Examining the impact of blood flow restriction on cardiac rehabilitation outcomes

Table 1 Summary of studies using blood flow restriction in patients with cardiovascular disease

Ref.	Study groups	Study population	Exercise modality	Training protocol (Exercises, intensity, sets x reps or time, rests, velocity contractions)	Intervention duration	Exercise frequency	Position	Arterial occlusion pressure and type of occlusion	Cuff width and length
Fukuda et al[29] (2013)	BFR (n = 6). CON (n = 6). Same participants	Patients with cardiovascular disease (5 with old myocardial infarction and 1 dilated cardiomyopathy). 69 ± 12 years	BFR RT	BFR RT: Biceps flexion exercises using an elastic band. 4 sets. 30 reps + 3 × 15 reps, 30 second rest. 2.4 seconds per repetition (1.2 seconds concentric, 1.2 seconds eccentric) CON: Same RT exercises without BFR	Not applicable (acute effects)	Not applicable (acute effects)	Proximal region of both arms	110–160 mmHg. Continuous	30 mm width
Groennebaek et al[30] (2019)	BFR (n = 12). RIC (n = 12). CON (n = 12)	Patients with congestive heart failure. 63.66 ± 8 years	BFR-RT	BFRRT: 4 sets of bilateral knee-extensions to the point of volitional fatigue at a load corresponding to 30% of maximal dynamic strength. 30 seconds inter-set recovery in which the cuffs remained inflated. RIC: 4 cycles of 5 minutes upper arm ischemia followed by 5 minutes of reperfusion. Control: No treatment	6 weeks	3 times/week	Lower body	50% (AOP). Continuous	14 cm
Ishizaka et al[31] (2019)	BFR 10% RT (n = 7) BFR 20% RT (n = 7). 10% non-BFRRT (n = 7). 20% non-BFRRT (n = 7). Same participants	Patients with cardiac disease (not specify which one), mean age: 48 years	BFR-RT	Bilateral knee extension at 10%-20% 1RM. 3 sets of 30 trials with 30 second of rest between sets and 5 min of rest between conditions	Not applicable (acute effects)	Not applicable (acute effects)	Proximal region of both legs (implied)	180 mmHg. Continuous	60 mm width
Kambič et al[26] (2019)	BFR (n = 12). CON (n = 12)	Coronary artery disease patients. 60 ± 2 years	BFR-RT	BFRRT: Unilateral leg extension: 3 sets (8, 10, 12 reps). Intensity: 30%-40% 1-RM, increased biweekly. 45 seconds inter-set rest interval. Cadence: 1 second concentric, 2 seconds eccentric. CON: Standard care	8 weeks	2 ×/week (BFR)	Medium part of each thigh	15-20 mmHg > resting SBP. Continuous	23 cm width, 42-50 cm length
Kambič et al[32] (2021)	BFR (n = 12), CON (n = 12)	Coronary artery disease patients. 60 ± 2 years	BFR-RT + aerobic training	BFRRT: 3 × 8-12 reps at 30%-40% 1-RM. 45 seconds inter-set rest interval. Cadence: 1 second concentric, 2 seconds eccentric. CON (aerobic rehabilitation): Interval leg cycling at the 60% to 80% of maximal heart rate (5 intervals of 5 minutes of workload cycling followed by 2 minutes of loading cycling) and cadence 50 to 60 rpm	8 weeks	Not stated (baseline: 2 ×/week). 3 ×/week (control)	Proximal region of both thighs (implied)	15-20 mmHg > resting SBP. Continuous	23 cm width, 42–50 cm length
Madarame et al[33] (2013)	BFR (n = 9), CON (n = 9). Same participants	Patients with stable ischemic heart disease, 57 ± 6 years	BFR-RT	Low-intensity RT. 4 sets (1 set of 30 rep + 3 sets of 15 rep) of bilateral knee extension exercise with a load of 20% 1RM. 30-second rest between each set. Control: Same exercise without BFR	Not applicable (acute effects)	Not applicable (acute effects)	Not stated	200 mmHg. Continuous	50 mm width
Nakajima et al[34] (2010)	KAATSU (n = 7)	Patients with ischemic heart disease, 52 ± 4 years	KAATSU-RT	Low-intensity KAATSU RT, 4 sets (1 set of 30 rep + 3 sets of 15 rep) of leg press, leg curl and leg extension. 1 min rest between each set. 20%-30% of 1RM. 1.5 seconds for each phase (concentric-eccentric)	3 months	2 ×/week	Not stated	100-250 mmHg. Continuous	Not stated
Ogawa et al[27] (2021)	KAATSU (n = 11), CON (n = 10)	Early post-cardiac surgery patients. 69.6 ± 12.6 years	KAATSU-RT	KAATSU RT: Seated knee extension and flexion and leg press. 1.5 seconds for each phase (concentric-eccentric). 3 sets of 30 repetitions for each exercise with 30 second of inter-set rest. 20%-30% 1RM. Control (aerobic cardiac rehabilitation): 30 min aerobic exercise at anaerobic threshold on a cycle ergometer	3 months	2 ×/week	Base of each thigh	100-200 mmHg. Continuous	5 cm width
Tanaka and Takarada[35] (2018)	BFR (n = 15), CON (n = 15)	Patients with post-infarction heart failure 60.7 ± 11.1 years	BFR-AT	BFR-AT: 15 minutes of Cycle ergometer at 40%–70% peak VO2/W. CON: Same exercise without BFR	6 months	3 ×/week	Proximal ends of thighs	40-80 mmHg increase in the systolic blood pressure that is required for vascular occlusion (208.7 ± 7.4 mmHg). Continuous	Width: 90 mm; length: 700 mm

