Year 2026,
Volume: 4 Issue: 1, 14 - 21, 23.01.2026
Mehmet Fatih Sanver
,
Melda Saglam
,
Ebru Çalık
,
Saadettin Kılıçkap
,
Naciye Vardar Yaglı
References
-
1. Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023;73(3):233-54.
-
2. Islami F, Goding Sauer A, Miller KD, Siegel RL, Fedewa SA, Jacobs EJ, et al. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J Clin. 2018;68(1):31-54.
-
3. Toohey K, Pumpa KL, Arnolda L, Cooke J, Yip D, Craft PS, et al. A pilot study examining the effects of low-volume high-intensity interval training and continuous low to moderate intensity training on quality of life, functional capacity and cardiovascular risk factors in cancer survivors. PeerJ. 2016;4:e2613.
-
4. De Couck M, Gidron Y. Norms of vagal nerve activity, indexed by Heart Rate Variability, in cancer patients. Cancer Epidemiol. 2013;37(5):737-41.
-
5. Koelwyn GJ, Jones LW, Moslehi J. Unravelling the causes of reduced peak oxygen consumption in patients with cancer: complex, timely, and necessary. J Am Coll Cardiol. 2014;64(13):1320-2.
-
6. Bonsignore A, Marwick TH, Adams SC, Thampinathan B, Somerset E, Amir E, et al. Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy. JACC CardioOncol. 2021;3(5):678-91.
-
7. Yoon SY, Oh J. Cardiovascular Autonomic Dysfunction Before and After Chemotherapy in Cancer Patients. J Clin Neurol. 2024;20(6):551-62.
-
8. Lakoski SG, Jones LW, Krone RJ, Stein PK, Scott JM. Autonomic dysfunction in early breast cancer: Incidence, clinical importance, and underlying mechanisms. Am Heart J. 2015;170(2):231-41.
-
9. Bertrand E, Caru M, Lemay V, Andelfinger G, Laverdiere C, Krajinovic M, et al. Heart rate response and chronotropic incompetence during cardiopulmonary exercise testing in childhood acute lymphoblastic leukemia survivors. Pediatr Hematol Oncol. 2021;38(6):564-80.
-
10. Paolillo S, Agostoni P, De Martino F, Ferrazzano F, Marsico F, Gargiulo P, et al. Heart rate during exercise: mechanisms, behavior, and therapeutic and prognostic implications in heart failure patients with reduced ejection fraction. Heart Fail Rev. 2018;23(4):537-45.
-
11. Groarke JD, Tanguturi VK, Hainer J, Klein J, Moslehi JJ, Ng A, et al. Abnormal exercise response in long-term survivors of hodgkin lymphoma treated with thoracic irradiation: evidence of cardiac autonomic dysfunction and impact on outcomes. J Am Coll Cardiol. 2015;65(6):573-83.
-
12. Arab C, Dias DP, Barbosa RT, Carvalho TD, Valenti VE, Crocetta TB, et al. Heart rate variability measure in breast cancer patients and survivors: A systematic review. Psychoneuroendocrinology. 2016;68:57-68.
-
13. Ness KK, Plana JC, Joshi VM, Luepker RV, Durand JB, Green DM, et al. Exercise Intolerance, Mortality, and Organ System Impairment in Adult Survivors of Childhood Cancer. J Clin Oncol. 2020;38(1):29-42.
-
14. Vigo C, Gatzemeier W, Sala R, Malacarne M, Santoro A, Pagani M, et al. Evidence of altered autonomic cardiac regulation in breast cancer survivors. J Cancer Surviv. 2015;9(4):699-706.
-
15. Saglam M, Arikan H, Savci S, Inal-Ince D, Bosnak-Guclu M, Karabulut E, et al. International physical activity questionnaire: reliability and validity of the Turkish version. Percept Mot Skills. 2010;111(1):278-84.
-
16. Azak A, Çınar S. Lenfomalı (hodgkin ve non-hodgkin) hastalarda yorgunluk sendromu ve etkileyen faktörler. Turk J Hematol Oncol. 2005;15:78-83.
-
17. American Thoracic S, American College of Chest P. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003;167(2):211-77.
-
18. Cole CR, Foody JM, Blackstone EH, Lauer MS. Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort. Ann Intern med. 2000;132(7):552-5.
-
19. Lauer MS, Francis GS, Okin PM, Pashkow FJ, Snader CE, Marwick TH. Impaired chronotropic response to exercise stress testing as a predictor of mortality. JAMA. 1999;281(6):524-9.
-
20. Cramer L, Hildebrandt B, Kung T, Wichmann K, Springer J, Doehner W, et al. Cardiovascular function and predictors of exercise capacity in patients with colorectal cancer. J Am Coll Cardiol. 2014;64(13):1310-9.
