Effects of strict versus lenient rate control on exercise capacity in atrial fibrillation: a retrospective analysis

Abstract

Background

Rate control is a primary treatment approach for managing atrial fibrillation (AF). However, a unified standard for the optimal level of control remains unestablished. This study aimed to investigate the impact of strict versus lenient heart rate control strategies on exercise capacity in patients with AF by assessing cardiopulmonary exercise test (CPET) results.

Methods

A total of 693 patients with AF were included in this study. The patients were categorized into three groups on the basis of their resting heart rate: strict rate control (resting heart rate < 80 beats per minute and heart rate during moderate exercise < 110 beats per minute), lenient rate control (resting heart rate < 110 beats per minute), and uncontrolled rate (resting heart rate ≥ 110 beats per minute. CPET indicators were compared across the different rate control strategies, and trend analyses were conducted to explore whether there was a correlation between heart rate control and exercise capacity.

Results

Significant differences in the maximum load, respiratory exchange ratio (RER), peak oxygen uptake (peak VO₂), peak oxygen pulse, and ventilatory equivalent (VE/VCO₂) at the anaerobic threshold were detected among the groups in the strict control, lenient control, and uncontrolled groups (all p < 0,05). However, no significant differences were detected in the anaerobic threshold or ventilation parameters among these groups. Trend analyses indicated that stricter heart rate control was associated with significant increases in maximum workload, peak VO₂, peak oxygen pulse, and ventilatory equivalent.

Conclusion

In patients with AF, strict heart rate control may enhance exercise capacity, suggesting the importance of effective heart rate management strategies.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12872-025-04961-9.

Key perspective

What is novel?

• This study provides novel insights into the comparative effects of heart rate control on exercise capacity in patients with AF. By employing cardiopulmonary exercise testing metrics, research revealed that strict rate control significantly enhances exercise capacity.

• These findings may inform and refine cardiac rehabilitation approaches, enabling more tailored and effective treatment strategies. Thid study introduces the novel concept of integrating strict heart rate control strategies into cardiac rehabilitation programs.

What are the clinical implications?

• Integrating strict heart rate control into cardiac rehabilitation programs can optimize patient outcomes by combining effective rate management with structured exercise training.

• By using cardiopulmonary exercise testing metrics to tailor heart rate control strategies, healthcare providers can develop individualized treatment plans that exercise capacity and overall health.

Background

Atrial fibrillation (AF) is one of the most prevalent cardiac arrhythmias worldwide and is a significant contributor to morbidity and mortality [1]. AF is significantly associated with major adverse outcomes, including mortality, ischemic stroke, and haemorrhage [2–4]. Despite the increasing incidence and prevalence of AF [5], the optimal management strategy is still debated in ongoing research. The two primary treatment strategies for AF patients are rate control and rhythm control. Rate control aims to manage symptoms and prevent complications by controlling the heart rate during episodes of AF, whereas rhythm control focuses on restoring and maintaining normal sinus rhythm [6–8]. Studies such as the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial have demonstrated no significant difference in survival outcomes between rate and rhythm control strategies, although rate control may offer certain advantages [9]. Consequently, rate control is implemented as the primary treatment choice [10], with an emphasis on stabilizing heart rates within a clinically acceptable range [11].

The Lenient versus Strict Rate Control II (RACE II) study evaluated the efficacy of strict versus lenient rate control strategies in patients with permanent AF and reported no significant differences in major clinical events, such as cardiovascular causes, stroke, and systemic embolism, between the two strategies. However, lenient rate control offered greater convenience for both patients and healthcare providers [12, 13]. The debate over the most effective rate control strategy continues. According to the 2024 ESC guidelines, lenient rate control is considered an acceptable initial approach unless symptoms such as severe heart failure or persistent symptomatic AF necessitate more aggressive control [14]. The 2023 ACC/AHA/ACCP/HRS guidelines recommend that for patients with nonheart failure AF, the target heart rate should be tailored to the patient’s underlying symptoms, typically aiming for a resting heart rate of < 100 to 110 beats per minute [15].

