Feeling Better vs. Doing More: Why KCCQ and MVPA Belong Together in Heart Failure Trials

Clinical trials have long struggled to capture what heart failure truly takes from a patient. Survival and hospitalization rates tell one part of the story, but they say little about whether someone feels well enough to live their life. Two complementary tools, patient-reported questionnaires and wearable activity monitors, are helping researchers close that gap, and understanding how they work together is increasingly central to modern trial design. 

All-cause mortality was the definitive endpoint in landmark heart failure trials, but as survival improved, hospitalizations and patient-reported outcomes entered the picture. The Kansas City Cardiomyopathy Questionnaire (KCCQ) became the standard patient-reported outcome measure (PROM), while wearable accelerometers now provide continuous, objective measures of real-world activity, with moderate-to-vigorous physical activity (MVPA) emerging as a leading digital measure. ^[1,2] 

While these endpoints are often perceived to capture similar concepts (physical functioning), but KCCQ and wearable-derived measure genuinely different constructs and using them side by side yields a fuller picture of a therapy's effect than either alone.^[3] 

What KCCQ captures: how patients perceive their health 

The KCCQ is a 23-item, self-administered questionnaire assessing HF impact over the prior two weeks across seven domains (physical limitation, symptom stability/frequency, and burden, self-efficacy, quality of life, social limitation). Scores roll up into summary measures on a 0–100 scale (higher = better health status). The FDA has qualified the KCCQ-23 (Total Symptom Score, Physical Limitations Score, and Clinical Summary Score) as a Clinical Outcome Assessment (COA); a JACC state-of-the-art review confirms it validly and sensitively captures HF's impact and is strongly associated with clinical events.^[4,5] 

That association is robust at the trial level. A2026 meta-regression of 12 phase-3 HF trials (both HFrEF and HFpEF) found treatment-induced KCCQ changes significantly correlated with effects on cardiovascular death + HF hospitalization and with each component individually. The authors frame KCCQ as a promising candidate intermediate endpoint, but the signal is consistent enough that contemporary trials use it prominently. For example, the SUMMIT trial of tirzepatide in HFpEF with obesity used change in KCCQ Clinical Summary Score as one of two co-primary efficacy endpoints alongside a clinical event composite.^[6,7] 

Crucially, KCCQ is a patient-reported outcome measure (PROM): it reflects how patients feel and how limited they believe they are. That is its strength and its boundary. 

What MVPA captures: what patients actually ‘do’ 

MVPA, derived from wrist/hip accelerometers, such as ActiGraph LEAP, sits on the other side of that boundary. Regulators describe sensor-based digital health technologies as producing "objective" measures of behavior/physiology, distinct from PROMs that capture perceptions. An accelerometer does not ask how active someone feels; it records how much they moved and at what intensity according to a prespecified analytic algorithm.^[8] 

In HF, the picture is sobering. An accelerometer study found HF patients spent a median of ~12 min/day in MVPA versus ~56 min/day in healthy controls (severely curtailed activity). Importantly, average acceleration correlated moderately with the six-minute walk test (6MWT) and peak VO2, but not with quality of life. Objective daily movement and conventional clinical markers largely track different things.^[9] 

Why they complement rather than duplicate 

The case for using both rests on a simple, recurring finding: KCCQ and accelerometer-measured activity are related, but only modestly. They point in the same general direction without collapsing into the same signal, precisely what we want from complementary endpoints. 

ActiGraph LEAP + KCCQ: the practical pairing 

ActiGraph LEAP is a wearable-based digital health solution that captures MVPA and other activity metrics in real-world settings. Pairing LEAP with KCCQ informs us: 

• Whether the patient believes their life has improved (perceived health status and symptom burden on KCCQ)

• Whether their behavior in the world actually changed (objective minutes of MVPA per day) 

For trial teams, the scientific value lies not only in showing that both move, but also in understanding what it means when they do not. KCCQ improvement with stable MVPA may suggest symptomatic benefit without behavioral translation, while MVPA improvement without clear KCCQ change may suggest increased function that patients do not yet perceive as meaningful.  

