern of lower scores
were similar to those in the overall study population (data not for patients reporting better general health (Fig. 1). For all three
shown). domains, scores were significantly higher for patients who
In total, 152 of the patients who took part in the psychometric reported being currently in AF than for patients who reported
evaluation study had a follow-up visit within 11 to 17 days after not being currently in AF (Fig. 2), providing further evidence of
their baseline visit, of whom 111 reported that their health was the known-groups validity.
about the same (OTE score —1, 0, or 1) and 33 reported that their The AFImpact domain scores also differentiated between
health was the same (OTE score 0). Test–retest reliability of the different levels of clinician-reported AF severity (all P o 0.0001).
AFImpact individual items in stable patients (n ¼ 33; defined by The severity of AF symptoms was reported by physicians as very
OTE score 0) was satisfactory, with intraclass correlation coef- mild, mild, moderate, and severe for 12.8%, 47.3%, 36.1%, and
ficients ranging from 0.61, for item 12 (“I felt worn out because of 3.8% of patients, respectively. Mean scores for each of these four
Table 2 – Test–retest reliability in stable patients between visit 1 and visit 2 in the psychometric evaluation
study (n ¼ 33).
Item Item score, mean ± SD t value P value Spearman r‡ ICC
1. Did not sleep well 3.1 ± 1.6 3.2 ± 1.9 0.0 0.12 0.9035 0.66§ 0.66
2. Worried might shorten my life 3.3 ± 1.9 3.1 ± 1.9 —0.2 —1.04 0.3039 0.77§ 0.81
3. Felt anxious 3.5 ± 1.8 3.1 ± 1.9 —0.4 —1.51 0.1421 0.65§ 0.71
4. Less energy 3.4 ± 1.5 3.4 ± 1.7 0.0 —0.14 0.8890 0.67§ 0.72
5. Annoyed 2.7 ± 1.9 2.7 ± 1.8 0.0 0.00 1.0000 0.77§ 0.85
6. Stressed 3.3 ± 1.8 3.1 ± 1.9 —0.2 —0.94 0.3531 0.71§ 0.75
7. Walk slowly 3.3 ± 1.8 3.1 ± 1.9 —0.2 —0.86 0.3947 0.75§ 0.79
8. Tired 3.2 ± 1.7 3.4 ± 1.6 0.2 1.14 0.2632 0.81§ 0.85
9. Woke up during the night 3.1 ± 1.7 3.0 ± 1.7 —0.1 —0.27 0.7902 0.69§ 0.72
10. Performed daily activities slowly 3.1 ± 1.7 3.1 ± 2.0 —0.1 —0.24 0.8126 0.63§ 0.69
11. Worried about my health 3.2 ± 2.0 2.8 ± 1.8 —0.4 —1.74 0.0908 0.74§ 0.76
12. Felt worn out 3.2 ± 1.6 3.2 ± 1.8 0.0 0.12 0.9089 0.56§ 0.61
13. Difficulty falling asleep 3.0 ± 1.7 3.4 ± 1.9 0.4 1.45 0.1566 0.64§ 0.62
14. Nervous 3.1 ± 1.9 2.8 ± 1.8 —0.2 —0.88 0.3860 0.65§ 0.72
15. Depressed 2.7 ± 1.6 2.4 ± 1.8 —0.3 —1.79 0.0831 0.86§ 0.86
16. Had to rest during the day 3.3 ± 1.7 3.3 ± 1.8 0.0 0.12 0.9089 0.55§ 0.64
17. Not as physically active 3.5 ± 1.9 3.4 ± 1.9 —0.1 —0.49 0.6245 0.73§ 0.73
18. Worried might get worse 3.3 ± 1.8 3.2 ± 1.7 —0.1 —0.30 0.7628 0.72§ 0.79
Note. The evaluation was done in 33 stable patients, defined as having a score of 0 (“about the same”) on the OTE.
