High-intensity interval training for health benefits and care of cardiac diseases - The key to an efficient exercise protocol

Table 1 Variables improved by high-intensity interval training

Variables	Target
Skeletal muscle biopsy
PGC-1α
Mitochondrial function in lateral vastus	O2 consumption
Fatty acid transporter in the vastus lateralis and FAS (a key lipogenic enzyme)
IR β subunit in skeletal muscle (peripheral insulin sensitivity)	Metabolic
Re-uptake of Ca2+ into the salcoplasmic reticulum
Physiological test
Exercise test
Improvement of ventilatory efficiency (increased value of PETCO2)	Respiratory function
Oxygen consumption at the first ventilator threshold	Cardiac function
Oxygen pulse	Cardiac function
Parasympathetic activity (HR recovery)	Autonomic function
Duration of exercise time	Autonomic function
Distance walked during the 6-min walk	Work capacity
Ultrasonography
Cardiac function
Reversed LV re-modelling (LV end diastolic and systolic volumes)	Cardiac function
Ea
Diastolic function (e′, E, E/ e′, E/A ratio, higher proportion of e′ > 8 cm/s, E improvement during exercise),
Systolic function after 12 wk at rest and during exercise)
E reduction
Deceleration time increase
Left atrial volume
Reduced-plasma BNP
Vascular
Endothelial dysfunction (FMD)	Vascular function
Coronary plaque necrotic core reduction in defined coronary segments	Vascular function
Laboratory test
Myeloperoxidase	Anti-oxidant
High sensitivity CRP	Inflammation
Interleukin-6
insulin sensitivity (HOMA index)	Metabolic
HbA1C
Clinico-social data
Increased Short Form-36 physical/mental component scores and decreased Minnesota Living with Heart Failure questionnaire score	Quality of life
Frequency of metabolic syndrome	Risk factor

HOMA: Homoestasis model assessment; IR: Insulin receptor; PGC: Peroxisome-proliferator activated receptor γcoactivator; FMD: Flow mediated dilation; FAS: Fatty acid synthase; PETCO₂: End-tidal carbon dioxide; HR: Heart rate; LV: Left ventricular; BNP: Brain natriuretic peptide.

Table 2 Mode, intensity, and VO_2peak increment in high-intensity interval training versus moderate-intensity continuous training in randomized controlled trials (coronary artery disease)

Study	Published yr	Sample	n	HIIT	MCT	Duration	Mode	VO2peak pre		VO2peak %increase
								HIIT	MCT	HIIT (%)	MCT (%)
1 Rognmo et al[28]	2004	CAD	17 (HIIT = 8)	3 d/wk 4 x 4 min@80%-90% VO2peak total 33min	3 d/wk 41 min@50%-60% VO2peak isoload to HIIT	10 wk	TM	31.8	32.1	17.9a	7.9
2 Warbur-ton et al[41]	2005	CAD (previous CABG or AP)	14 (HIIT = 7)	2 d/wk, 2 min@90%VO2R, 2 min recovery, 30 min total	2 d/wk 30 min @65%VO2R, average training volume similar to HIIT	16 wk	TM etc1	22	21	31.8a	9.5
3 Tjønna et al[21]	2008	Metabolic syndrome	28 (HIIT = 9)	3 d/wk 4 × 4 min@90%HRmax, 3 min active recovery @70% HRmax 40 min total	3 d/wk 47 min @70% HRmax, equalized training volume	16 wk	TM	33.6	36	35a	16
4 Moholdt et al[43]	2009	post CABG	59 (HIIT = 28)	5 d/wk 4 × 4 min@90%HRpeak, 3 min recovery	5 d/wk 46 min + Aerobic group exercise, iso energic to HIIT	4 wk	TM	27.1	26.2	12.1	8.8
5 Moholdt et al[40]	2011	post MI	89 (HIIT = 30)	2 d/wk 4 × 4 min@85%-95%HRpeak, 3 min recovery	2 d/wk 60 min@58% PPO	12 wk	TM1	31.6	32.2	14.6a	7.8
6 Rocco et al[23]	2012	CAD	37 (HIIT = 17)	3 d/wk 7 × 3 min@RCP, 7×3 min recovery@VAT total 42 min	3 d/wk 50 min@VAT	3 mo	TM	18	17.9	23.3	24.6
7 Currie et al[51]	2013	recent event CAD post PCI, CABG, etc	22 (HIIT = 11)	2 d/wk 10 × 1 min@89% (80%-104%) PPO, 1 min recovery@10%PPO, 1 d/wk home-based @similar intensity	2 d/wk 30-50 min @58% PPO, 1d/wk home-based @similar intensity not isocaloric	12 wk	bike	19.8	18.7	24	19
8 Keteyian et al[38]	2014	Stable CAD (post MI CABG and/or PCI)	28 (HIIT = 15)	3 d/wk 4 × 4 min@80%-90%HHR	3 d/wk 30 min@60%-70%HRR	10 wk	TM	22.4	21.8	16a	8
9 Madssen et al[39]	2014	CAD with stents	36 (HIIT = 16)	3 d/wk 4 × 4 min@85%-95%HRpeak, 3 min active recovery@70%HRpeak	3 d/wk 46 min@ 70%HRmax, isocaloric	12 wk	TM	31.2	29.8	10.6a	6.7
10 Conraads et al[19]	2015	CAD	173 (HIIT = 85)	3 d/wk 4 × 4 min@90%-95%HRpeak, 3 min active recovery	3 d/wk 37 min@ 70%-75% %HRmax	12 wk	bike	23.5	22.2	22.7	20.3

