Research results from CERG
Here we present the results from our newest publications – and from publications where our researchers have contributed.
Studies published in 2018
- What kind of exercise does older adults prefer?
- Also heart patients with 100 PAI live longer
- Should individuals with atrial fibrillation exercise?
- Which older adults are more likely to drop out of an exercise program?
- Does weather influence physical activity in the elderly?
- Can physical activity prevent atrial fibrillation?
- Can exercise prevent newborns' cardiac dysfunction following obese pregnancies?
- Exercise is linked to less dementia-related death
- The fit and happy live longer
- Heart patients live longer if they stay physically active over time
- Heart failure: Higher increase in oxygen uptake following high intensity interval training
- Effective high intensity interval training in obese children
- Rats escaped atrial fibrillation following high intensity interval training
- Should heart patients exercise the day before surgery?
- Obese children strengthen week hearts by exercising
- Why do failing hearts struggle during strenous acitivty?
More than half of the self-reported activity among participants in the moderate intensity exercise group of the Generation 100 Study was performed as walking. Walking was also the most popular activity among the participants in the high intensity exercise group, but these participants did more cycling and jogging compared to the moderate group. Moreover, the findings show that older adults are able to perform high intensity exercise without strict supervision.
Both groups preferred to exercise outdoors, and only one third of the sessions were performed indoors. We also found that women more often than men exercised together with others. The information is gathered from exercise diaries from the first year of the Generation 100 Study, and includes almost 70 000 exercise logs in total.
Also persons with cardiovascular disease should aim for 100 PAI to live longer. PAI is short for Personal Activity Intelligence, and we have previously shown that those who achieve 100 PAI or more every week live for an average of almost five years longer than others. Our new restults show that this is also true for heart and stroke patients.
We estimated PAI in more than 3000 participants who reported previous myocardial infarction, angina or stroke in the HUNT1 Study, and followed them for up to 30 years. Those who achieved 100 PAI or more had 36 % lower risk of dying from cardiovascular causes compared to inactive patients. They also lived for an average of five years longer than those who earned less than 100 PAI. To achieve 100 PAI was a better predictor of future health benefits than achieving today's exercise recommendations.
Individuals with atrial fibrillation should have individualized exercise based on an evaluation of underlying conditions. Together with colleagues at Bærum hospital, we sum up the current evidence on exercise effects in persons with atrial fibrillation.
One observational registry study shows that persons with atrial fibrillation live longer if they exercise regularly. Moreover, six smaller studies show beneficial effect of three months exercise on physical capacity, burden of atrial fibrillation and quality of life. There is a lack of data on safety of exercise and exercise in athletes with atrial fibrilllation.
Less than 15 % of the 1500 participants dropped out of the Generation 100 study during the first three years. Low education, low grip strenght, low cardiorespiratory fitness and low levels of physical activity were significant predictors of dropping out. Participants with reduced memory status were also more likely to drop out. The results give important information about potential factors that increase the risk for dropping out of long-term exercise programs in older adults..
The Generation 100 study aims to find out if exercise can give older adults longer and healthier lives. The participants are randomized to three group, of which two are exercise groups. Our results also show that participants randomized to exercise – and thus more regular follow-up appointments – aslo were more likely to drop out than those randomized to the control group.
Unfit older adults are less physically active during rain or snow, whereas fit older adults don't seem to let precipitation influence activity levels. Moreover, older adults are more physically active with increasing temperatures. The findings suggest that bad weather might be a barrier towards physical activity in unfit older adults.
To find these results, we studied accelerometer data from 1291 participants in the Generation 100 study. Hour-to-hour data on temperature and precipitation were collected from the Norwegian Meteorological Institute.
Obese and inactive persons had almost double the risk of atrial fibrillation compared to those who were normal weight and highly physically active. On the other hand, the risk was only increased by approximately 50 % in those who were obese and active. Thus, it looks like physical activity modifies the risk of atrial fibrillation in obese individuals.
We included more than 43 000 Norwegian men and women who participated in the third wave of the Nord-Trøndelag Health study between 2006 and 2008. By 2015, almost 1500 of them had a confirmed diagnosis of atrial fibrillation collected from hospital registers. Increasing levels of physical activity were linked to gradually lower risk of atrial fibrillation. Further analysis showed that this was especially true for obese persons.
