Coronary artery disease (CAD) is associated with autonomic dysfunction and is characterized by reduced heart rate variability (HRV) and impaired heart rate recovery. Regular exercise improves cardiovascular outcomes in CAD, with high-intensity interval training (HIIT) showing superior benefits compared to moderate-intensity continuous training (MICT). However, the full potential of exercise is not used in the clinical context since some of the training principles are neglected, contributing to a high number of exercise non-responders. HRV-guided training has been identified as an alternative prescription technique for cardiovascular endurance exercise and has contributed to greater improvements compared to standard prescriptions. Thus, this study aims to assess the chronic effects of exercise on cardiovagal modulation, baroreflex sensitivity, arterial stiffness, and cardiorespiratory fitness in patients with CAD, specifically determining whether heart rate variability-guided training yields different outcomes compared to a traditional prescription in a 12-week exercise intervention.
A total of 48 participants, will be recruited and randomized into one of 3 groups: high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and HRV-guided training. The intervention will consist of 12 weeks of supervised exercise, with 3 weekly sessions. Participants in the HRV-guided training group will have their exercise intensity adjusted based on their individual HRV profiles. Moderate- or high-intensity sessions are prescribed when the 7-day rolling average of LnRMSSD remains within the smallest worthwhile change (SWC). If it falls outside the SWC, low-intensity sessions or rest are recommended. In the HIIT group, sessions will consist of 4 bouts of 2 minutes at 80-90% HRR during the first 4 weeks, increasing to 6 bouts of 2 minutes at the same intensity in weeks 5-8, and progressing to 6 bouts of 2 minutes at 90% HRR in the final 4 weeks. In the MICT group, participants will perform continuous sessions starting with 2x10 minutes at 50-60% HRR in the first 4 weeks, progressing to 2x12 minutes at the same intensity in weeks 5-8, and increasing to 2x15 minutes at 60-70% HRR in the final phase. Cardiovagal modulation, cardiorespiratory fitness, BRS, and AS will be assessed at the baseline and after the 12 weeks of intervention.
Most cardiac rehabilitation programs use the "one-size-fits-all" approach, which is a limitation of the literature, leading to a large number of exercise nonresponders to changes in cardiorespiratory fitness. HRV-guided training seems to be a more individualized method of aerobic prescription and may lead to greater improvements in cardiorespiratory fitness and in cardiovagal modulation. This study will contribute to generate evidence regarding aerobic exercise prescription in cardiac rehabilitation.
aged over 18 years;
had angiographically documented CAD in at least one major epicardial vessel;
clinical evidence of CAD in the form of previous myocardial infarction;
clinical evidence of CAD in the form of coronary revascularization (coronary artery bypass grafting or percutaneous coronary intervention);
heart failure;
cardiac implantable defibrillators;
resynchronizing devices;
inability to comply with guidelines for participation in exercise testing and training.
Parallel
HIIT Intervention
Other interventionOver the first 4 weeks, participants will perform 4 bouts of 2 min of high-intensity exercise at 80-90% heart rate reserve (HRR), during the next 4 weeks, participants will perform 6 bouts of 2 min of high-intensity exercise at 80-90%HRR, while in the last 4 weeks participants will perform 6 bouts of 2 min of high-intensity exercise at 90%HRR). Exercise bouts will be interspersed by 2 min of active recovery at 50-60% HRR.
MICT Intervention
Other interventionOver the first 4 weeks participants in MICT will perform continuous exercise at 50-60% HRR (2x10'), during the next 4 weeks participants will perform continuous exercise at 50-60% HRR (2x12'), while in the last 4 weeks participants will perform continuous exercise at 60-70% HRR (2x15').
HRV-Guided Intervention
Other interventionFollowing a 10-day initial characterization period, where the HRV is measured with plethysmography continually during the night, with "Whoop" (https://www.whoop.com) device, the individual HRV profile is defined, still, participants will use the Whoop during all intervention to allow the updating of HRV profile. Then, considering the daily individual autonomic regulation, following a decision-making schema modified from Kiviniemi et al., (2007) \[21\], exercise intensity will be defined for the training session, i.e., if LnRMSSD7day-roll-avg remained inside the smallest worthwhile change (SWC) (SWC = 0.5 × standard deviation), high intensity or moderate-intensity training sessions is prescribed, if LnRMSSD7day-roll-avg fell outside SWC, low intensity or rest is prescribed, leading to different workloads from the predefined training programs.
