Sex Differences in Device-Measured Physical Activity After Transcatheter Aortic Valve Replacement

Abstract

OBJECTIVE: Physical activity (PA) is an important clinical and quality of life outcome after transcatheter aortic valve replacement (TAVR). We examined the effect of TAVR on objectively measured PA in patients with cardiac implanted electronic devices (CIEDs).

METHODS: Daily accelerometer data was obtained from CIEDs. Patients in the University of North Carolina Health System with continuous PA data at least 6 months before TAVR and 12 months after TAVR were included. Changes in activity pre- and post-TAVR were analyzed with linear mixed‐effects models using a random intercept for each patient. An interaction term was included to determine differences in PA between men and women pre- and post-TAVR.

RESULTS: Of the 306 patients with CIEDs who underwent TAVR, 24,655 patient-days of data from 46 patients, mean age of 82 years old, 44% of whom were female met inclusion criteria. A significant and sustained increase of 14.7% in daily PA was seen after TAVR [10.15 minutes per day, 95% confidence interval (CI) 8.75 to 11.56 P<.001] after adjusting for sex, obesity, race, history of depression, and Charlson Comorbidity Index. Effects were more prominent in women (18.57 [95% CI 16.36 to 20.79, P<.001] minute increase post-TAVR) compared to men (4.51 [95% CI 3.87 to 5.16] minute increase post-TAVR, P<.001).

CONCLUSIONS: This study demonstrates PA increases after TAVR with effects more pronounced in women than men. Further, this study highlights the potential use of remote monitoring data for monitoring functional outcomes in device patients after a procedure.

J INVASIVE CARDIOL 2023;35(7): E375-E384. doi: 10.25270/jic/23.00102

Key words: Transcatheter aortic valve replacement, defibrillator, pacemaker, activity

Introduction

Physical activity (PA) is an important clinical and quality of life outcome in patients with cardiac implanted electronic devices (CIEDs), as persistently low PA may have adverse effects on long-term mobility, morbidity, socialization, and independent living.¹ Elderly patients with CIEDs and severe aortic stenosis who undergo transcatheter aortic valve replacement (TAVR) may be at particular risk of poor functional outcomes after the procedure yet PA data on this cohort are lacking. Although previous studies have demonstrated short-term improvements in exercise capacity and functional independence following TAVR,^2,3 these studies were short in duration and relied on self-reported PA data which are susceptible to recall bias. Furthermore, few have studied the effect of sex on PA after TAVR, even though women account for a large proportion of patients treated with TAVR. Women with CIEDs also have different baseline characteristics and an increased risk of perioperative complications compared to men (ie, older age and fewer comorbidities),^4,5 which may influence mobility outcomes. Our study sought to determine the effects of TAVR on objective, CIED-measured, daily activity levels.

Methods

To address this gap in the literature, we leveraged longitudinal remote monitoring and clinical data from patients enrolled in the University of North Carolina Cardiovascular Device Surveillance Registry (UNC CDSR), a prospective, multicenter clinical research registry for all patients with CIEDs, including pacemakers, implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices, implanted at 9 UNC hospitals from 2010 to present. The UNC CDSR aggregates clinical data from electronic health records (EHR) and physiologic data from CIEDs, including daily PA data obtained from the accelerometer embedded in the CIED pulse generator. Patient acceleration that meets or exceeds a preprogrammed threshold (approximately 70 steps per minute) is considered an active minute and the total minutes of PA per day are stored in device memory. Physical activity time recorded by CIEDs is considered light‐intensity exertion that is equivalent to walking at a slow pace.⁶

We included all patients in the registry who were at least 18 years old with Medtronic or Boston Scientific ICDs or pacemakers implanted at least 30 days before the start of the study period to allow at least 30 days of post-implant recovery time which may influence physical activity. Patients were required to have at least 6 months of continuous activity data pre-TAVR and 12 months of activity data post-TAVR gathered by remote transmission or in-office device interrogations.

Covariates were selected a priori on the basis of their known association with PA and procedural recovery. Demographic variables (age, sex, race/ethnicity [black, Hispanic, white, or other], and marital status) and body mass index (BMI) were collected closest to the baseline date. BMI (calculated as weight in kilograms divided by height in meters squared) was dichotomized as obese (BMI ≥30.0 kg/m²) and nonobese (BMI <30 kg/m²), according to the World Health Organization/National Institutes of Health classification scheme.⁷ Comorbidities were considered present and assumed to persist if the International Classification of Diseases, Tenth Revision (ICD‐10) code for that specific condition was recorded in the EHR prior to the TAVR procedure. Patients with left ventricular assist devices were excluded, as were activity data collected during hospitalized days. The Charlson comorbidity index, comprising the sum of individual comorbidities, was calculated for each patient.⁸

Descriptive statistics were used to summarize the sample characteristics, and sex-specific comparisons were made with the Kruskal-Wallis test or by Pearson's Chi‐Squared tests, as appropriate. We used linear mixed‐effects models with daily PA values as the unit of analysis and a random intercept for each patient to compare PA trajectories pre- and post-TAVR. This analysis allows for correlations between repeated measurements on the same individuals. An interaction term for sex was added to examine sex differences in PA after TAVR. Effects are reported with 95% confidence intervals (CI). A two‐sided P-value of less than .05 was considered significant. All analyses were performed with R software, version 4.0.5 (R Core Team, 2021). This study was approved by Institutional Review Board at the University of North Carolina at Chapel-Hill.