AF patients frequently experience a decline in exercise capacity, which significantly impacts their quality of life [16, 17]. This decline underscores the necessity for effective management strategies that address the functional limitations imposed by AF [18]. Understanding how different heart rate control strategies influence exercise capacity is crucial for improving treatment and patient health. Cardiopulmonary exercise testing (CPET) has become a valuable tool for assessing exercise intolerance and objectively evaluating functional capacity in clinical settings [19]. However, the effects of various heart rate control strategies on the exercise capacity of AF patients remain unclear. This study aims to explore the influence of different heart rate control strategies on exercise capacity in patients with AF by retrospectively analysing CPET indicators.

Methods

Study population

Between December 2012 and March 2023, a total of 11,454 patients who underwent CPET at Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences) were considered for inclusion in this retrospective study, primarily for the assessment of exercise capacity and functional evaluation in patients with cardiovascular diseases. The study was approved by the Ethics Committee of Guangdong Provincial People’s Hospital for retrospective data analysis (KY2023-514-03), and all procedures carried out during the study period were performed in accordance with relevant ethical guidelines.

The inclusion criteria for the study were as follows: (1) adults diagnosed with AF, and (2) patients who had completed standardized the CPET. The exclusion criteria included the following: (1) absence of resting heart rate data; (2) incomplete or prematurely terminated CPET; and (3) contraindications to CPET, including persistent unstable angina, severe aortic valve stenosis, acute decompensated heart failure, and others.

A total of 693 patients were included in the final analysis. These patients were stratified into three groups on basis of resting heart rate: strict control (resting heart rate < 80 beats per minute and heart rate during moderate exercise < 110 beats per minute), lenient control (resting heart rate < 110 beats per minute), and uncontrolled (resting heart rate ≥ 110 beats per minute). We retrieved clinical data, including medical history, medication history, demographic details, and CPET metrics, from the electronic medical records system. Before undergoing the CPET, all the participants provided written consent, which explicitly included both participation in the study and the CEPT procedure, and confirmed their understanding of the procedure.

Cardiopulmonary exercise test

CPET was performed via an electronically braked bicycle ergometer (ERG 910 plus, SCHILLER, Switzerland) in conjunction with breath-by-breath gas analysis facilitated by a calibrated metabolic cart (CARDIOVIT CS-200 Office Ergo-Spiro, SCHILLER, Switzerland). The resting heart rate was recorded after a sufficient rest period before the CPET to account for any transient effects of anxiety on heart rate. Patients were then categorized into strict control, lenient control, and uncontrolled groups according to their resting heart rate.

Peak oxygen uptake (peak VO₂) was defined as the highest level of oxygen consumption achieved at maximum exercise tolerance. The anaerobic threshold was determined through analysis of 10-second intervals of CO₂ output and O₂ uptake using the V-slope method. The peak oxygen pulse during exercise was calculated by dividing the peak heart rate by the oxygen uptake. Additionally, static pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), forced vital capacity ratio (FEV₁/FVC), and maximal expiratory flow (MEF), were conducted with patients in a seated position. These assessments provided comprehensive insights into respiratory function beyond the aerobic capacity evaluated during CPET.

Statistical analysis

We employed IBM SPSS Statistics 27.0 for the statistical analysis. Continuous variables were tested for normality using the Kolmogorov-Smirnov test. Normally distributed variables were presented as mean ± standard deviation, while non-normally distributed variables were reported as median (interquartile range). Categorical data were expressed as frequencies and percentages. To account for potential confounding factors in the intergroup comparisons, we employed analysis of covariance (ANCOVA) to evaluate exercise capacity, adjusting for key covariates such as age, sex, left ventricular ejection fraction (LVEF), coronary heart disease (CHD), valvular heart disease (VHD), and calcium channel blocker (CCB) use. Categorical variables were analysed using chi-squared tests. Multivariable linear regression models were further applied to examine the independent associations between heart rate control and exercise capacity, adjusting for the same covariates. We applied analysis of variance to calculate the P-trend values, evaluating the linear trend between heart rate control level and exercise capacity. All p values were calculated for two-sided tests, with significance set at p < 0.05.