Adapted from Ito S et al. Internal Medicine. 2016; 55: 2329-2336.

^a in VO_2peak % increase raw: There is significant difference in % increase of VO_2peak between HIIT and MCT. 4 × 4 min means 4 × 4 min intervals per one HIIT training session. Study 2: ^a data shown is VO₂ at anaerobic threshold. Data is shown in figure without exact value at VO_2peak (30+ in HIIT 30 in MCT)., and %increase at peak exercise is similar. TM etc¹ means TM or stair climber,or, upper leg ergometer. Study 4: There was no difference at 4 wk: Increase of VO_2peak between 4 wk and 6 mo was significant within HIIT and between HIIT and MCT. The participant attended additional sessions with various intensity at the center with their choice. Exercise was performed at center for 4 wk and at home for 6 mo. Study 5: TM¹ means TM or aerobic exercise. AP: Angina pectoris; bike: Cycle ergometer; Cont: Continuous; CABG: Coronary artery bypass graft; CAD: Coronary artery disease; TM: Treadmill; HIIT: High-intensity interval training; HR_peak: Peak heart rate; HRR: Heart rate reserve; MCT: Moderate-intensity continuous training; PPO: Peak power output; RCP: Respiratory compensation point; VAT: Ventilator anaerobic threshold; VO2R: VO₂ reserve; WRp: Peak work rate.

Table 3 Mode, intensity, and VO_2peak increment in high-intensity interval training versus moderate-intensity continuous training (congestive heart failure or diastolic dysfunction) in randomized