Results

From the initial cohort of 306 patients with a CIED who underwent TAVR, 1 was excluded for undergoing left ventricular assist device implantation, and an additional 259 were excluded because they lacked continuous PA data throughout the study period. The analytic cohort included 24,655 patient-days of data from 46 patients, mean age of 82 years old, 44% of whom were female. Twenty-nine (63%) had pacemakers and 17 (37%) had ICDs with similar frequencies of medical comorbidities between men and women, as shown in Table 1.

The median activity of the cohort was 59.0 (interquartile range [IQR] 53.4-64.6) minutes per day over the 6 months pre-TAVR and 82.6 (IQR 72.4-92.9) minutes during the 12 months post-TAVR (43.7% increase). In the mixed-effects model, a significant and sustained increase in daily PA was seen after TAVR [10.15 minutes per day, 95% confidence interval (CI) 8.75 to 11.56, P<.001] after adjusting for sex, obesity, race, history of depression, and Charlson Comorbidity Index⁸ (Figure 1), corresponding to an 14.7% relative increase in daily PA. The cohort median daily activity in women pre-TAVR was 40.3 (IQR 34.3-46.3) minutes, increasing to 76.8 (IQR 59.5-94.0) minutes post-TAVR (90.5% increase). In men, activity increased from cohort median of 69.6 (IQR 61.5-77.7) minutes pre-TAVR to 86.7 (IQR 77.0-96.4) minutes post-TAVR (24.6% increase). This difference was further characterized using an interaction between TAVR status (pre/post) and sex, where women experienced an 18.57 (95% CI 16.36 to 20.79, P <.001) minute increase post-TAVR compared to 4.51 minutes in men (95% CI 3.87 to 5.16 minutes, P <.001), as shown in Table 2.

Discussion

Our study demonstrates that both men and women with CIEDs increase their daily PA after TAVR; however, women experienced a greater increase in daily activity post-TAVR even after adjusting for baseline differences. One possible explanation for this finding is that women with CIEDs may be more physically frail or deconditioned prior to TAVR, leading to more significant gains in activity after the procedure. Small observational studies using the 6-minute walk test have demonstrated increases in exercise capacity by as much as 20% 6 months after TAVR.³ Our results extend these findings in real-world scenarios leveraging objective PA data captured in the context of a patient’s routine operating environment rather than an observed testing mechanism, and over a longer follow-up period.

A previous analysis of the FRAILTY-AVR study demonstrated the deleterious effects of low activity pre-TAVR in older patients (median age 84 years) undergoing TAVR using questionnaire-based interviews quantifying habitual physical activity levels.⁹ Several other studies have focused on frailty as a prognostic factor for long-term outcomes post-TAVR, but these are often subjective or reliant on questionnaires^10,11 which are subject to recall bias, or, require complex indexing of billing codes.¹² Physical activity is a readily available metric on patients with CIEDs and may also be a valuable source of both baseline activity levels pre-TAVR as well as objective measurements of increased activity post-TAVR, as these activity levels have been shown to correlate with in-office frailty indicators.¹³ As proposed by Bartlett et al, using personal device-based data can also inform clinicians about an individual’s recovery process post-procedure.¹⁴

Strengths of this investigation include the examination of continuous daily PA data from patients in a large healthcare system over an 18-month follow-up period. However, findings should be interpreted in light of the small sample size, a predominantly white patient population, and observational design. In addition, although the UNC CDSR captures data from multiple hospitals located throughout North Carolina, this is a study of patients from a single healthcare system. Information on some clinical parameters known to affect PA and PA-related outcomes were not available for this study including NYHA (New York Heart Association) heart failure classification, device indication, ejection fraction, and data on lifestyle factors (eg, adherence to medical therapies, sleep and diet). Results from this study may not generalize to populations without implanted devices, although a recent study demonstrated similar outcomes in patients undergoing TAVR with pre-existing permanent pacemakers compared with patients that do not have pacemakers.¹⁵

Conclusions

Results from this investigation extend our understanding of changes in daily PA after TAVR, differences in activity by sex after TAVR, and lend support for ongoing randomized clinical trials to evaluate whether early initiation of exercise training programs (ie, cardiac rehabilitation programs) increase daily activity and improve clinical and quality of life outcomes after TAVR. Further, this study highlights the possible use of CIED data to monitor important functional outcomes in device patients after TAVR and other cardiovascular procedures.

Affiliations and Disclosures

From ^a Division of Cardiology, Department of Medicine, University of North Carolina Hospitals, Chapel Hill, North Carolina.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Gehi receives research funding from Bristol Myers Squib Foundation, consulting fees from iRhythm, Biotronik and speaker’s honoraria from Abbott, Zoll Medical. Dr. Cavender reports research support to his institution for studies in which he is the principal investigator (Amgen, Boehringer-Ingelheim, CSL Behring); consulting fees from Amgen, Bayer, Boehringer-Ingelheim, Medtronic, Merck, Novo-Nordisk. Dr. Rosman’s effort on this study was funded by a grant from the National Heart, Lung, and Blood Institute (K23HL141644). Dr. Rosman reports consultancy fees from Pfizer and Biotronik. The remaining authors have nothing to disclose.

Ethical Oversight: This study received oversight from the Institutional Review Board of the University of North Carolina.

Twitter Handles: @MazzellaMD, @anilgehi, @jvavalle, @LRosman_PhD

Manuscript accepted June 2, 2023.

Address for correspondence:  Lindsey Rosman, PhD, Assistant Professor of Medicine, CB 7075, 160 Dental Circle, 6025 Burnett-Womack Bldg., Chapel Hill, NC 27599-7075. Email: lindsey_rosman@med.unc.edu; Twitter: @LRosman_PhD

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