Results

Patient characteristics

Table 1 provides the baseline demographic characteristics and comorbidities of the study population, stratified by heart rate categories. A total of 693 patients were included in this study, and categorized into three groups on basis of the level of heart rate control: the strict control group (n = 245), lenient control group (m = 336), and uncontrolled control group (n = 112). Compared with the lenient control and uncontrolled groups, the strict control group presented the highest mean age (61.07 ± 10.19 years vs. 56.52 ± 11.01 years vs. 55.81 ± 10.35 years, p < 0.001) and the greatest proportion of males (57.5% vs. 45.5% vs. 49.1%, p = 0.016).

Table 1.

Baseline characteristics of the study patients by heart rate control group

Variable	Strict Control	Lenient Control	Uncontrolled	P value
n	245	336	112
Age, y	61.07 ± 10.19	56.52 ± 11.01	55.81 ± 10.35	< 0.001
Male, n (%)	142(57.5)	153(45.5)	55(49.1)	0.016
Weight, kg	63.09 ± 12.12	60.89 ± 11.36	61.87 ± 10.44	0.076
BMI, kg/m2	23.60 ± 3.60	23.20 ± 3.22	23.49 ± 3.28	0.355
Rest HR, bpm	68.72 ± 7.34	93.13 ± 8.62	126.71 ± 3.28	< 0.001
Rest SBP, mmHg	125.06 ± 19.40	124.01 ± 19.61	124.05 ± 22.67	0.836
Rest DBP, mmHg	75.38 ± 10.88	77.64 ± 12.76	77.54 ± 15.47	0.124
LVEF, %	63(60, 67)	62(56, 65)	60(54, 65)	< 0.001
Comorbidities
CHD, n (%)	49(20.0)	31(9.2)	10(8.9)	< 0.001
HF, n (%)	15(6.1)	22(6.5)	6(5.4)	0.901
VHD, n (%)	161(65.7)	275(81.8)	105(93.8)	< 0.001
Hypertension, n (%)	69(27.9)	65(19.3)	19(17.0)	0.017
Diabetes, n (%)	30(12.1)	32(9.5)	5(4.5)	0.073
Hyperlipidaemia, n (%)	9(3.6)	12(3.6)	1(0.9)	0.324
PAH, n (%)	38(15.4)	61(18.2)	16(14.3)	0.526
Medications
β-blockers, n (%)	113(46.9)	175(52.4)	53(47.4)	0.386
RASI, n (%)	60(24.8)	63(18.9)	23(20.7)	0.226
CCB, n (%)	36(14.9)	28(8.4)	6(5.4)	0.007
Amiodarone, n (%)	51(21.2)	74(22.2)	34(30.6)	0.122
Digoxin, n (%)	86(35.5)	130(38.9)	53(47.7)	0.092
Rate-controlling medication count	1(0,2)	1(1,2)	1(1,2)	0.979

Continuous variables shown as mean ± SD or the median (IQR); categorical variables shown as count (percentage). RASI, renin-angiotensin system inhibitors

BMI body mass index, SBP systolic blood pressure, DBP diastolic blood pressure, HR heart rate, bpm beats per minute, LVEF ventricular ejection fraction, CHD coronary heart disease, HF heart failure, VHD valvular heart disease, PAH pulmonary arterial hypertension, CCB rate-controlling calcium channel blocker (verapamil or diltiazem)

No significant differences in BMI, resting blood pressure, incidence of heart failure or pulmonary arterial hypertension were observed. However, the strict control group demonstrated a higher incidence of CHD (20% vs. 9.2% vs. 8.9%, p < 0.001) and the use of CCB (14.9% vs. 8.4% vs. 5.4, p = 0.007) than did the lenient control and uncontrolled groups. No significant differences were found in the use of β-blockers, RASIs, amiodarone, or digoxin.