Cardiovagal modulation
The R-R intervals will be derived from beat-to-beat blood pressure pulse intervals using finger plethysmography (Finapres Nova, Amsterdam, Netherlands), during all measures. Finger plethysmography-derived peak-to-peak intervals are highly correlated with electrocardiogram R-R intervals, with similar variability. The upstroke is determined using the pressure signal with a resolution of 2 ms, and the interval between the two consecutive upstrokes is measured. In the frequency domain, the two primary components are low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF: 0.15-0.40 Hz) spectra. Heart rate variability measures provide information primarily on vagal modulation with the LF power spectrum reflecting both sympathetic and parasympathetic modulation and HF reflecting the parasympathetic modulation of the R-R intervals. The LF/HF ratio is used as an indicator of sympathovagal dominance.
Cardiorespiratory fitness
An incremental CPET will be performed on a treadmill (Pulsar 3p, HP Cosmos) with mixing-chamber gas exchange measurements (Quark RMR w/CPET, Italy), according to Bruce modified protocol. A 12-lead electrocardiogram will be continuously monitored, and blood pressure will be assessed by auscultation using an aneroid sphygmomanometer. A cardiologist and an exercise physiologist will supervise the CPET. Before each test, the gas analyzer will be calibrated using ambient air standard calibration gases of known concentrations (16,7% O2 and 5,7% CO2). The turbine flowmeter of Cosmed will be calibrated with a 3L syringe. Data will be analyzed in 20 s average, and peak VO2 will be defined as the highest value attained in the last minute of effort
Baroreflex sensitivity
Spontaneous sequence method will be used to estimate BRS through the baroreflex module of FisioSinal \[25\]. This method emits about adjacent oscillations (ramps) in R-R and ( \> 4 ms) and systolic blood pressure (SBP) (SBP; \> 1 mmHg). Beat-to-beat SBP will be recorded using finger plethysmography (Finapres Measurement Systems, Amsterdam, Netherlands). A BRS event was defined as the overlap of BP ramps with concordant changes in R-R intervals. Hence, BRS will be defined as the average of the BRS slopes.
Local arterial stiffness
Carotid arterial stiffness indices will be assessed using eTRACKING technology (Arietta V60, Hitachi Aloka Medical Ltd, Mitaka-shi, Tokyo, Japan), using a 7.5 MHz linear array probe incorporating a 5 MHz Doppler transducer. In longitudinal view, the probe will be manipulated so that the intima of the artery is imaged clearly from both the anterior and posterior walls and a single scan line is aligned perpendicularly to the vessel walls at a site 20 mm proximal to the carotid bulb. On-screen cursors will be placed on the anterior and posterior intima-media borders to enable tracking of both walls. The corresponding displacement waveforms and diameter curve will be calculated using high-resolution online wall tracking ("E-track" technology), with a sampling rate of 1 kHz. Arterial pressure waveforms were obtained automatically in real-time by calibrating peak and bottom values with SBP and DBP measured with sphygmomanometry, as previously validated.
Regional Arterial Stiffness
Carotid femoral PWV, carotid-radial PWV, and femoral dorsalis PWV will be measured using a non-invasive automatic device (Complior, Alam Medical, France) with participants lied supine on a cushioned table. The common carotid artery, femoral, radial and dorsalis artery pressure waveforms will be recorded using 4 piezoelectric pressure mechanotransducers placed on each artery. The travel time distance will be defined as the tape measured distance over the body surface between the 2 recording sites of interest with distance being corrected by 0.8 factor for carotid femoral. All measurements will be performed by the same operator on the right side of the body after 10 pulse waveforms of enough quality (\> 90%).
Body composition
Dual-energy X-ray absorptiometry (DXA) (Hologic Explorer-W, fan-beam densitometer, software QDR for Windows version 12.4, Waltham, USA) will be used to estimate total and regional fat mass, lean body mass, bone mineral content, and density. A whole-body scan will be performed, and the attenuation of X-rays pulsed between 70 and 140 kV synchronously with the line frequency for each pixel of the scanned image that will be measured. Abdominal and gynoid body fat mass will be measured through partial analyses of the DXA scan, based on regions of interest set by default in the DXA settings.
Free living physical activity
ActiGraph GT9X accelerometers will be used to track daily physical activity (ActiGraph, Pensacola, FL). Participants will be required to wear the accelerometer on their non-dominant wrist to control their level of physical activity. During the intervention phase, participants will be asked to maintain their usual patterns of physical activity. Actilife®software (v.6.9.1; Fort Walton Beach, FL) will be used for device activation and download, while an open-source R package called GGIR version 2.6 will be used for processing. The accelerometer data will yield measures of time spent in sedentary behavior, volume, and intensity of physical activity (total minutes at light, moderate, and vigorous intensity, total counts, and counts/minute), and how each of these behaviors is compounded (i.e., periods spent engaging in physical activity or sedentary behavior).
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Faculdade de Motricidade Humana
Lead sponsor
Fundação para a Ciência e a Tecnologia (FCT)
Collaborator
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