Exercise as a modality to improve heart transplantation-related functional impairments: An article review

Table 1 Summary of exercise protocols in heart transplantation recipients

Ref.	Exercise intervention	Exercise protocol
		Frequency	Intensity and time	Type	Warm-up	Cool-down	Program duration
Torto et al[53], 2022	Single-leg vs double-leg HIIT	3 sessions per week	Two kinds of HIIT, done alternately. 4-min exercise bouts at high intensity alternated by 3-min rest at low intensity, 4 sets, 12 bouts. 2-min exercise bouts at high intensity alternated by 2-min rest at low intensity, 6 sets, 12 bouts	Ergocycle, pedaling frequency 60-75 RPM	5 min	5 min	8 wk
Rustad et al[40], 2014	HIIT vs usual exercise	3 sessions per week	4-min exercise bouts at 85%-95% of HR peak alternated by 3-min rest equal to Borg scale of 11-13, 4 bouts	Treadmill uphill walking or running	10 min		3 episodes of 8-wk exercise
Dall et al[15], 2014	HIIT vs MICT	3 sessions per week	HIIT: 4-, 2-, and 1-min bouts of exercise at > 80% of VO2 peak alternated by a 2-min rest at 60% of VO2 peak, 32 min	Ergocycle	10 min	10 min	12 wk
			MICT; 60%-70% of VO2 peak, 45 min
Yardley et al[14], 2017	HIIT vs usual care	3 sessions per week	4-min exercise bouts at 85%–95% of HR max alternated by 3-min active recovery periods equal to Borg scale of 11–13, 4 bouts	Treadmill or ergocycle	10 min	10 min	12 mo
Nytrøen et al[51], 2012	HIIT vs usual care	3 sessions per week	4-min exercise bouts at 85%–95% of HR max alternated by 3-min active recovery periods equal to Borg scale of 11–13, 4 bouts	Treadmill	10 min		3 episodes of 8-wk exercise
Hermann et al[43], 2011	HIIT vs no exercise	3 sessions per week	Initial HIIT 4-min, 2-min, 30-s exercise bouts at 80%, 85%, and 90% of VO2 peak consecutively, equal to Borg scale of 18–19, followed by half a minute of recovery period. After HIIT, 10-min staircase running with an intensity of 80% of VO2 peak. Total time: 42 min	Bicycle and staircase running	10 min	10 min	8 wk
Nytrøen et al[16], 2012	HIIT vs MICT and no exercise	3 sessions per week	HIIT: Exercise bouts at 85%-95% of peak effort	Treadmill			9 mo
			MICT: Exercise bouts at 60%-80% of peak effort
Haykowsky et al[41], 2009	Aerobic and strengthening exercises	Aerobic: 5 sessions per week during the first 8 wk. 3 sessions per week during the final 4 wk	Aerobic: During the first 8 wk: Exercise at HR equal to 60%-80% of VO2 peak for 30-45 min During the final 4 wk: Exercise at HR equal to 80% of VO2 peak for 45 min	Ergocycle			12 wk
		Strengthening: 2 sessions per week	Strengthening: 50% of maximal strength, 1-2 sets, 10-15 repetitions	Chest press, arm curls, latissimus dorsi pulldown, and leg press
Karapolat et al[42], 2008	Flexibility, aerobic, strengthening, breathing, and relaxation exercises	3 sessions per week, 1.5 h exercise per session	Flexibility: Stretching and range of motion exercise	Applied to the trunk, upper extremities, and lower extremities joints			8 wk
			Aerobic: Exercise at 60%-70% of the VO2 peak equal to a Borg scale of 13-15, 30 min	Treadmill or ergocycle
			Strengthening: Lightweight of 250-500 g, 2 wk after performing aerobic exercise	Abdominal, upper extremities, and lower extremities muscle groups
				Pursed-lip breathing, synchronization of thoracic and abdominal movement, and expiratory abdominal augmentation
				Jacobson’s progressive muscle relaxation
Hsu et al[52], 2011	Hospital-based-aerobic exercise	3 sessions per week	Exercise at 50%-80% of VO2 peak, 25-30 min	Combination of ergocycle and treadmill	10 min	10 min	12 wk

HIIT: High-intensity interval training; RPM: Revolutions per minute; HR: Heart rate; MICT: Moderate-intensity continuous training; VO2 peak: Peak oxygen uptake.