-
21. Viale PH, Yamamoto DS. Cardiovascular toxicity associated with cancer treatment. Clin J Oncol Nurs. 2008;12(4):627-38.
-
22. Grote S, Ricci JM, Dehom S, Modeste N, Sealy DA, Tarleton HP. Heart Rate Variability and Cardiovascular Adaptations Among Cancer-Survivors Following a 26-Week Exercise Intervention. Integr Cancer Ther. 2020;19.
-
23. Schmid D, Leitzmann MF. Cardiorespiratory fitness as predictor of cancer mortality: a systematic review and meta-analysis. Ann Oncol. 2015;26(2):272-8.
-
24. Wagner LI, Cella D. Fatigue and cancer: causes, prevalence and treatment approaches. Br J Cancer. 2004;91(5):822-8.
-
25. Velthuis MJ, May AM, Koppejan-Rensenbrink RA, Gijsen BC, van Breda E, de Wit GA, et al. Physical Activity during Cancer Treatment (PACT) Study: design of a randomised clinical trial. BMC Cancer. 2010;10:272.
-
26. Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, et al. Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019;51(11):2375-90.
-
27. Zimmerman A, Planek MIC, Chu C, Oyenusi O, Paner A, Reding K, et al. Exercise, cancer and cardiovascular disease: what should clinicians advise? Cardiovasc Endocr Me. 2021;10(2):62-71.
Investigation of Chronotropic Response and Exercise Intolerance in Colorectal Cancer Survivors
Year 2026,
Volume: 4 Issue: 1, 14 - 21, 23.01.2026
Mehmet Fatih Sanver
,
Melda Saglam
,
Ebru Çalık
,
Saadettin Kılıçkap
,
Naciye Vardar Yaglı
Abstract
Purpose: Advances in colorectal cancer (CRC) treatment have significantly increased patient survival rates. However, cancer-specific therapies can induce chronic adverse effects on the cardiovascular system, leading to various symptoms in survivors. The aim of this study was to investigate exercise capacity and cardiac responses to exercise in CRC survivors and compare them with healthy individuals.
Methods: The study included twenty-three CRC survivors (aged 18–65 years) and twenty-two age and sex-matched healthy individuals. All participants underwent a Cardiopulmonary Exercise Test (CPET). Physical activity level (SF-IPAQ) and fatigue severity (BFI) were assessed. The chronotropic index (CI) was calculated using the formula (HRpeak-HRrest)/(220-age)-(HRrest).
Results: Maximal oxygen consumption and the difference between resting heart rate and the peak heart (ΔHR) rate achieved during exercise were lower in CRC survivors compared to healthy individuals (p<0.001, p=0.04, respectively). CI was observed insufficient in 11 (47.83%) CRC survivors and 3 (13.64%) healthy individuals (p=0.01). Whereas physical activity level was similar between the groups (p=0.10), fatigue was more common in CRC survivors (p<0.001).
Discussion: Significant reduction in VO2peak, the objective measure of exercise capacity, and the statistically higher prevalence of CI (CI<80%) in CRC survivors highlight a compromise in the cardiovascular system's functional reserve. We suggest that CI acts as a sensitive functional marker of subclinical cardiotoxicity induced by cancer treatments, pointing to an impaired cardiac autonomic response, rather than solely structural heart damage. These findings underscore the long-term need for routine screening of cardiac functional response in this growing population of survivors.
References
-
1. Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin. 2023;73(3):233-54.
-
2. Islami F, Goding Sauer A, Miller KD, Siegel RL, Fedewa SA, Jacobs EJ, et al. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J Clin. 2018;68(1):31-54.
-
3. Toohey K, Pumpa KL, Arnolda L, Cooke J, Yip D, Craft PS, et al. A pilot study examining the effects of low-volume high-intensity interval training and continuous low to moderate intensity training on quality of life, functional capacity and cardiovascular risk factors in cancer survivors. PeerJ. 2016;4:e2613.
-
4. De Couck M, Gidron Y. Norms of vagal nerve activity, indexed by Heart Rate Variability, in cancer patients. Cancer Epidemiol. 2013;37(5):737-41.
-
5. Koelwyn GJ, Jones LW, Moslehi J. Unravelling the causes of reduced peak oxygen consumption in patients with cancer: complex, timely, and necessary. J Am Coll Cardiol. 2014;64(13):1320-2.
-
6. Bonsignore A, Marwick TH, Adams SC, Thampinathan B, Somerset E, Amir E, et al. Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy. JACC CardioOncol. 2021;3(5):678-91.