ICC, intraclass correlation coefficient; OTE, Overall Treatment Effect.
* Window of 11–14 d.
†
Visit 2 mean score minus visit 1 mean score. Note. Values do not always equal the difference between the values presented in the 'Visit 1'
and 'Visit 2' columns because of rounding.
‡
Spearman rank-order correlations.
§
P o 0.001.
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Table 3 – Change in domains and item scores from baseline to follow-up in patients undergoing cardioversion
(N ¼ 118).
Domain/item Item score, mean ± SD P value‡ Effect size§ Standard
response mean||
Baseline Follow-up* Difference†
Domain
Vitality 3.1 ± 1.5 2.5 ± 1.4 —0.6 ± 1.3 o0.0001 —0.41 —0.50
Emotional distress 3.9 ± 1.8 3.0 ± 1.7 —1.0 ± 1.5 o0.0001 —0.53 —0.62
Sleep 2.6 ± 1.5 1.9 ± 1.2 —0.7 ± 1.3 o0.0001 —0.45 —0.51
Item
1. Did not sleep well 2.7 ± 1.7 1.9 ± 1.3 —0.8 ± 1.6 o0.0001 —0.45 —0.49
2. Worried might shorten my life 3.0 ± 1.8 2.4 ± 1.6 —0.6 ± 1.7 0.0002 —0.33 —0.35
3. Felt anxious 3.1 ± 1.7 2.5 ± 1.6 —0.6 ± 1.7 o0.0001 —0.38 —0.38
4. Less energy 4.5 ± 2.0 3.2 ± 2.0 —1.3 ± 1.9 o0.0001 —0.65 —0.68
5. Annoyed 3.5 ± 2.1 2.7 ± 1.8 —0.8 ± 1.9 o0.0001 —0.37 —0.40
6. Stressed 3.3 ± 1.8 2.5 ± 1.6 —0.8 ± 1.6 o0.0001 —0.43 —0.49
7. Walk slowly 3.5 ± 2.2 2.7 ± 1.9 —0.8 ± 1.8 o0.0001 —0.38 —0.47
8. Tired 4.3 ± 2.0 3.1 ± 1.9 —1.2 ± 1.7 o0.0001 —0.62 —0.69
9. Woke up during the night 2.6 ± 1.8 1.8 ± 1.4 —0.8 ± 1.8 o0.0001 —0.42 —0.42
10. Performed daily activities slowly 3.6 ± 2.1 2.8 ± 1.9 —0.9 ± 1.9 o0.0001 —0.41 —0.45
11. Worried about my health 3.3 ± 1.8 2.7 ± 1.7 —0.6 ± 1.7 0.0003 —0.32 —0.34
12. Felt worn out 3.9 ± 2.0 3.0 ± 2.0 —0.9 ± 2.0 o0.0001 —0.44 —0.43
13. Difficulty falling asleep 2.4 ± 1.6 1.9 ± 1.4 —0.5 ± 1.5 0.0003 —0.32 —0.35
14. Nervous 3.0 ± 1.7 2.3 ± 1.6 —0.7 ± 1.5 o0.0001 —0.43 —0.49
15. Depressed 2.4 ± 1.7 2.1 ± 1.5 —0.3 ± 1.5 0.0284 —0.19 —0.21
16. Had to rest during the day 3.4 ± 1.9 2.7 ± 1.8 —0.7 ± 1.8 o0.0001 —0.38 —0.40
17. Not as physically active 4.2 ± 2.2 3.3 ± 2.1 —0.9 ± 2.0 o0.0001 —0.41 —0.45
18. Worried might get worse 3.5 ± 1.9 2.8 ± 1.8 —0.7 ± 1.5 o0.0001 —0.35 —0.44
* Window of 2 wk ± 2 d.
†
Follow-up mean score minus baseline mean score. Note. Values do not always equal the difference between the values presented in the
‘Baseline’ and ‘Follow-up’ columns because of rounding.
