Multinational and multiethnic variations in health-related quality of life in patients with chronic heart failure

doi:10.1016/j.ahj.2017.06.016

American Heart Journal

Volume 191, September 2017, Pages 75-81

https://doi.org/10.1016/j.ahj.2017.06.016 Get rights and content

Background

Assessing health-related quality of life (HRQoL) in patients with heart failure (HF) is an important goal of clinical care and HF research. We sought to investigate ethnic differences in perceived HRQoL and its association with mortality among patients with HF and left ventricular ejection fraction ≤35%, controlling for demographic characteristics and HF severity.

Methods and results

We compared 5697 chronic HF patients of Indian (26%), white (23%), Chinese (17%), Japanese/Koreans (12%), black (12%), and Malay (10%) ethnicities from the HF-ACTION and ASIAN-HF multinational studies using the Kansas City Cardiomyopathy Questionnaire (KCCQ; range 0-100; higher scores reflect better health status). KCCQ scores were lowest in Malay (58 ± 22) and Chinese (60 ± 23), intermediate in black (64 ± 21) and Indian (65 ± 23), and highest in white (67 ± 20) and Japanese or Korean patients (67 ± 22) after adjusting for age, sex, educational status, HF severity, and risk factors. Self-efficacy, which measures confidence in the ability to manage symptoms, was lower in all Asian ethnicities (especially Japanese/Koreans [60 ± 26], Malay [66 ± 23], and Chinese [64 ± 28]) compared to black (80 ± 21) and white (82 ± 19) patients, even after multivariable adjustment (P < .001). In all ethnicities, KCCQ strongly predicted 1-year mortality (HR 0.45, 95% CI 0.30-0.67 for highest vs lowest quintile of KCCQ; P for interaction by ethnicity .101).

Conclusions

Overall, HRQoL is inversely and independently related to mortality in chronic HF but is not modified by ethnicity. Nevertheless, ethnic differences exist independent of HF severity and comorbidities. These data may have important implications for future global clinical HF trials that use patient-reported outcomes as endpoints.

Section snippets

Methods

For the current analysis, we combined the participants from HF-ACTION (N = 1998) and the ASIAN-HF registry (N = 3699) with left ventricular ejection fraction (EF) ≤35% to form a combined cohort of 5697 patients. The trial design and results of HF-ACTION have been previously reported.12., 13. This multicenter, randomized controlled trial compared the long-term safety and efficacy of exercise training plus evidence-based HF medical therapy versus medical therapy alone in patients with HFrEF (EF ≤35%)

Results

In the combined cohort of 5697 participants, the median age was 60 (IQR 51-68) years, and 24% were women; baseline characteristics of the cohort by ethnicity are shown in Table II. In general, disease characteristics and comorbidities varied among the ethnic groups. Black or African American (median age 55) and Malay participants (median age 56) were the youngest, while white (median age 62) and Japanese/Korean (median age 67) participants were the oldest. Malay participants had the highest

Discussion

To our knowledge, these data represent the largest analysis of cross-continental ethnic differences in HRQoL among patients with chronic HF. Despite acknowledgement of the large and growing global public health burden of HF, substantial knowledge and care gaps exist, especially among low- and middle-income regions of Asia, where resources are particularly limited.23., 24. In this study, we show that—independent of clinical covariates—HRQoL as defined by the patient's KCCQ score is significantly

Disclosures

The authors report no relevant disclosures.

Acknowledgements

We thank all investigators and participants of HF-ACTION and ASIAN-HF for their contribution.

References (33)

A.A. Kelkar et al.
Utility of Patient-Reported Outcome Instruments in Heart Failure
JACC Heart Fail
(2016)
C.P. Green et al.
Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure
J Am Coll Cardiol
(2000)
P.A. Heidenreich et al.
Health status identifies heart failure outpatients at risk for hospitalization or death
J Am Coll Cardiol
(2006)
D.J. Whellan et al.
Heart failure and a controlled trial investigating outcomes of exercise training (HF-ACTION): design and rationale
Am Heart J
(2007)
J. Comin-Colet et al.
Validation of the Spanish version of the Kansas city cardiomyopathy questionnaire
Rev Esp Cardiol
(2011)
R.J. Mentz et al.
Heart failure clinical trials in East and Southeast Asia: understanding the importance and defining the next steps
JACC Heart Fail
(2016)
F. Qian et al.
Racial differences in heart failure outcomes: evidence from the Tele-HF Trial (Telemonitoring to Improve Heart Failure Outcomes)
JACC Heart Fail
(2015)
W.T. Abraham et al.
Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial
Lancet
(2011)
T. Jaarsma et al.
Self-care and quality of life in patients with advanced heart failure: the effect of a supportive educational intervention
Heart Lung
(2000)
J. Spertus et al.
Monitoring clinical changes in patients with heart failure: a comparison of methods
Am Heart J
(2005)

J.M. Peppercorn et al.