CPET outcomes by heart rate control

There were significant differences in CPET parameters across the strict control, lenient control, and uncontrolled groups (Table 2). Compared with the lenient control and uncontrolled groups, the strict control group had a higher maximum exercise workload, with a significant difference observed among the groups (80.85 ± 30.76 vs. 74.46 ± 31.07 vs. 71.10 ± 32.04, p = 0.005). In addition, the mean respiratory exchange ratio exceeded 1.1 across all groups, suggesting that the majority of patients achieved maximal effort during the CPET. We also found that the peak VO₂ was 18.13 ± 4.22 ml/kg per minute in the strict control group, 17.76 ± 4.56 ml/kg per minute in the lenient control group, and 16.99 ± 4.35 ml/kg per minute in the uncontrolled group, with a significant difference observed between the groups (p = 0.008). However, no significant differences in peak blood pressure or VO₂ at the anaerobic threshold were found among the three groups.

Table 2.

Cardiopulmonary exercise test parameters across rate control strategies in atrial fibrillation

	Strict Control	Lenient Control	Uncontrolled	P value
Exercise load time, seconds	453.17 ± 108.73	437.64 ± 121.17	427.60 ± 116.02	0.270
Maximum load, Watt	80.85 ± 30.76	74.46 ± 31.07	71.10 ± 32.04	0.005
RER	1.17 ± 0.15	1.17 ± 0.14	1.14 ± 0.14	0.021
Peak VO2, ml/min/kg	18.13 ± 4.44	17.76 ± 4.56	16.99 ± 4.35	0.008
Peak VO2, %pred	70.58 ± 18.87	66.17 ± 17.33	62.80 ± 17.33	0.035
ATVO2, ml/min/kg	12.69 ± 3.16	12.62 ± 3.82	12.93 ± 3.61	0.386
ATVO2%pred	49.56 ± 13.98	47.23 ± 13.36	48.12 ± 15.25	0.275
Peak HR, bpm	135.26 ± 30.95	161.90 ± 30.80	182.39 ± 21.64	< 0.001
Peak SBP, mmHg	163.92 ± 30.15	161.90 ± 30.80	158.63 ± 26.45	0.834
Peak DBP, mmHg	82.67 ± 14.61	85.23 ± 15.18	85.97 ± 17.06	0.170
Peak O2 pulse, mL/bpm	8.50 ± 2.95	6.63 ± 2.34	5.91 ± 1.99	< 0.001
FVC, L	2.89 ± 0.84	2.91 ± 0.85	3.35 ± 0.96	0.793
FEV1, L	69.61 ± 25.64	70.06 ± 31.08	66.35 ± 32.62	0.934
FEV1/FEC, %	3.20 ± 1.25	3.19 ± 1.17	3.82 ± 1.34	0.858
MEF50, L/sec	1.16 ± 0.52	1.08 ± 0.56	1.54 ± 0.64	0.178
MEF25, L/sec	2.51 ± 1.11	2.47 ± 1.02	3.25 ± 1.15	0.507
VE/VCO2 @AT	32.45 ± 4.81	33.72 ± 5.88	34.77 ± 5.88	0.002
VE/VCO2 slope	31.37 ± 6.86	32.99 ± 8.04	33.77 ± 8.15	0.059
PETCO2, mmHg	33.05 ± 4.36	32.43 ± 5.10	31.75 ± 5.36	0.383

Continuous variables shown as mean ± SD or the median (IQR); categorical variables shown as count (percentage)

RER respiratory exchange ratio, VO₂ oxygen consumption, AT anaerobic threshold, HR heart rate, SBP systolic blood pressure, DBP diastolic blood pressure, FVC forced vital capacity, FEV1 forced expiratory volume in 1 s, MEF maximal expiratory flow, VE/VCO₂ slope of the relationship between minute ventilation and carbon dioxide output, PETCO₂ end-tidal carbon dioxide pressure

Pulmonary function parameters were not significantly different among the three groups, indicating that heart rate control strategies did not substantially impact pulmonary function in patients with AF (Table 2). Moreover, VE/VCO₂ @AT was lower in patients who achieved strict rate control than in those in the lenient control and uncontrolled groups (32.45 ± 4.81 vs. 33.72 ± 5.88 vs. 34.77 ± 5.88, p = 0.002). Overall, strict rate control seemed to have a more pronounced effect on the CPET parameters than did lenient rate control. In multivariable linear regression models, strict control strategy is dependently associated with greater maximum load, peak VO₂, peak O₂ pulse and lower VE/VCO₂@AT after adjusting age, sex, LVEF, CHD, VHD and CCB use (Supplement Table 1: A-D).