In this study, exercise during pregnancy did not significantly prevent impaired cardiac function in newborns of obese women. There was, however, a small but consistent tendency towards slightly better cardiovascular measures in the exercise group. Thus, the reason for the lack of significant effects could be that many of the women exercised less than we asked them to, and that the study included quite few women.
55 women with a pre-pregnancy BMI of at least 28 kg/m2 participated in the trial, and half of them were randomized to four weekly exercise sessions consisting of both moderate intensity endurance and strength training from gestational week 14 and throughout pregnancy. However, the women only exercised for a mean of two times a week. Children in both groups were born with weaker hearts than newborns of normal weight mothers.
Physical activity seems to protect against demetia-related mortality both in persons with and without symptoms of anxiety or depression. We followed 37,000 Norwegians for up to 20 years, and exercise with high intensity was linked to the lowest risk of dying of or with dementa during follow-up. Among those who reported several symptoms of psychological distress, regular high-intensity activity was assoicated with less than half the risk of dementia-related death.
The study includes middle-aged and older women and men from seven of the largest population-based studies performed in Norway between 1994 and 2002. In total, more than 900 of the participants died of or with dementia before 2015.
Read the full article in Frontiers in Aging Neuroscience:
Leisure-time physical activity is associated with reduced risk of dementia-related mortality in adults with and without psychological distress: The Cohort of Norway
To stay fit and avoid depressive symptoms could be of great importance for health. Participants who maintained high fitness and reported low symptoms of depression over time had the lowest risk of dying during follow-up. The study is based on information from more than 15,000 middle-aged women and men from the Nord-Trøndelag Health Study.
We used our Fitness Calculator to estimate fitness for all participants. Those who had high fitness and low symptoms of depression at both the two surveys they attended had only half the risk of dying during seven years of follow-up, compared to thos who reported persistently high levels of depressive symptoms and had low estimated fitness over time. Fit persons who improved symptoms of depression from the first to last survey also had reduced risk of early death.
Heart patients live longer if they are physically active over time, whereas weight loss is not associated with reduced risk of premature death. Sustained physical activity according to guidelines seems to be particularly protective against deadth from all causes and cardiovascular disease, compared to staying physically inactive.
The results are based on The Nord Trøndelag Health Study, and we followed more than 3,300 heart patients for up to 30 years. All of them had a previous heart attack or angina, and participated in at least two health surveys between 1984 and 2008. Those who stayed physically active over time had the lowest risk of dying during follow-up, but also those who went from being inactive to sufficiently physically active had reduced risk.
High intensity interval training improves cardiorespiratory fitness mer in patients with heart failure than moderat exercise. A new meta-analysis of 13 trials has compared the two modes of exercise for patients with heart failure and reduced ejection fraction. Quality of life improved similarly with moderate and high intensity training.
CERG's Professor Øyvind Ellingsen helped Brazilian researchers with the review. The analysis includes trials with several different modes of high intensity interval training, with intervals ranging from 30 seconds to 15 minutes duration. When the researchers compared isocaloric protocols only, high intensity interval training was no longer significantly superior to moderate continous training.
Read the full article in International Journal of Cardiology:
High intensity interval training versus moderate intensity continuous training on exercise capacity and quality of life in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis
Both 4x4 interval training and continuous training with moderate intensity for three months improved cardiorespiratory fitness inn obese children. However, high intensity training was most effective.
99 obese children participated in the study. They were aged between seven and 16, og randomly allocated to three groups. All the children and their families were given nutritional advice, and the children in two groups exercised either 4x4 intervals or continuously at at more moderate intensity. Exercise had no effect on body weight or several other traditional risk factors for cardiovascular disease.
Aerobic interval training prevents susceptibility to atrial fibrillation in middle-aged rats. Sustained atrial fibrillation was not induced in any of the 14 rats who exercised for 16 weeks, compared to four of the eleven rats who did not exercise.
We compared middle-aged rats who exercised for 16 weeks with both young and middle-aged rates who did not exercise. After the exercise intervention, the middle-aged rats had the same aerobic fitness as young, sedentary rats. We also examined the rat hearts, and found that exercise had increased the atrial conduction velocity, which could explain the reduced vulnerability to atrial fibrillation.