Comparison of outcomes in cancer patients treated within and outside clinical trials: conceptual framework and structured review

Lancet

(2004)

M.A. Konstam et al.

Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial

JAMA

(2007)

K.E. Flynn et al.

Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial

JAMA

(2009)

Food Drug Administration Center for Drugs Evaluation Research

Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims

(2009)

I.B. Wilson et al.

Linking clinical variables with health-related quality of life. A conceptual model of patient outcomes

JAMA

(1995)

K.I. Pettersen et al.

Reliability and validity of the Kansas City cardiomyopathy questionnaire in patients with previous myocardial infarction

Eur J Heart Fail

(2005)

Cited by (32)

The Effectiveness of Lifestyle Interventions in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Network Meta-Analysis
2024, Journal of Cardiac Failure
To perform a network meta-analysis to determine the effectiveness of lifestyle interventions in exercise tolerance and quality of life (QoL) in people with HFpEF.
Ten databases were searched for randomized controlled trials that evaluated a diet and/or exercise intervention in people with heart failure with preserved ejection fraction until May 2022. The co-primary outcomes were peak oxygen uptake (V̇O_2peak) and Quality of Life as assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). We synthesized data using network meta-analysis.
We identified 13 trials, including a total of 869 participants, and we incorporated 6 different interventions. Improvements in V̇O_2peak compared to controls were seen for all exercise interventions (2.88 [95% CI: 1.36; 4.39] mL/kg/min) for high-intensity interval training (HIIT); 2.37 [95% CI: 1.02; 3.71] mL/kg/min for low-intensity exercise (LIT) combined with a hypocaloric diet; 2.05 [95% CI: 0.81; 3.29] mL/kg/min for moderate-intensity continuous training (MICT); 1.94 [95% CI: 0.59; 3.29] mL/kg/min for LIT; 1.85 [95% CI: 0.27; 3.44] mL/kg/min for MICT combined with resistance training) but not a hypocaloric diet alone (1.26 [95%CI: -0.08; 2.61] mL/kg/min). Only HIIT (-14.45 [95%CI: -24.81; -4.10] points) and LIT (95% CI: -11.05 [-20.55; -1.54] mL/kg/min) significantly improved MLHFQ scores. Network meta-analysis indicated that HIIT was the most effective intervention for improving both V̇O_2peak (mean improvement 2.88 [95% CI: 1.36; 4.39] mL/kg/min, follow-up range, 4 weeks–3 years) and QoL (-14.45 [95% CI: -24.81; -4.10] points, follow-up range, 12–26 weeks) compared to usual care.
This network meta-analysis indicates that HIIT is the most effective lifestyle intervention studied to improve exercise capacity and QoL, with mean improvements exceeding the minimum clinically meaningful thresholds. HIIT is likely to be an underused management strategy in HFpEF, but further studies are needed to confirm long-term improvements in symptoms and clinical outcomes.
Changes in health-related quality of life and treatment effects in chronic heart failure: a meta-analysis
2023, International Journal of Cardiology
Heart failure (HF) is associated with poor health status, and high morbi-mortality. However, it is not well established how health status changes correlate with treatment effects on clinical outcomes. Our aim was to study the association between treatment-induced changes in health-status, assessed by Kansas City Cardiomyopathy Questionnaire 23 (KCCQ-23), and clinical outcomes in chronic HF.
Systematic search of phase III-IV pharmacological RCTs in chronic HF that assessed KCCQ-23 changes and clinical outcomes throughout follow-up. We studied the association between treatment induced changes in KCCQ-23 and treatment effects on clinical outcomes (HF hospitalization or cardiovascular death, HF hospitalization, cardiovascular death, and all-cause death) using weighted random-effects meta-regression.
Sixteen trials were included, enrolling a total of 65,608 participants. Treatment induced KCCQ-23 changes were moderately correlated with treatment effects on the combined outcome of HF hospitalization or cardiovascular mortality (regression coefficient (RC) = −0.047, 95%CI: −0.085 to −0.009; R² = 49%), a correlation that was mainly driven by HF hospitalization (RC = −0.076, 95%CI: −0.124 to −0.029; R² = 56%). Correlations of treatment induced KCCQ-23 changes with cardiovascular death (RC = −0.029, 95%CI: −0.073 to 0.015; R² = 10%) and all-cause death (RC = −0.019, 95%CI: −0.057 to 0.019; R² = 0%) were weak and non-significant.
Treatment-induced changes in KCCQ-23 were moderately correlated with treatment-effects on HF hospitalizations but were not correlated with the effects on cardiovascular and all-cause mortality. Treatment-induced changes in patient-centered outcomes (i.e., KCCQ-23) may reflect non-fatal symptomatic changes in the clinical course of HF leading to hospitalization.
Patient-Reported Status and Heart Failure Outcomes in Asia by Sex, Ethnicity, and Socioeconomic Status