Study	Published yr	Sample	n	HIIT	MCT	Duration	Mode	VO2peak pre		VO2peak %increase
								HIIT	MCT	HIIT (%)	MCT (%)
1 Dimo-poulos et al[24]	2006	CHF	24 (HIIT = 10)	3 d/wk, 30 seconds@100% WRp, 30 s rest	3 d/wk, 40 mins@50%WRp	36 sessions	bike	15.4	15.5	7.8	5.8
2 Wisloff et al[22]	2007	CHF, Post MI	27 (HIIT = 9)	3 d (2 d supervised)/wk 4 × 4 min @90%-95%HRpeak, 3 min active recovery 50%-70% HRpeak, total 38 min	3 d (2 d supervised)/wk, 47 min@70%-75% HRpeak, isoload to HIIT	12 wk	TM	13	13	46a	14
3 Roditis et al[46]	2007	CHF	21 (HIIT = 11)	3 d/wk 30 secc @WRpeak 30 s rest, total of 40 min	3 d/wk 40 min@50%WRpeak, equal to total work of HIIT	36 sessions	bike	14.2	15.3	8.5	8.5
4 Smart et al[47]	2012	CHF (LVEF< 35%)	20 (HIIT = 10)	3 d/wk 30 × 1 min @70% VO2peak, 1 min recovery	3 d/wk 30 min@70%VO2peak, same absolute volume of work	16 wk	bike	12.2	12.4	21	13
5 Freyssin et al[26]	2012	CHF (LVEF< 40%)	26 (HIIT = 12)	5 d/wk 12 × 30 sec@50% (4 wk) + 80% (4 wk) of maximum powerb 1 min @ complete rest	5 d/wk 45 min@HRVT1c	8 wk	Bike (HIIT), bike + TM (MCT)	10.7	10.8	27.1a	1.9
6 Fu et al[44]	2013	CHF (LVEF≦40%) NYHA II, III	45 (HIIT = 15)	3 d/wk 5 × 3 min@80%VO2peak 3 min recovery@40% VO2peak	3 d/wk 60 min @60% VO2peak, isoload to Int	12 wk	bike	16	15.9	22.5b	0.6
7 Iellamo et al	2013	CHF with OMI (LVEF< 40%)	20 (HIIT = 10)	2-5 d/wk 2-4 × 4 min@75%-80%HRR, 3 min active pause walk@45%-50%HRR	2-5 d/wk 30-45 min @45%-60%HRR, equated training load (TRIMPi)	12 wk	TM	18.7	18.4	8 22	4 22
8 Hollekim-Strand et al[20]	2014	diastolic dysfunction with Diabetes mellitus	37 (HIIT = 20)	3 d/wk 4 × 4 min @90%-95%HRpeak, total 40 min	Current guideline 10 min/bout 210 min/wk)	12 wk, Home-based thereafter	unknown	31.5	33.2	13.0a	3.6
9 Angadi et al[25]	2015	CHF with preserved EF	15 (HIIT = 9)	3 d/wk 4 × 4 min @85%-90%HRpeak, 3 min active recovery	3 d/wk 30 min@70%HRpeak	4 wk		19.2	16.9	9.4a	0
10 Ellingsen et al[45]	SMARTex-HF, 2017	Stable CHF (NYHA2-3) EF≦35%	200 (3 arms) (HIIT=77)	25 sessions 4 × 4 min@90%-95% HRpeak, 3 min active recovery 50%-70% HRpeak total 38 min	25 sessions, 47 min@60-70%HRpeak	12 wk	bike or TM	0.9	1.1	5.4	6.8
11 Suchy C et al	OptimEX-CLIN, Ongoing	HFpEF	180 (HIIT 60)	3 d/wk 4 × 4 min@ 90%-95% HR peak, 3 min active recovery 50%-70% HRpeak, total 38 min	5 d/wk 40 min@60%-70%HRpeak	3, 12 mo, home-based after 3 mo	bike	?	?	?	?

Controlled Trials Adapted from Ito S et al. Internal Medicine. 2016; 55: 2329-2336.

^a in pre VO_2peak % increase raw: There is significant difference in % increase of VO_2peak between HIIT and MCT. Study 5: ^b each training session consisted of 3 series (12 repetitions of 30 s of exercises, separated by 5 minutes of rest); ^c half of the MCT was on a treadmill and half on a bike. Study 6: ^b pre versus post (not between groups). Study 7: Study hypothesis is similar adaptation in HIIT and MCT. Study 9: ^a evaluated by standardized effect size (d = 0.94) Bike: Cycle ergometer; CAD: Coronary artery disease; CHF: Congestive heart failure; EF: Ejection fraction; HR_peak: Peak heart rate; HIIT: High intensity interval training; HRVT1: Heart rate at the first ventilator threshold; HRR: Heart rate reserve; LVEF: Left ventricular ejection fraction; MCT: Moderate-intensity continuous training; MI: Myocardial infarction; min, minute; NYHA: New York Heart Association; RCP: Respiratory compensation point; VAT: Ventilator anaerobic threshold; PPO: Peak power output; TM: Treadmill; VO2R: VO2 reserve; VT1: First ventilator threshold; WRp: Peak work rate.

Table 4 High-intensity interval training (HIIT) protocol and superiority of HIIT to moderate-intensity continuous training in VO_2peak improvement

	Protocol	No. of study	More improvement of VO2peak in HIIT than in MCT
Coronary artery disease	10 × 1 min	1	0/1
	8 × 2 min	1	1/1
	7 × 3 min	1	0/1
	4 × 4 min	7	5/7 (70.2%)
Chronic heart failure	40 × 30 s	3	1/3
	30 × 1 min	1	0/1
	5 × 3 min	1	1/1
	4 × 4 min	6	3/4 (75%)
			56% (5/9) 2 studies ongoing

Randomized controlled trials comparing improvement of VO_2peak after exercise between HIIT and MCT in patients with CAD or CHF are shown. The protocols of HIIT and incidence of superiority of HIIT to MCT in each protocol are shown. In both groups 4×4 min was most frequently used showing positive rate 70.2% in the coronary artery disease group and 75% in the chronic heart failure group. The other protocols with 30 s, 2 min, and 3 min exercise duration are also effective in the limited number of studies. HIIT: High-intensity interval training; MCT: Moderate-intensity continuous training; CAD: Coronary artery disease; CHF: Chronic heart failure.