Table 2 Summary of research on exercise in heart transplantation recipients

Ref.	Aim(s)	Subjects	Outcomes	Results
Torto et al[53], 2022	To compare the effect of SL HIIT and DL HIIT on pulmonary VO2 and HR kinetics in three groups of transplanted patients	33 subjects underwent heart, kidney, and liver transplantation	Pulmonary VO2; HR kinetic; Exercise capacity	During moderate-intensity exercise: SL and DL were effective in improving pulmonary VO2 and HR kinetics; No difference between SL and DL in pulmonary VO2 and HR kinetics; During heavy–intensity exercise, SL was as effective as DL in improving exercise capacity
Rustad et al[40], 2014	To investigate the effect of HIIT on exercise capacity and cardiac function	52 subjects, 1-8 years after heart transplantation randomized equally to the exercise group (EG) and control group (CG)	Exercise capacity; Cardiac function (systolic and diastolic) was determined by echocardiography	HIIT effectively improved exercise capacity; No clinically important improvement in systolic and diastolic functions with HIIT
Dall et al[15], 2014	To compare the effect of HIIT on VO2 peak, BP, HR rest, HR peak, HR recovery, HR reserve, and workload during exercise test	17 adult stable HT recipients (≥ 12 mo after HT) were randomized into HIIT and CON	Primary outcome: VO2 peak; Secondary outcomes: BP, HR rest, HR peak, HR recovery, and HR reserve during exercise testing	The effect of HIIT on VO2 peak was superior to CON; Improved HR reserve and HR peak were only found in the HIIT group; Improved HR recovery in both groups; A marked loss of effects after 5 mo
Yardley et al[14], 2017	To evaluate the continuity of HIIT and maintenance of exercise benefits on physical capacity long term after the intervention ended	41 stable heart transplant recipients who underwent 12-mo HIIT were followed until 5 years	Physical activity; Physical capacity; Exercise variables; Muscular exercise capacity; Body composition and metabolic profile; HRQoL; Depression and anxiety	Both groups maintained moderate physical activity levels after 5 years; Both groups demonstrated equal aerobic performance and daily activities after 5 years; HIIT was associated with a significant increase in VO2 peak after 1 year and a smaller decline in VO2 peak after 5 years; No difference between the two groups at 5-year follow-up in decreased VO2 peak; There was a non-clinically significant increase in VE/VCO2 slope in the HIIT group after 5 years; No difference in muscular exercise capacity between the two groups after 5 years; HRQoL score was good and prevalence of depression was low in both groups after 5 years; Long-term anxiety symptoms was reduced in the HIIT group
Nytrøen et al[51], 2012	To prove that HIIT would improve VO2 peak with a higher percent of predicted than previously shown in most studies; To investigate possible peripheral and central mechanisms behind an increase in VO2 peak	52 stable heart transplant recipients were randomized into HIIT and control groups	VO2 peak; Muscle strength and muscular exercise capacity; Body composition; HRQoL	VO2 peak was significantly improved in the HIIT group and no changes in the control group. A predicted VO2 peak level of 89% was achieved and higher than previous studies; Muscular exercise capacity was significantly improved; No significant difference between groups in changes in body composition at the follow-up; No significant changes in HRQoL sum scores in both groups at the follow-up, but the general health sub-score was significantly different between groups
Hermann et al[43], 2011	To investigate the long-term effect of HIIT on VO2 peak, FMD, BP, inflammation markers, and natriuretic peptide in HT recipients	30 HT recipients at 12 mo of transplantation were randomized into exercise and control groups	VO2 peak; FMD; BP; Inflammation markers; Natriuretic peptide	VO2 peak and FMD increased significantly in the HIIT group compared to the control group; No correlation was noted between BP reduction and improvement in FMD in the HIIT group; CRP was significantly decreased in the HIIT group while there was no change in the control group; TNF-alpha and IL-6 concentrations were unchanged in both groups; No significant decrease in pro-BNP and a significant decrease in pro-ANP in the HIIT group; No change in the natriuretic peptide concentration in the control group
Nytrøen et al[16], 2012	To report the effect of HITT vs MICT or no exercise among young HT recipients	28 young subjects (< 40 years) from the previous two studies	The primary outcome was VO2 peak; Secondary outcomes were maximum muscle strength and muscular endurance	HIIT vs MICT: Increased VO2 peak and maximum muscle strength were higher in HIIT than MICT after 1 year; No significant difference between the two groups in muscular exercise capacity
				HIIT vs no exercise: Increased VO2 peak and maximum muscle strength were higher in HIIT compared to the no exercise group; No significant difference between the two groups in muscular exercise capacity