2023, JACC: Asia
In heart failure (HF), symptoms and health-related quality of life (HRQoL) are known to vary among different HF subgroups, but evidence on the association between changing HRQoL and outcomes has not been evaluated.
The authors sought to investigate the relationship between changing symptoms, signs, and HRQoL and outcomes by sex, ethnicity, and socioeconomic status (SES).
Using the ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) Registry, we investigated associations between the 6-month change in a “global” symptoms and signs score (GSSS), Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS), and visual analogue scale (VAS) and 1-year mortality or HF hospitalization.
In 6,549 patients (mean age: 62 ± 13 years], 29% female, 27% HF with preserved ejection fraction), women and those in low SES groups had higher symptom burden but lower signs and similar KCCQ-OS to their respective counterparts. Malay patients had the highest GSSS (3.9) and lowest KCCQ-OS (58.5), and Thai/Filipino/others (2.6) and Chinese patients (2.7) had the lowest GSSS scores and the highest KCCQ-OS (73.1 and 74.6, respectively). Compared to no change, worsening of GSSS (>1-point increase), KCCQ-OS (≥10-point decrease) and VAS (>1-point decrease) were associated with higher risk of HF admission/death (adjusted HR: 2.95 [95% CI: 2.14-4.06], 1.93 [95% CI: 1.26-2.94], and 2.30 [95% CI: 1.51-3.52], respectively). Conversely, the same degrees of improvement in GSSS, KCCQ-OS, and VAS were associated with reduced rates (HR: 0.35 [95% CI: 0.25-0.49], 0.25 [95% CI: 0.16-0.40], and 0.64 [95% CI: 0.40-1.00], respectively). Results were consistent across all sex, ethnicity, and SES groups (interaction P > 0.05).
Serial measures of patient-reported symptoms and HRQoL are significant and consistent predictors of outcomes among different groups with HF and provide the potential for a patient-centered and pragmatic approach to risk stratification.
Functional and Symptomatic Clinical Trial Endpoints: The HFC-ARC Scientific Expert Panel
2022, JACC: Heart Failure
Citation Excerpt :
Consensus Recommendations The KCCQ and MLHFQ are established symptomatic endpoint assessments, but further data are needed to ensure their consistent acquisition and interpretation among diverse patient groups.24 Remote PRO capture should use standardized and validated processes to minimize exclusions (such as for non–English speakers and nonreaders), variability (such as by participation by caregivers and differences in environmental or external stressors), and missing data across trials and modalities.
The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and the Academic Research Consortium (ARC) composed of patients, academic investigators from the United States and Europe, the U.S. Food and Drug Administration, the National Institutes of Health, payers, and industry. Members discussed the measure, remote capture, and clinical utility of functional and quality-of-life endpoints for use in clinical trials of heart failure and cardiovascular therapeutics, with the goal of improving the efficiency of heart failure and cardiovascular clinical research, evidence generation, and thereby patient quality of life, functional status, and survival. Assessments of patient-reported outcomes and maximal and submaximal exercise tolerance are standardized and validated, but actigraphy remains inconsistent as a potential endpoint. This paper details those discussions and consensus recommendations.
Prevalence and Prognostic Significance of Frailty in Asian Patients With Heart Failure: Insights From ASIAN-HF
2021, JACC: Asia
Citation Excerpt :
The assessment of health-related quality of life in patients with HF was measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a 23-item self-administered HF-specific questionnaire validated in multiple HF-related disease states (22-24). This instrument has been widely used in recent international HF clinical trials and has been validated in several languages (19). The KCCQ is the most sensitive surrogate measure to capture such patients' health status.
Frailty is common in patients with heart failure (HF) and can adversely impact outcomes.
This study examined the prevalence of frailty among Asian patients with HF, its association with 1-year outcomes, and if race-ethnicity, HF subtypes, and sex modify this relationship.
In the multinational ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, a baseline frailty index (FI) was constructed using a cumulative deficits approach with 48 baseline variables, and patients were followed for the 1-year primary outcome of all-cause death or HF hospitalization.