Trends in exercise capacity

The trends of critical indicators in the CPET for different rate control groups stratified by the resting heart rate are shown in Fig. 1. As heart rate control became stricter, peak VO₂ significantly increased among patients with AF (p-trend = 0.015). Furthermore, both the maximum exercise workload and exercise load time also increased with stricter heart rate control (maximum exercise workload: 80.85 ± 30.76 vs. 74.46 ± 31.07 vs. 71.10 ± 32.04; p-trend = 0.015; exercise load time: 453.17 ± 108.73 vs. 437.64 ± 121.17 vs. 427.60 ± 116.02; p-trend = 0.005) (Table 2; Fig. 1). The peak O₂ pulse was significantly higher in the strict control group than in the lenient control group and uncontrolled group (8.50 ± 2.95 vs. 6.63 ± 2.34 vs. 5.91 ± 1.99, p-trend < 0.001). The other parameters did not significantly differ among the three groups (Fig. 2).

Fig. 1.

Flow Chart of Patients Undergoing Cardiopulmonary Exercise Testing at Guangdong Provincial People’s Hospital between December 2012 and March 2023

Fig. 2.

Associations between Rate Control of the AF Group and Exercise Capacity. Trends in CPET indicators with varying heart rate control levels: (A) exercise load time, (B)maximum load, (C)peak VO₂, (D)ATVO_2, (E) peak O₂ pulse, and (F) VE/VCO₂ slope. VO₂, oxygen consumption; AT, anaerobic threshold; VE/VCO₂, slope of the relationship between minute ventilation and carbon dioxide output

Discussion

This retrospective study provides valuable insights into the influence of heart rate control strategies on exercise capacity in patients with AF. We investigated the effects of different heart rate control levels on exercise capacity, as measured by peak VO₂. The peak VO₂ reflects the maximum rate of oxygen consumption during physical exertion and is a reliable indicator of cardiopulmonary function and exercise tolerance [20, 21]. Our findings indicate that patients in the strict heart rate control group achieved a higher peak VO₂ than did those in the lenient control group. Additionally, patients in the strict control group exhibited longer exercise load times and higher workloads during the CPET.

Interestingly, our findings contrast with those of previous studies suggesting that strict rate control does not impact exercise capacity in patients with AF [22, 23]. Our findings indicate that strict rate control is superior to lenient rate control in terms of exercise capacity. This discrepancy may stem from variations in sample size and patient demographics across studies. Our research included a larger, more diverse cohort without restricting the analysis to specific AF types. Recent findings also emphasize the possible benefits of strict heart rate control. For example, a study reported that maintaining the heart rate below 80 beats per minute at discharge may lead to better clinical outcomes for patients with HF and persistent AF [24]. Notably, while the peak VO₂ was significantly higher in the strict control group, the VO₂ at the anaerobic threshold did not significantly differ. These findings suggest that strict heart rate may enhance overall exercise capacity, but its effect on exercise intensity at the anaerobic threshold requires further investigation.

Several mechanisms may explain why strict heart rate control enhances exercise capacity in patients with AF. First, strict control of the ventricular rate ensures adequate ventricular filling and prevents tachycardia, thereby enhancing cardiac efficiency during physical exertion [25]. Second, strict heart rate control reduces myocardial oxygen consumption and improves coronary perfusion by prolonging the diastolic phase [26]. This better oxygen and nutrient delivery to the myocardium helps alleviate exercise-induced fatigue and enhances overall exercise capacity [27].