Haykowsky et al[41], 2009	To investigate the effect of supervised aerobic exercise combined with strength training (SET) vs control with no training (NT) on VO2 peak, peripheral vascular function, LV systolic function, maximum strength, and lean mass in stable HT recipients	43 stable HT recipients at 0.5 years or more post-surgery were randomized into two groups	Primary outcome: VO2 peak; Secondary outcomes: Brachial artery endothelial function, LV systolic function, maximum strength, and lean mass	VO2 peak and peak power output were higher in SET than in NT; LV systolic function was not different after intervention in both groups; Endothelial-independent or -dependent vasodilation was unchanged in both groups; Chest- and leg-press maximum strength was significantly increased after SET and no change in arm curl strength or latissimus dorsi pulldown; The lean mass of the leg was significantly higher after SET than NT
Karapolat et al[42], 2008	To explore the effects of home-based (Group 1) and hospital-based exercise (Group 2) on chronotropic variables and exercise capacity in HT recipients	42 subjects, randomized into two groups	Exercise capacity; Metabolic function; Chronotropic variables (chronotropic response and HR recovery)	Group 1: A significant difference in post-exercise VO2 peak and metabolic function; The difference between HR reserve pre- and post-exercise was significant; No significant differences in other chronotropic variables
				Group 2: No significant change in all outcomes after the exercise
Karapolat et al[44], 2013	To investigate the effects of CR on pulmonary functions, exercise capacity, HRQoL, and psychological state of HF, HT, or LVAD patients	46, 40, and 11 subjects diagnosed with end-stage HF, HT, and LVAD, respectively	Exercise capacity (VO2 peak); Pulmonary function (PFT); HRQoL (SF-36); Psychological state (BDI) and State-Trait Anxiety Inventory (STAI)	Pre- and post-exercise VO2 peak, pulmonary function test (FEV 1% and FVC%), SF-36, and depressive symptoms were significantly different in all three groups, but the ratio of FEV 1 to FVC was not significantly different; No significant differences in VO2 peak, PFT, SF-36, or BDI scores among the three groups; STAI scores in intergroup and intragroup assessments of the three groups were not significantly different
Rolid et al[45], 2020	To compare effects of HIIT and MICT on biomarkers, pulmonary function, heart function, VO2 peak, muscle strength, daily PA, symptoms of anxiety and depression, and HRQoL after 1 year and 3 years	78 HT recipients completed 1-year follow-up and 65 subjects completed 3-year follow-up	Biomarkers; Pulmonary function; Heart function; VO2 peak; Muscle strength; Daily PA; Symptoms of depression and anxiety; HRQoL	Changes in biomarker, pulmonary function, heart function, VO2 peak, daily PA, and mental and physical summary scores were not significantly different between groups from baseline to 3 years; No differences between the two groups from 1 year to 3 years; Both groups had a stable exercise capacity with a small decline in VO2 peak; HIIT group showed a higher change in VO2 peak from baseline to 1 year; Muscle endurance improved significantly from baseline to 1 year and remained significantly higher at 3 years in both groups. An improvement was higher in the HIIT group; The median value of HRQoL in physical and mental components was > 50 in both groups. Physical component scores were changed in both groups, while mental component scores remained high and stable after 3 years. Symptoms of anxiety were low in both groups and no between-group difference from baseline to the 3-year follow-up
Hsu et al[52], 2011	To investigate the effect of the phase 2 CR program on exercise capacity and HRQoL; To test the hypothesis (the peak physical capacity achieved after training is not a major determinant of HRQoL)	45 clinically stable HT recipients and 34 CABG patients who completed a phase II CR	VO2 peak; HRQoL	An early CR program improved VO2 peak and HRQoL significantly; Improvement of HRQoL was greater in the HT group compared to CABG; The relative increase in physical capacity is the major determinant of HRQoL

HIIT: High-intensity interval training; SL: Single-leg; DL: Double-leg; HR: Heart rate; VO2peak: Peak oxygen uptake; BP: Blood pressure, HT: Heart transplantation; CON: Continued moderate exercise; HRQoL: Health-related quality of life; VE/VCO2 slope: Ventilation/carbon dioxide production slope; FMD: Flow-mediated dilation; TNF-α: Tumor necrosis factor-α; IL-6: Interleukin 6; pro-BNP: Pro-brain natriuretic peptide; pro-ANP: Pro-atrial natriuretic; MICT: Moderate-intensity continuous training; SET: Strength and endurance training; NT: No training; LV: Left ventricle; CR: Cardiac rehabilitation; HF: Heart failure; LVAD: Left ventricular assist device; PFT: Pulmonary function test; SF-36: Short-form 36 items; BDI: Beck’s Depression Inventory; STAI: State-Trait Anxiety Inventory; FEV1: Forced expiration volume in one second; FVC: Forced vital capacity; PA: Physical activity; CABG: Coronary artery bypass graft.