One bout of exercise 24 hours before cardiac surgery does not protect the heart, and might actually be harmful. Compared to no exercise, exercise increased the levels of a marker related to programmed cell death in the heart prior to surgery, and also reduced the function of the energy-producing mitochondria after surgery.
Acute exercise as preconditioning before surgery has shown promising results in rats, and we wanted to investigate if exercise just prior to surgery offers cardioprotection in humans as well. Half of the 20 patients in the study performed moderate intensity exercise the day before elective coronary artery bypass grafting at St. Olavs hospital.
Three months of exercise normalized the heart's pump function at rest in obese children! High intensity interval training was even better for the hearts than moderate exercise, but both exercise modalities were more effective than nutrition advice only.
Obese children have reduced heart function compared to their healthy-weight counterparts. Our new results highlight the importance of structured exercise programs, including high intensity interval training, to improve heart health in pediatric obesity. A total of 99 Norwegian and Australian children participated in the trial.
For the first time, we have collected pieces from nine hearts of patients with heart failure after a myocardial infarction, made the pieces beat as fast as hearts do during physical activity, and compared the function with heart pieces from eight stable heart patients without an infarction.
The results show that the function of the failing hearts almost broke down completely as the heart frequency increased. The intracellular calcium handling was severly impaired at high frequencies. Calcium is important for the regulation of contraction as well as relaxation of the cardiomyocytes.
List of scientific publications
Reitlo, L. S., Sandbakk, S. B., Viken, H., Aspvik, N. P., Ingebrigtsen, J. E., Tan, X., Wisløff, U., & Stensvold, D. (2018). Exercise patterns in older adults instructed to follow moderate-or high-intensity exercise protocol–the generation 100 study. BMC Geriatrics, 18(1), 208.
Kieffer, S. K., Zisko, N., Coombes, J. S., Nauman, J., & Wisløff, U. (2018) Personal Activity Intelligence and Mortality in Patients with Cardiovacular Disease: The HUNT Study. Mayo Clinic Proceedings, 92(5), 1191-1201
Myrstad, M., Malmo, V., Ulimoen, S. R., Tveit, A., & Loennechen, J. P. (2018). Exercise in individuals with atrial fibrillation. Clinical Research in Cardiology, 1-8.
Viken, H., Reitlo, L. S., Zisko, N., Nauman, J., Aspvik, N. P., Ingebrigtsen, J. E., Wisløff, D., & Stensvold, D. (2018). Predictors of Dropout in Exercise Trials in Older Adults. Medicine and science in sports and exercise.
Aspvik, N. P., Viken, H., Ingebrigtsen, J. E., Zisko, N., Mehus, I., Wisløff, U., & Stensvold, D. (2018). Do weather changes influence physical activity level among older adults?–The Generation 100 study. PloS one, 13(7), e0199463.
Garnvik, L. E., Malmo, V., Janszky, I., Wisløff, U., Loennechen, J. P., & Nes, B (2018). Physical activity modifies the risk of atrial fibrillation in obese individuals: The HUNT3 study. European Journal of Preventive Cardiology. 2047487318784365
Nyrnes, S. A., Garnæs, K. K., Salvesen, Ø., Timilsina, A. S., Moholdt, T., & Ingul, C. B. (2018). Cardiac function in newborns of obese women and the effect of exercise during pregnancy. A randomized controlled trial. PloS one 13(6): e0197334
Zotcheva, E., Selbæk, G., Bjertness, E., Ernstsen, L., & Strand, B. H. (2018). Leisure-time physical activity is associated with reduced risk of dementia-related mortality in adults with and without psychological distress: The Cohort of Norway. Frontiers in Aging Neuroscience, 10, 151.
Aamot, I. L., & Rognmo, Ø. (2018) Exercise therapy in intermittent claudication. E-Journal of Cardiology Practice
Carlsen, T., Salvesen, Ø., Sui, X., Lavie, C. J., Blair, S. N., Wisløff, U., & Ernstsen, L. (2018). Long-term Changes in Depressive Symptoms and Estimated Cardiorespiratory Fitness and Risk of All-Cause Mortality: The Nord-Trøndelag Health Study. Mayo Clinic Proceedings.