Among 3,881 participants (age 61 ± 13 years, 27% female), the mean FI was 0.28 ± 0.11, and 69% were frail (FI >0.21). Higher FI was associated with older age, Malay ethnicity, and Southeast Asian residency. While comorbidities were more frequent in frail patients (by definition), body mass index was not different across frailty classes. Compared with FI class 1 (<0.21, nonfrail), FI class 2 (0.21-0.31) and FI class 3 (>0.31) had increased risk of the 1-year composite outcome (hazard ratios of 1.84 [95% confidence interval (CI): 1.42-2.38] and 4.51 [95% CI: 3.59-5.67], respectively), even after multivariable adjustment (adjusted hazard ratios of 1.49 [95% CI: 1.13-1.97] and 2.69 [95% CI: 2.06-3.50], respectively). Race-ethnicity modified the association of frailty with the composite outcome (P_interaction = 0.0097), wherein the impact of frailty was strongest among Chinese patients. The association between frailty and outcomes did not differ between men and women (P_interaction = 0.186) or for HF with reduced ejection fraction versus HF with preserved ejection fraction (P_interaction = 0.094).
Most Asian patients with HF are frail despite relatively young age. Our results reveal specific ethnic (Malay) and regional (Southeast Asia) predisposition to frailty and highlight its prognostic importance, especially in Chinese individuals. (ASIAN HF Registry, A Prospective Observational Study [ASIANHF]; NCT01633398)
Health-Related Quality of Life in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial
2019, JACC: Heart Failure
Citation Excerpt :
In addition to English, KCCQ has been validated in Swedish, Italian, German, Portuguese, Spanish, Norwegian, and Mandarin in peer-reviewed publications (24). The KCCQ has also been used in assessing HRQL among Japanese, Korean, and Hindi languages (25). The KCCQ was administered at randomization to 4,735 (98%) patients.
This study sought to describe baseline health-related quality of life (HRQL) in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, the largest heart failure with preserved ejection fraction (HFpEF) trial to date.
There are limited data characterizing HRQL in patients with HFpEF using validated metrics.
The PARAGON-HF trial randomized symptomatic patients with HFpEF (≥45%) ≥50 years of age to either sacubitril/valsartan or valsartan. The study reports comprehensive baseline HRQL using Kansas City Cardiomyopathy Questionnaire (KCCQ) administered at randomization after active run-in period. The study then compares baseline HRQL with patients with heart failure with reduced ejection fraction (HFrEF) (≤40%) enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Forward multivariable stepwise regression modeling was performed separately in both trials to identify independent clinical correlates of KCCQ-Overall Summary (KCCQ-OS) score. PARADIGM-HF trial patients <50 years of age were excluded to enable comparison.
In the PARAGON-HF trial, 4,735 of 4,822 patients (mean age 73 ± 8 years; 48% men) completed baseline KCCQ at randomization. Mean KCCQ-OS score was 71. Women had worse mean KCCQ-OS score than men did. Patients in the PARAGON-HF trial reported lower KCCQ scores in nearly all domains when compared with the PARADIGM-HF trial (KCCQ-OS score 71 ± 19 vs. 73 ± 19; p < 0.001). The strongest independent clinical correlates of adverse HRQL in both the PARAGON-HF and PARADIGM-HF trials were New York Heart Association functional class, female gender, lower extremity edema, body mass index, angina, dyspnea, and paroxysmal nocturnal dyspnea. After accounting for these clinical correlates of adverse HRQL that were common to both HFpEF and HFrEF patients, KCCQ-OS score did not differ significantly.
HRQL was largely worse in women and was similar in HFpEF and HFrEF after accounting for variation in demographics, functional status, and symptom burden. (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF [PARAGON-HF] NCT01920711; Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255)

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: Larry A Allen, MD, MHS served as guest editor for this article.

: Clinical trial registration: NCT00047437 and NCT01633398

¹: Co–primary authors.

²: The complete list of investigators is reported in the Supplementary material.

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Clinical InvestigationMultinational and multiethnic variations in health-related quality of life in patients with chronic heart failure

Background

Methods and results

Conclusions

Section snippets

Methods

Results

Discussion

Disclosures

Acknowledgements

JACC Heart Fail

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

Rev Esp Cardiol

JACC Heart Fail

JACC Heart Fail

Lancet

Heart Lung

Am Heart J

Lancet

Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial

JAMA

Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial

JAMA

Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims

Linking clinical variables with health-related quality of life. A conceptual model of patient outcomes

JAMA

Reliability and validity of the Kansas City cardiomyopathy questionnaire in patients with previous myocardial infarction

Eur J Heart Fail

Clinical Investigation
Multinational and multiethnic variations in health-related quality of life in patients with chronic heart failure