‡
Matched t test.
§
Difference in mean scores±i.e., follow-up mean score – baseline mean score) divided by the SD of the baseline score.
||
Difference in mean scores±i.e., follow-up mean score – baseline mean score) divided by the SD of the score change.
their not being recommended as a primary outcome measure in cross-cultural patient input, the quantitative development and
clinical trials in the last decade [26]. psychometric evaluation were conducted in the United States
Another potential reason for HRQOL measures traditionally and still need cross-cultural validation. Also, the assessments of
not being used as primary end points is that trials of interven- its responsiveness to change are based on preliminary data and
tions for AF, both pharmacological and nonpharmacological, require confirmation. Furthermore, some patients may have
have focused much on measuring the effect on AF per se, such found it difficult to respond to item 3 of the AFSS, about whether
as time to first recurrence, AF burden, and progression from they were currently in AF. Last, the 1-week recall of the AFImpact
paroxysmal to persistent or permanent AF, and on correlating the has potential drawbacks for patients who experience impacts of
results to the risk of stroke or other outcomes. Nevertheless, AF less frequently than weekly.
it seems sensible to use the effects on symptoms and the
impact of symptoms on HRQOL as a patient end point, because
symptoms are a major reason why patients with AF seek care [3]. Conclusions
This approach will become more feasible with the availability of
The AFImpact was developed with patient input and in accordance
an AF-specific instrument developed to regulatory guidelines and
with current regulatory guidelines. Psychometric evaluations sup-
when trials are designed to detect a difference in severity of
port the reliability and validity of the AFImpact as a PRO instru-
symptoms as well as to assess the effect on symptom-related
ment to measure the impact of AF, with preliminary results in
HRQOL between a new treatment and placebo/no treatment or a
patients undergoing cardioversion supporting the instrument’s
comparator treatment. AF is a long-term, chronic condition that
responsiveness to change.
is generally symptomatic and it is thus useful to include a PRO to
monitor patient status over time. In future, AF-specific HRQOL
assessment may become a more important measure when differ- Acknowledgments
entiating between treatments in clinical trials or considering
patient preferences for therapy options in clinical practice. We thank Jennie Medin and Karoly Kulich for their contributions
The development and psychometric evaluation of the AFIm- to the study.
pact support its reliability and validity. Nevertheless, although Source of financial support: This study was funded by Astra-
the qualitative development of the questionnaire was based on Zeneca Gothenburg (Mölndal, Sweden). Writing support was
VA LU E I N H EA LT H ] (2 0 1 7 ) ]]] – ] ]] 7
provided by Dr Anja Becher from Oxford PharmaGenesis Ltd Evaluation of Medicinal Products. London: Committee for Medicinal
(Oxford, UK) and was funded by AstraZeneca Gothenburg Products for Human Use of the European Medicines Agency, 2005.
[12] Arribas F, Ormaetxe JM, Peinado R, et al. Validation of the AF-QoL, a
(Mölndal, Sweden).
disease-specific quality of life questionnaire for patients with atrial
fibrillation. Europace 2010;12:364–70.
[13] Badia X, Arribas F, Ormaetxe JM, et al. Development of a questionnaire
R EF ER ENCES to measure health-related quality of life (HRQoL) in patients with atrial
fibrillation (AF-QoL). Health Qual Life Outcomes 2007;5:37.
[14] Braganca EO, Filho BL, Maria VH, et al. Validating a new quality of life
questionnaire for atrial fibrillation patients. Int J Cardiol 2010;143:391–8.
[1] Chugh SS, Roth GA, Gillum RF, Mensah GA. Global burden of atrial [15] Dorian P, Burk C, Mullin CM, et al. Interpreting changes in quality of life
fibrillation in developed and developing nations. Glob Heart in atrial fibrillation: How much change is meaningful? Am Heart J
2014;9:113–9. 2013;166:381–7.