Tjønna, A. E., Ramos, J. S., Pressler, A., Halle, M., Jungbluth, K., Ermacora, E., Salvesen, Ø., Rodrigues, J., Bueno jr., C. R., Munk, P. S., Coombes, J., & Wisløff, U. (2018). EX-MET study: exercise in prevention on of metabolic syndrome–a randomized multicenter trial: rational and design. BMC public health, 18(1), 437.
Moholdt, T., Lavie, C. J., & Nauman, J. (2018). Sustained Physical Activity, Not Weight Loss, Associated With Improved Survival in Coronary Heart Disease. Journal of the American College of Cardiology, 71(10), 1094-1101.
Neto, M. G., Durães, A. R., Conceição, L. S. R., Saquetto, M. B., Ellingsen, Ø., & Carvalho, V. O. (2018). High intensity interval training versus moderate intensity continuous training on exercise capacity and quality of life in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis. International Journal of Cardiology.
Dias, K. A., Ingul, C. B., Tjønna, A. E., Keating, S. E., Gomersall, S. R., Follestad, T., Hosseini, M. S., Hollekim-Strand, S. M., Ro, T. B., Haram, M., & Huuse, E. M., Davies, P. S. W., Cain, P. A., Leong, G. M., & Coombes, J. S. (2017). Effect of High-Intensity Interval Training on Fitness, Fat Mass and Cardiometabolic Biomarkers in Children with Obesity: A Randomised Controlled Trial. Sports Medicine, 1-14.
Malmo, V., Kelly, A., Stolen, T., Garten, K. S., Rolim, N., Wisløff, U., Smith, G., & Loennechen, J. P. (2018). Aerobic interval training prevents age-dependent vulnerability to atrial fibrillation in rodents. Frontiers in Physiology, 9, 206.
Ingul, C. B. (2018). Low volume, high intensity: Time-efficient exercise for the treatment of hypertension. European Journal of Preventive Cardiology, 2047487318760040.
Smenes, B. T., Bækkerud, F. H., Slagsvold, K. H., Hassel, E., Wohlwend, M., Pinho, M., Høydal, M., Wisløff, U., Rognmo, Ø., & Wahba, A. (2018). Acute exercise is not cardioprotective and may induce apoptotic signalling in heart surgery: a randomized controlled trial. Interactive cardiovascular and thoracic surgery.
Ingul, C. B., Dias, K. A., Tjonna, A. E., Follestad, T., Hosseini, M. S., Timilsina, A. S., Hollekim-Strand, S. M., Ro, T. B., Davies, P. S. W., Leong, G. M., & Coombes, J. S. (2018). Effect of High Intensity Interval Training on Cardiac Function in Children with Obesity: a Randomised Controlled Trial. Progress in Cardiovascular Diseases.
Høydal, M. A., Kirkeby‐Garstad, I., Karevold, A., Wiseth, R., Haaverstad, R., Wahba, A., Stølen, T., L. Contu, R., Condorelli, G., Ellingsen, Ø., Smith, G. L., Kemi, O. J., & Wisløff, U. (2018). Human cardiomyocyte calcium handling and transverse tubules in mid‐stage of post‐myocardial‐infarction heart failure. ESC heart failure.
Williams, C. J., Williams, M. G., Eynon, N., Ashton, K. J., Little, J. P., Wisloff, U., & Coombes, J. S. (2017). Genes to predict VO 2max trainability: a systematic review. BMC genomics, 18(8), 831.
Stensvold, D., Sandbakk, S. B., Viken, H., Zisko, N., Reitlo, L. S., Nauman, J., Gaustad, S. E., Hassel, E., Moufack, M., Brønstad, E., Aspvik, N. P., Malmo, V., Steinshamn, S. L., Støylen, A., Anderssen, S. A., Helbostad, J. L., Rognmo, Ø, & Wisløff, U. (2017). Cardiorespiratory Reference Data in Older Adults: The Generation 100 Study. Medicine and science in sports and exercise, 49(11), 2206.
Bowen, T. S., Brauer, D., Rolim, N. P., Bækkerud, F. H., Kricke, A., Berre, A. M. O., Fischer, T., Linke, A., da Silva G. J., Wisløff, U., & Adams, V. (2017). Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection Fraction. Journal of the American Heart Association, 6(10), e006416.