BFR: Blood flow restriction; CON: Control group; RT: Resistance training; BFRRT: Blood flow restriction resistance training; RIC: Remote ischemic conditioning; 1RM: One repetition maximum; AOP: Arterial occlusion pressure; SBP: Systolic blood pressure.

Table 2 Summary of the main findings of the included studies on blood flow restriction in patients with cardiovascular disease

Ref.	Study population	Main findings	Safety	Adherence
Fukuda et al[29], 2013	n = 6 (male). 69 ± 12 years. Patients with cardiovascular disease (5 with old myocardial infarction and 1 dilated cardiomyopathy)	Acute effects: ↑↑ muscle activation biceps brachii ↑↑ muscle hypertrophy biceps brachii	Information not reflected in the manuscript	Information not reflected in the manuscript
Groennebaek et al[30], 2019	n = 36 (male). 63.66 ± 8 years. Patients with congestive heart failure	Chronic effects: ↑↑ Functional capacity (6MWT), ↑↑ Maximum isometric strength, ↑↑ quality of life, ↑↑ mitochondrial function	No severe adverse events were recorded, but all patients experienced mild vertigo	100%
Ishizaka et al[31], 2019	n = 7 (6 male) mean age: 48 years. Patients with cardiac disease (not specify which one)	Acute effects: ↑↑ Electromyography muscle activity of rectus femoris, VL, and VM at 10% and 20% intensity	Information not reflected in the manuscript	Information not reflected in the manuscript
Kambič et al[26], 2019	n = 24 (18 male). 60 ± 2 years. Coronary artery disease patients	Chronic effects: ↑↑ muscle strength, ↓↓SBP, (NC) VL diameter, (NC) brachial artery flow-mediated vasodilation, (NC) insulin sensitivity	No training-related adverse events were recorded	100%
Kambič et al[32], 2021	n = 24 (18 male). 60 ± 2 years. Coronary artery disease patients	Chronic effects: ↓↓ SBP, ↓DBP, (NC) N-terminal prohormone B-type natriuretic hormone, (NC) Fibrinogen, (NC) D-dimer. Acute effects: ↑↑ Heart rate, ↓↓SBP and DBP in the third set	No training-related adverse events were recorded	100%
Madarame et al[33], 2013	n = 9 (7 men). 57 ± 6 years. Patients with stable ischemic heart disease	Acute effects: ↑↑ Plasma noradrenaline, ↑↑ plasma D-dimer, ↑↑ high sensitive C-reactive protein, (NC) fibrinogen/fibrin degradation products, (NC) heart rate	Relative safety	100%
Nakajima et al[34], 2010	n = 7 (7 men). 52 ± 4 years. Patients with ischemic heart disease	Chronic effects: ↑↑ leg press, leg curl and leg extension strength, ↑↑ muscle CSA of quadriceps femoris, hamstring and adductor, ↑↑ VO2peak, ↑↑ VO2AT, (NC) IGF-1, (NC) hsCRP	No training-related adverse events were recorded	100%
Ogawa et al[27], 2021	n = 21 (18 male). 69.6 ± 12.6 years. Early post-cardiac surgery patients	Chronic effects: ↑↑ anterior mid-thigh thickness, ↑↑ skeletal muscle mass index, ↑↑ knee extensor strength, ↑↑ walking speed, (NC) CPK, (NC) D-dimer, (NC) handgrip strength	No adverse events were recorded	Information not reflected in the manuscript
Tanaka and Takarada[35], 2018	n = 30 (30 male). 60.7 ± 11.1 years. Patients with post-infarction heart failure	Chronic effects: ↑↑ Peak VO2/W, ↑↑ Serum BNP levels, ↑↑ C-reactive protein, (NC) Weight, (NC) BMI, (NC) thigh circumference, (NC) anaerobic threshold, (NC) VE, (NC) VCO2, (NC) gradient of the VE–VCO2 relationship, (NC) Blood urea nitrogen, (NC) Creatinine, (NC) eGFR, (NC) Glucose, (NC) HbA1c, (NC) TG, NC HDL-C, (NC) LDL-C, (NC) Urid acid.	No serious adverse events were recorded	Information not reflected in the manuscript