-
7. Yoon SY, Oh J. Cardiovascular Autonomic Dysfunction Before and After Chemotherapy in Cancer Patients. J Clin Neurol. 2024;20(6):551-62.
-
8. Lakoski SG, Jones LW, Krone RJ, Stein PK, Scott JM. Autonomic dysfunction in early breast cancer: Incidence, clinical importance, and underlying mechanisms. Am Heart J. 2015;170(2):231-41.
-
9. Bertrand E, Caru M, Lemay V, Andelfinger G, Laverdiere C, Krajinovic M, et al. Heart rate response and chronotropic incompetence during cardiopulmonary exercise testing in childhood acute lymphoblastic leukemia survivors. Pediatr Hematol Oncol. 2021;38(6):564-80.
-
10. Paolillo S, Agostoni P, De Martino F, Ferrazzano F, Marsico F, Gargiulo P, et al. Heart rate during exercise: mechanisms, behavior, and therapeutic and prognostic implications in heart failure patients with reduced ejection fraction. Heart Fail Rev. 2018;23(4):537-45.
-
11. Groarke JD, Tanguturi VK, Hainer J, Klein J, Moslehi JJ, Ng A, et al. Abnormal exercise response in long-term survivors of hodgkin lymphoma treated with thoracic irradiation: evidence of cardiac autonomic dysfunction and impact on outcomes. J Am Coll Cardiol. 2015;65(6):573-83.
-
12. Arab C, Dias DP, Barbosa RT, Carvalho TD, Valenti VE, Crocetta TB, et al. Heart rate variability measure in breast cancer patients and survivors: A systematic review. Psychoneuroendocrinology. 2016;68:57-68.
-
13. Ness KK, Plana JC, Joshi VM, Luepker RV, Durand JB, Green DM, et al. Exercise Intolerance, Mortality, and Organ System Impairment in Adult Survivors of Childhood Cancer. J Clin Oncol. 2020;38(1):29-42.
-
14. Vigo C, Gatzemeier W, Sala R, Malacarne M, Santoro A, Pagani M, et al. Evidence of altered autonomic cardiac regulation in breast cancer survivors. J Cancer Surviv. 2015;9(4):699-706.
-
15. Saglam M, Arikan H, Savci S, Inal-Ince D, Bosnak-Guclu M, Karabulut E, et al. International physical activity questionnaire: reliability and validity of the Turkish version. Percept Mot Skills. 2010;111(1):278-84.
-
16. Azak A, Çınar S. Lenfomalı (hodgkin ve non-hodgkin) hastalarda yorgunluk sendromu ve etkileyen faktörler. Turk J Hematol Oncol. 2005;15:78-83.
-
17. American Thoracic S, American College of Chest P. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003;167(2):211-77.
-
18. Cole CR, Foody JM, Blackstone EH, Lauer MS. Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort. Ann Intern med. 2000;132(7):552-5.
-
19. Lauer MS, Francis GS, Okin PM, Pashkow FJ, Snader CE, Marwick TH. Impaired chronotropic response to exercise stress testing as a predictor of mortality. JAMA. 1999;281(6):524-9.
-
20. Cramer L, Hildebrandt B, Kung T, Wichmann K, Springer J, Doehner W, et al. Cardiovascular function and predictors of exercise capacity in patients with colorectal cancer. J Am Coll Cardiol. 2014;64(13):1310-9.
-
21. Viale PH, Yamamoto DS. Cardiovascular toxicity associated with cancer treatment. Clin J Oncol Nurs. 2008;12(4):627-38.
-
22. Grote S, Ricci JM, Dehom S, Modeste N, Sealy DA, Tarleton HP. Heart Rate Variability and Cardiovascular Adaptations Among Cancer-Survivors Following a 26-Week Exercise Intervention. Integr Cancer Ther. 2020;19.
-
23. Schmid D, Leitzmann MF. Cardiorespiratory fitness as predictor of cancer mortality: a systematic review and meta-analysis. Ann Oncol. 2015;26(2):272-8.
-
24. Wagner LI, Cella D. Fatigue and cancer: causes, prevalence and treatment approaches. Br J Cancer. 2004;91(5):822-8.
-
25. Velthuis MJ, May AM, Koppejan-Rensenbrink RA, Gijsen BC, van Breda E, de Wit GA, et al. Physical Activity during Cancer Treatment (PACT) Study: design of a randomised clinical trial. BMC Cancer. 2010;10:272.
-
26. Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, et al. Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019;51(11):2375-90.
-
27. Zimmerman A, Planek MIC, Chu C, Oyenusi O, Paner A, Reding K, et al. Exercise, cancer and cardiovascular disease: what should clinicians advise? Cardiovasc Endocr Me. 2021;10(2):62-71.