Mallard, A. R., Hollekim-Strand, S. M., Coombes, J. S., & Ingul, C. B. (2017). Exercise intensity, redox homeostasis and inflammation in type 2 diabetes mellitus. Journal of science and medicine in sport, 20(10), 893-898.
Zaglia, T., Ceriotti, P., Campo, A., Borile, G., Armani, A., Carullo, P., Prando, V., Coppini, R., Vida, V., Stølen, T., Wisløff, U., Cerbai, E., Stellin, G., Faggian, G., De Stefani, D., Sandri, M., Rizzuto, R., Di Lisa, F., Pozzan, T., Catalucci, D., & Mongillo, M. (2017). Content of mitochondrial calcium uniporter (MCU) in cardiomyocytes is regulated by microRNA-1 in physiologic and pathologic hypertrophy. Proceedings of the National Academy of Sciences, 201708772.
Wisloff, U., & Lavie, C. J. (2017). Taking Physical Activity, Exercise, and Fitness to a Higher Level. Progress in cardiovascular diseases, 60(1), 1.
Wisløff, U., Lavie, C. J., & Rognmo, Ø. (2017). Letter by Wisløff et al Regarding Article,“High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction”. Circulation, 136(6), 607-608.
Leinan, I. M., Aamot, I. L., Støylen, A., Karlsen, T., & Wisløff, U. (2015). Upper arm venous compliance and fitness in stable coronary artery disease patients and healthy controls. Clinical physiology and functional imaging.
Martins C, Aschehoug I, Ludviksen M, Holst J, Finlayson G, Wisloff U, Morgan L, King N, Kulseng B. (2017). High-Intensity Interval Training, Appetite, and Reward Value of Food in the Obese. Medicine & Science in Sports & Exercise 49(9):1851-1858
D'Souza, A., Pearman, C. M., Wang, Y., Nakao, S., Logantha, S. J. R., Cox, C., Bennett, H., Zhang., Y., Johnsen, A. B., Linscheid, N., Poulsen, P. C., Elliott, J., Coulson, J., McPhee, J., Robertson, A., da Costa Martins, P. A., Kitmitto, A., Wisløff, U., Cartwright, E. J., Monfredi, O., Lundby, A., Dobrzynski, H., Ocaendy, D., Morris, G. M., & Boyett, M. R. (2017). Targeting miR-423-5p Reverses Exercise Training-Induced HCN4 Channel Remodeling and Sinus Bradycardia. Circulation research, CIRCRESAHA-117.
Dias, K. A., Masterson, C. E., Wallen, M. P., Tjonna, A. E., Hosseini, M. S., Davies, P. S., Cain, P. A., Leong, G. M., Arena, R., Ingul, C. B., & Coombes, J. S. (2017). Assessment of the 5-Minute Oxygen Uptake Efficiency Slope in Children With Obesity. Pediatric exercise science, 29(3), 350-360.
Dias, K. A., Spence, A. L., Sarma, S., Oxborough, D., Timilsina, A. S., Davies, P. S., Cain, P. A., Leong, G. M., Ingul, C. B., & Coombes, J. S. (2017). Left ventricular morphology and function in adolescents: Relations to fitness and fatness. International journal of cardiology, 240, 313-319.
Silva, G. J., Bye, A., el Azzouzi, H., & Wisløff, U. (2017). MicroRNAs as important regulators of exercise adaptation. Progress in cardiovascular diseases, 60(1), 130-151.
Sandbakk, S. B., Nauman, J., Lavie, C. J., Wisløff, U., & Stensvold, D. (2017). Combined Association of Cardiorespiratory Fitness and Body Fatness With Cardiometabolic Risk Factors in Older Norwegian Adults: The Generation 100 Study. Mayo Clinic Proceedings: Innovations, Quality & Outcomes, 1(1), 67-77.
Karlsen, T., Aamot, I. L., Haykowsky, M., & Rognmo, Ø. (2017). High Intensity Interval Training for Maximizing Health Outcomes. Progress in Cardiovascular Diseases.
Zisko, N., Skjerve, K. N., Tari, A. R., Sandbakk, S. B., Wisloff, U., Nes, B. M., & Nauman, J. (2017). Personal Activity Intelligence (PAI), Sedentary Behavior and Cardiovascular Risk Factor Clustering-The HUNT Study. Progress in Cardiovascular Diseases.