The DETERMINE trials found that patients with lower wearable-measured activity tended to have lower 6MWT distances and lower KCCQ scores, but correlations among these measures were weak to modest. Investigators concluded accelerometer-based activity offers additional, complementary information beyond established outcomes. Dual assessment therefore strengthens interpretation in both concordant and discordant scenarios and provides a fuller picture to the researcher. ^[3] 

Practical and regulatory considerations 

Regulatory-wise, KCCQ enters with strong pedigree as an FDA-qualified COA, whereas accelerometry-based activity measures are still maturing as qualified endpoints with no drug approval yet based on an sDHT-derived primary endpoint in the US. The FDA has built infrastructure: a Digital Health Technologies (DHT) Framework under PDUFA VII, December 2023 guidance on DHTs for remote data acquisition, and qualification pathways including ISTAND and the DDT-COA program. Sponsors should seek health-authority advice early when MVPA will influence key efficacy conclusions or external claims. ^[11,12,13] 

The takeaway 

HF care has converged on helping patients feel better, function better, and live longer. KCCQ and MVPA each answer a different part: one captures lived perception of symptoms/limitation; the other captures objective daily behavior. The two measures correlate enough to reinforce each other and differ enough to each add information. For trialists designing the next generation of HF studies, the most defensible position may not be choosing between questionnaire and wearable but treating them as two lenses on the same patient and reading them together.  

About the Authors

Marcela Roy, MA, ACC serves as Executive Director of Clinical Science & Medicine, bringing over 20 years of clinical and research expertise to her role. She provides strategic leadership across CNS and non-CNS therapeutic areas, with particular expertise in psychedelic research and central ratings data quality monitoring methodologies.

Christine Guo leads Ametris’ clinical and data science team. She has over 15 years of clinical research experience and a passion for leveraging data and technology to improve people’s health. Prior to Ametris, Christine was Head of Scientific Innovation at Biogen Healthcare Solutions, leading the clinical development and validation of Biogen’s digital medicine products in multiple sclerosis, neuromuscular and neurodegenerative diseases.   

Dr. Elias Ketiar serves as the Clinical Vice President, Science & Medicine, at Signant Health. Dr. Ketiar draws on his wealth of more than 20 years of academic and clinical experience to advise on clinical trial design, execution, and governance. 

Lauren Crooks, MSc, has comprehensive cross-functional experience within the life sciences and information technology sectors. At Signant, she combines this experience to provide scientific consultation and support to clients on the implementation of eCOA to optimize patient care and outcomes in clinical trials. She has supported eCOA projects across multiple therapeutic areas, including dermatology and neurology, with a current focus on respiratory diseases. 

References:

[1] Reza N, Butler J. Assessing health status after discharge for decompensated heart failure: a patient-centred priority. Eur J Heart Fail. 2022;24(6):1030–1032. doi:10.1002/ejhf.2521 

[2] Critical Path Institute, ActiGraph, University of Canberra. C-Path, ActiGraph, and University of Canberra collaborate to generate evidence to support regulatory qualification of novel digital health technology measures in chronic heart failure. January 30, 2024. https://c-path.org/c-path-actigraph-and-university-of-canberra-collaborate-to-generate-evidence-to-support-regulatory-qualification-of-novel-digital-health-technology-measures-in-chronic-heart-failure/ 

[3] Docherty KF, Buendia Lopez R, Folkvaljon F, et al. Wearable Accelerometer-Derived  Measures of Physical Activity in Heart Failure: Insights From the DETERMINE Trials.  
J Card Fail. 2025;31(4):689-703. doi:10.1016/j.cardfail.2024.10.439 

[4] U.S. FDA. DDT COA #000084: KCCQ. April 9, 2020. https://www.fda.gov/media/136862/download 

[5] Spertus JA, Jones PG, Sandhu AT, Arnold SV. Interpreting the Kansas City  
Cardiomyopathy Questionnaire in clinical trials and clinical care: JACC state-of-the-art review. J Am Coll Cardiol. 2020;76(20):2379– 2390. 
doi:10.1016/j.jacc.2020.08.045  

[6] Fukuta H, Goto T. Association between treatment-induced changes in the Kansas City Cardiomyopathy Questionnaire and clinical outcomes in chronic heart failure: a trial-level meta-regression analysis. IJC Heart & Vasculature. 2026;63:101881. doi:10.1016/j.ijcha.2026.101881 

[7] Packer M, Zile MR, Kramer CM, et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2025;392(5):427-437. doi:10.1056/NEJMoa2410027. (Published online Nov 16, 2024.) 

[8] U.S. Food and Drug Administration. Digital Health Technologies for Remote Data Acquisition in Clinical Investigations: Guidance for Industry, Investigators, and Other