[2] Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology [16] Kristensen MS, Zwisler AD, Berg SK, et al. Validating the HeartQoL
of atrial fibrillation: European perspective. Clin Epidemiol questionnaire in patients with atrial fibrillation. Eur J Prev Cardiol
2014;6:213–20. 2016;23:1496–503.
[3] Rienstra M, Lubitz SA, Mahida S, et al. Symptoms and functional status [17] Spertus J, Dorian P, Bubien R, et al. Development and validation of the
of patients with atrial fibrillation: state of the art and future research Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) Questionnaire in
opportunities. Circulation 2012;125:2933–43. patients with atrial fibrillation. Circ Arrhythm Electrophysiol 2011;4:15–25.
[4] Nabauer M, Gerth A, Limbourg T, et al. The Registry of the German [18] Camm AJ, Kirchhof P, Lip GY, et al. Guidelines for the management of
Competence NETwork on Atrial Fibrillation: patient characteristics and atrial fibrillation: the Task Force for the Management of Atrial Fibrillation
initial management. Europace 2009;11:423–34. of the European Society of Cardiology (ESC). Europace 2010;12:1360–420.
[5] Savelieva I, Kirchhof P, Danchin N, et al. Regulatory pathways for [19] Wynn GJ, Todd DM, Webber M, et al. The European Heart Rhythm
development of antiarrhythmic drugs for management of atrial Association symptom classification for atrial fibrillation: validation and
fibrillation/flutter. Europace 2011;13:1063–76. improvement through a simple modification. Europace 2014;16:965–72.
[6] Calkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS Expert [20] Jaeschke R, Singer J, Guyatt GH. Measurement of health status:
Consensus Statement on Catheter and Surgical Ablation of Atrial ascertaining the minimal clinically important difference. Control Clin
Fibrillation: recommendations for patient selection, procedural Trials 1989;10:407–15.
techniques, patient management and follow-up, definitions, endpoints, [21] Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey
and research trial design. Europace 2012;14:528–606. (SF-36), I: conceptual framework and item selection. Med Care
[7] Peinado R, Arribas F, Ormaetxe JM, Badia X. Variation in quality of life 1992;30:473–83.
with type of atrial fibrillation. Rev Esp Cardiol 2010;63:1402–9. [22] Dorian P, Jung W, Newman D, et al. The impairment of health-related
[8] January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the quality of life in patients with intermittent atrial fibrillation:
management of patients with atrial fibrillation: a report of the American implications for the assessment of investigational therapy. J Am Coll
College of Cardiology/American Heart Association Task Force on Practice Cardiol 2000;36:1303–9.
Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014;64:e1–76. [23] Hays RD, Stewart AL. Sleep measures. In: Stewart AL, Ware JEJ, eds.
[9] US Food and Drug Administration. Guidance for Industry. Patient- Measuring Functioning and Well-Being: The Medical Outcomes Study
Reported Outcome Measures: Use in Medical Product Development to Approach. Durham, NC: Duke University Press, 1992. p. 235–59.
Support Labeling Claims. Rockville, MD: US Food and Drug [24] Mark DB. Assessing quality-of-life outcomes in cardiovascular clinical
Administration, 2009. research. Nat Rev Cardiol 2016;13:286–308.
[10] Medin J, Arbuckle R, Abetz L, et al. Development and validation of the [25] Moreira RS, Bassolli L, Coutinho E, et al. Reproducibility and reliability
AFSymp: an atrial fibrillation-specific measure of patient-reported of the Quality of Life Questionnaire in patients with atrial fibrillation.
symptoms. Patient 2014;7:319–27. Arq Bras Cardiol 2016;106:171–81.
[11] European Medicines Agency. Reflection Paper on the Regulatory Guidance [26] Kirchhof P, Auricchio A, Bax J, et al. Outcome parameters for trials in
for the Use of Health-Related Quality of Life (HRQL) Measures in the atrial fibrillation: executive summary. Eur Heart J 2007;28:2803–17.