↑/↓: Trends to positive changes but with no significant changes; ↑↑/↓↓: Indicate statistically significant changes (reported P < 0.05) changes, the arrow direction denotes the increase (↑) or decrease (↓) of the variable; NC: No change; 6MWT: Six-minute walk test; EM: Electromyography; GRF: Ground reaction force; VL: Vastus lateralis; VM: Vastus medialis; RF: Rectus femoris; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; CSA: Cross-sectional area; BMI: Body mass index; Peak VO₂/W: Peak oxygen consumption per unit of body weight; Serum BNP levels: Serum brain natriuretic peptide levels; AT: Anaerobic threshold; VE: Ventilation; VCO₂: Volume carbon dioxide; BUN: Blood urea nitrogen; eGFR: Estimated glomerular filtration rate; HbA1c: Glycated hemoglobin; TG: Triglycerides; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; SMI: Skeletal muscle mass index; CPK: Creatine phosphokinase; IGF-1: Insulin-like growth factor 1; hsCRP: High-sensitivity C-reactive protein.

Table 3 Main setting for programming blood flow restriction in cardiovascular disease

Programming variable		Details
Exercise protocol	Type of exercise	Resistance training was common, using exercises such as knee extension, leg press or biceps flexion. Aerobic exercise was also employed (i,e. cycle ergometer)
	Exercise intensity	Low intensity predominated: Resistance exercise at 10%-40% of 1RM; aerobic exercise at about 40%-70% of estimated maximal oxygen uptake (VO2max) or 60%-80% heart rate
	Sets and repetitions	Typical protocol: 1 × 30 reps followed by 3 × 15 reps. Other variations included 3 × 15 reps or 3 × 30 reps
	Rest interval	Rest periods ranged from 30 to 60 seconds between sets
	Targeted muscles/Limbs	Both lower limbs (e.g., thigh/knee extensions, leg press) and upper limbs (e.g., elbow flexion) were trained; many protocols used bilateral exercise
	Session frequency	Varied by protocol-examples include once per week in acute sessions and twice or three sessions per week in multisession studies
	Intervention duration	Ranged from single sessions or 1–3 acute sessions to multiweek protocols (e.g., 8-16 sessions over 8 weeks or 3 months). Chronic effects remain poorly characterized
BFR protocol	BFR pressure values	Highly variable: Examples include fixed pressures of 200 mmHg, ranges of 100–250 mmHg, 50% of AOP, or 15-20 to 40-80 mmhg > resting SBP
	Pressure determination	Methods included arbitrary fixed pressures, percentages of SBP or percentage of AOP. A lack of consistent use of % AOP was noted
	Cuff width	Varied widely-from 3 centimeters (cm) inelastic cuffs to 23 cm. Wider cuffs (> 12 cm) are recommended for safety and comfort, as they require lower inflation pressures to achieve occlusion
	Cuff type	Both pneumatic cuffs with manometers and inelastic cuffs were used.
	Occlusion protocol	Occlusion was applied continuously throughout sets and rest intervals. Cyclical occlusion–reperfusion has been discussed in heartfailure contexts but was not detailed in these acute/shortterm studies

BFR: Blood flow restriction; 1RM: One repetition maximum; VO₂max: Maximal oxygen uptake; SBP: Systolic blood pressure; AOP: Arterial occlusion pressure.