In addition to enhancing exercise capacity, strict heart rate control strategies may be closely associated with better quality of life, slowed age-related endothelial dysfunction, and lower mortality rates [22, 28]. The enhancement of cardiopulmonary function in patients with AF is a positive sign, indicating significant improvements in disease management and overall health status [10]. Improved exercise capacity, optimized hemodynamic, symptom relief, and better quality of life contribute to a lower risk of complications such as heart failure and stroke [22, 29]. These findings underscore the potential benefits of implementing strict heart rate control as part of comprehensive treatment strategies for AF. Furthermore, incorporating heart rate control strategies into cardiac rehabilitation programs could further optimize patient outcomes by combining structured exercise training with optimal heart rate management.

It was noteworthy that we also observed a trend indicating a potential correlation between stricter heart rate control and better exercise capacity. Previous studies have demonstrated that among patients with AF, those with a heart rate ≥ 100 beats per minute have a dose-response relationship with an increased risk of developing heart failure and mortality, whereas no such correlation was noted in those with a heart rate < 100 beats per minute [30]. In the future, randomized controlled trials could further confirm the impact of strict heart rate control on enhancing exercise capacity in patients with AF and compare the long-term results of strict and lenient heart rate control strategies.

Although the optimal heart rate control strategy for AF remains uncertain [15, 31], our study provides important insights into its impact on exercise capacity. These findings are essential for informing clinical practice and the development of future AF management guidelines. Future guidelines could consider strict heart rate control as a viable strategy to enhance exercise capacity and overall health status in patients with AF. This approach not only optimizes haemodynamic and alleviates symptoms but also potentially reduces the risk of complications such as heart failure and stroke. Integrating strict heart rate control strategies into cardiac rehabilitation programs could offer a holistic approach to managing AF, ensuring that patients receive comprehensive care that addresses both their cardiac and overall health needs.

Study limitations

This study has several undeniable limitations. First, our results are limited by the population studied, which consisted exclusively of patients with AF from a single centre and may not be representative of the entire Chinese population. Second, as a retrospective analysis, medication regimens were not protocolized. Although patients were instructed to withhold medications on the day of CEPT to minimize pharmacological effects, we could not account for potential long-term medication adjustments. Third, this study may have overlooked several potential confounding factors, such as exercise habits and musculoskeletal conditions that could exercise capacity, which require further investigation. However, we employed ANCOVA to minimize bias caused by known confounding factors as much as possible. Finally, the database does not distinguish between types of AF, so further research is necessary to differentiate the benefits of strict rate control strategies for different types of AF.

Conclusions

In patients with atrial fibrillation, strict rate control is associated with higher exercise capacity compared with lenient rate control. Additionally, exercise capacity trends to increase as heart rate control becomes stricter.

Abbreviations

AF

Atrial fibrillation

CHD

Coronary heart disease

CPET

Cardiopulmonary exercise testing

LVEF

Left ventricular ejection fraction

peak VO2

Peak oxygen uptake

VHD

Valvular heart disease

Authors’ contributions

Study conception and design was performed by JNC, HM. Data collection was performed by YTL, DJL, HFZ, and YXL. Analysis was performed by YTL, JSZand BQB.Writing was performed by JNC, QD, XYL, and HM. This manuscript was read and approved by all credited authors.

Funding

This project was supported by the grants from China Heart House- Chinese Cardiovascular Association TCM fund (CCA-TCM-032; 202342); the Guangzhou Municipal Science and Technology Program key projects (2023B03J1249); and Joint Funds from Guangzhou Science and Technology Project (2023A03J0531, 2024A03J0658).

Data availability

The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Ethics approval was granted by the Medical Research Ethics Committee of Guangdong Provincial People’s Hospital (KY2023-514), and all procedures carried out during the study period were performed in accordance with the Declaration of Helsinki. All patients provided written informed consent before the CPET. Given that this was a retrospective observational study, we did not register it on ClinicalTrial.gov.

Consent for publication

Not Applicable.

Competing interests

The authors declare no competing interests.