Effects of HIIT on HRV in Sub-acute Post-stroke Patients

A randomized controlled 2-arms parallel study, comparing HRV in two groups of stroke patients.

Post-acute stroke patients hospitalized in rehabilitation stroke¬-units, within secondary care hospitals, are screened for eligibility.

• Inclusion criteria:

• first-ever hemispheric stroke, with consistent clinical and neuroimaging signs
• <3 month
• NIHSS <20 in acute care
• age>18
• Non-inclusion criteria:

• complicated diabetes mellitus with objective neuropathy and/or autonomic dysfunction
• other concomitant cardiac or pulmonary diseases possibly affecting HRV recordings, ie: acute myocardial infarction (<6 month), myocardial dysfunction as severe dilated or hypertrophic cardiomyopathy, class 3 and 4 heart failure, arrhythmias including chronic atrial fibrillation, conduction abnormalities.
• beta-blockers with no alternative options
• severe cognitive impairment inconsistent with free, informed and written consent or questionnaire filling
• Patients will benefit beforehand from a symptom-limited Graded Exercise Test (GXT), with ECG monitoring and using a semi recumbent cycle ergometer (Ergoline, Optibike MED600), mainly to exclude a CV risk and to accurately assess their exercise capacities for better individualized programs. Peak oxygen uptake, Peak Power , Peak Heart Rate, Respiratory Exchange Ratio (VO2peak, Power peak, HRpeak, RER respectively) will be measured, Ventilatory Threshold 1 (VT1) will be estimated, and oxygen uptake, power and heart rate at VT1 will be recorded (VO2vt1, Pvt1, HRvt1).
• The standard-of-care neuro-rehabilitation program was carried out according to the international recommendations. It will consist daily in a mean of 3 sessions (2 to 4), five days a week: physiotherapy (with, among others, Strengthening-Stretching activity), occupational therapy, cognitive therapy (orthophonist or neuro-psychologist).

In addition, either aerobic training (HIIT) or non-aerobic training (Control Group-CG by Low Intensity Group Training-LIGT).

• HIIT and LIGT training volume and duration will be the same (16 sessions, 12 to 30' each, 6 weeks).

The intervention-group (HIIT Group) will realize a 6-weeks Aerobic Training as follows:

Among the FITT principle:

• Frequency: 2-3 times a week
• Intensity: long-HIIT: 4 to 5 four-minutes intervals at Pvt1(+/- 2 steps) interspersed with two-minutes interval at 50% Pvt1=(4-5 x (4':2')/(Pvt1 :50%Pvt1))

• short-HIIT: 8 to 10 forty-five seconds intervals at Pmax (+/- 2 steps) interspersed with forty-five seconds rest intervals = (8-10x(45":45")/Pmax :Rest))
• Time: 12' to 30' per session (8 short-sessions of 12 to 15', 8 long-sessions of 24 to 30')
• Type: cycling on a semirecumbent ergometer Depending on the patient's fatigue and progress, the intensity will be adjusted, with an HR target >80% HRpeak during intervals.

In the CG group, HIIT will be replaced by "LIGT" sessions, as follows:

Among the FITT principle:

• Frequency: 2-3 times a week
• Intensity: Low HR controlled by HR monitoring (<50% HRpeak or 30%HRR)
• Time: 12' to 30' per session (8 short-sessions of 12 to 15', 8 long-sessions of 24 to 30')
• Type: Static and Segmental strengthening and stretching mainly

• Measures taken to reduce bias:

-Patients' spontaneous physical activity will be monitored via two sets of four-day measurements, including weekends, using an Actigraph device worn on a belt.

• The primary endpoint will always be measured over 24 hours, at the same time of week; it will be read blind by the same cardiologist (single-blind).
• Known criteria for HRV modification will be monitored (side of the lesion, fever, blood pressure spike or hypoxia during measurement, medication intake).
• The other criteria will always be measured during the same half-day.
• In order to introduce a "blind component" for the patient (double-blind), the information provided to the patient will specify a "comparison between two different types of physical activity "
• At M6, only the primary endpoint will be measured. A Marshall questionnaire will be used at this time to verify the proportion of patients complying with WHO recommendations on physical activity at 6 months post-discharge.

Patients who would have been in the control-group will be proposed to enter in an out-patient (day-hospital) HIIT program.

• Novelty

• To use a new and strong risk marker of stroke relapse and post-stroke complications (mortality, morbidity, and poor functional outcomes), which is improved by physical activity, to strengthen the use of Aerobic Training (AT) in secondary prevention.
• To allow generalization of conclusions:

• by studying AT with a shorter intervention-design, limiting competition with neuro-rehabilitation (fatigue, time spent) and via a simple intervention-device (semi recumbent ergometer).

(Indeed, most of non-ambulatory participants (82% ) in RCTs benefited from AT through assistive walking devices, using Weight Bearing Support Treadmill, which are difficult to set up (accessibility, personnel and equipment costs…)).

• by studying AT effects in a more disabled population and at an early stage. (Indeed, in Randomized Controlled Studies having assessed AT in chronic (>6months) post-stroke patients, NIHSS ≤ 5/42 was most often chosen for inclusion criterion, with a median NIHSS around 3 at study start.

Inclusion criteria

• first-ever hemispheric stroke, with consistent clinical and neuroimaging signs
• <3 month
• NIHSS <20 in acute care

Exclusion criteria

• age<18 years-old
• diabetes mellitus complicated by neuropathy or autonomic dysfunction; or any other concomitant nervous system, cardiac or pulmonary disease possibly affecting the autonomic nervous system ie:
• myocardial infarction< 6 months,
• myocardial dysfunction as severe dilated or hypertrophic cardiomyopathy, class 3 and 4 heart failure,
• severe conduction abnormalities and arrhythmias, including chronic atrial fibrillation,
• mechanical ventilation,
• beta-blockers with no alternative options, pharmacological mandatory treatment possibly affecting the autonomic nervous system and HRV.
• severe cognitive impairment inconsistent with free, informed and written consent or questionnaire filling