Nauman, J., Tauschek, L. C., Kaminsky, L. A., Nes, B. M., & Wisløff, U. (2017). Global fitness levels: findings from a Web-based surveillance report. Progress in Cardiovascular Diseases.
Schaardenburgh, M., Wohlwend, M., Rognmo, Ø., & Mattsson, E. J. (2017). Exercise in claudicants increase or decrease walking ability and the response relates to mitochondrial function. Journal of translational medicine, 15(1), 130.
Morland, C., Andersson, K. A., Haugen, Ø. P., Hadzic, A., Kleppa, L., Gille, A., Rinholm, J. E., Palibrk, V., Diget, E. H., Kennedy, L. H., Stølen, T., Hennestad, E., Moldestad, O., Cai, Y., Puchades, M., Offermanns, S., Vervaeke, K., Bjørås, M., Wisløff, U., Storm-Mathisen, J., & Bergersen, L. H., (2017). Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1. Nature Communications, 8.
Zisko, N., Nauman, J., Sandbakk, S. B., Aspvik, N. P., Salvesen, Ø., Carlsen, T., Viken, H., Ingebrigtsen, J. E., Wisløff, U., & Stensvold, D. (2017). Absolute and relative accelerometer thresholds for determining the association between physical activity and metabolic syndrome in the older adults: The Generation-100 study. BMC geriatrics, 17(1), 109.
Karlsen, T., Nauman, J., Dalen, H., Langhammer, A., & Wisløff, U. (2017, May). The Combined Association of Skeletal Muscle Strength and Physical Activity on Mortality in Older Women: The HUNT2 Study. In Mayo Clinic Proceedings (Vol. 92, No. 5, pp. 710-718). Elsevier.
Bowen, T. S., Aakerøy, L., Eisenkolb, S., Kunth, P., Bakkerud, F., Wohlwend, M., Berre, A. M. O., Fischer, T., Wisløff, U., Schuler, G., Steinshamn, S., Adams, V, & Brønstad, E., (2017). Exercise Training Reverses Extrapulmonary Impairments in Smoke-exposed Mice. Medicine and science in sports and exercise, 49(5), 879-887.
Østhus, I. B. Ø., Lydersen, S., Dalen, H., Nauman, J., & Wisløff, U. (2017). Association of Telomere Length With Myocardial Infarction: A Prospective Cohort From the Population Based HUNT 2 Study. Progress in Cardiovascular Diseases.
Van Schaardenburgh, M., Wohlwend, M., Rognmo, Ø., & Mattsson, E. (2017). Calf raise exercise increases walking performance in patients with intermittent claudication. Journal of vascular surgery, 65(5), 1473-1482.
Hassel, E., Stensvold, D., Halvorsen, T., Wisløff, U., Langhammer, A., & Steinshamn, S. (2017). Lung function parameters improve prediction of VO2peak in an elderly population: The Generation 100 study. PloS one, 12(3), e0174058.
Ljones, K., Ness, H. O., Solvang-Garten, K., Gaustad, S. E., & Høydal, M. A. (2017). Acute exhaustive aerobic exercise training impair cardiomyocyte function and calcium handling in Sprague-Dawley rats. PloS one, 12(3), e0173449.
Nes, B. M., Gutvik, C. R., Lavie, C. J., Nauman, J., & Wisløff, U. (2017). Personalized activity intelligence (PAI) for prevention of cardiovascular disease and promotion of physical activity. The American journal of medicine, 130(3), 328-336.
Ellingsen, Ø., Halle, M., Conraads, V., Støylen, A., Dalen, H., Delagardelle, C., Larsen, A-I., Hole, T., Mezzqani, A., van Craenenbroeck E. M., Videm, V., Beckers, P. J., Christie, J. W., Winzer, E. B., Mangne, N., Woitek, F., Höllriegel, R., Pressler, A. P., Monk-Hansen, T., Snoer, M., Feiereisen, P., Valborgland, T., Kjekshus, J. K., Hambrecht, R., Gielen, S., Karlsen, T., Prescott, E. B. & Linke, A. (2017). High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction. Circulation, 135(9), 839-849.
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