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Fatigue: a Complex Symptom and Its Impact on Cancer and Heart Failure Jacqueline Aparecida Borges, Mônica Maria Pena Quintão, Sergio S

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Fatigue: a Complex Symptom and Its Impact on Cancer and Heart Failure Jacqueline Aparecida Borges, Mônica Maria Pena Quintão, Sergio S International Journal of Cardiovascular Sciences. 2018;31(4)433-442 433 REVIEW ARTICLE Fatigue: A Complex Symptom and its Impact on Cancer and Heart Failure Jacqueline Aparecida Borges, Mônica Maria Pena Quintão, Sergio S. M.C. Chermont, Hugo Tannus Furtado de Mendonça Filho, Evandro Tinoco Mesquita Universidade Federal Fluminense (UFF), Niterói, RJ - Brazil Abstract nervous system) or peripheral (muscular skeletal) origin, both of which may be present in patients with cancer. In chronic diseases like cancer and heart failure (HF), The present review aims to discuss the new concepts in fatigue is a common and complex symptom from an the assessment of fatigue in oncological patients. These etiological and pathophysiological point of view, thus, concepts are fundamental to professionals who work in a relevant issue in the recent area of oncocardiology. the emerging area of oncocardiology. Fatigue is prevalent in 80-90% of the oncological patients treated with chemotherapy and/or radiotherapy and Introduction affects approximately 50-96% of the individuals with IC. The toxicity attributed to chemotherapeutic agents can The survival rate of patients with cancer has improved determine the patients’ degree of fatigue and may even substantially in recent decades with the emergence predict their survival. In recent decades, the advancement of new chemotherapeutic agents and advancement of antineoplastic therapies has substantially impacted of radiotherapy. However, oncological patients are the survival of patients with cancer, and the risks of more susceptible to cardiotoxic effects developed harmful effects from these therapies to the cardiovascular during treatment, which can increase the morbidity system have been increasingly described. Therefore, the and mortality of this population.1 Within this new cooperation between oncologists and cardiologists has scenario, oncocardiology emerged as a new area of led to the emergence of oncocardiology and the new specialization based on a multidisciplinary integrative concept of cardiac surveillance. Cardiotoxicity is one approach. Oncocardiology seeks to improve the quality of the clinical complications in the treatment of cancer, of cardiologic care offered to patients with cancer, and to and its typical manifestation is left ventricular systolic study the different dimensions of cardiotoxicity. dysfunction. New diagnostic and therapeutic strategies Among cardiovascular symptoms, fatigue is a have been employed in the cardiac surveillance of common and very prevalent clinical manifestation patients with cancer. Fatigue in these patients has been in patients with cancer, and its characterization and carefully studied with a multidisciplinary approach mechanisms still defy healthcare professionals. Fatigue and with the development of visual scales to quantify associated with cancer is a subjective experience and correlate better its real impact on these individuals’ characterized by fatigue not relieved by sleep or rest, quality of life and survival. The Fatigue Pictogram and and is considered a predictor of decreased personal Piper Fatigue Scale are tools increasingly used in research satisfaction and quality of life.2 The symptom fatigue and clinical practice. The mechanisms involved in fatigue, varies in duration and intensity, reduces in varying from a conceptual point of view, may be of central (central degrees the patient’s ability to develop daily activities, and decreases the functional capacity of patients with cancer.3 Fatigue can affect 80-99% of the patients with Keywords cancer treated with chemotherapy and/or radiotherapy4 Heart Failure / physiopathology; Neoplasms / and may persist for months to years. Cella et al.5 reported physiopathology; Cardiotoxicity / complications; that one-third of the patients cured of cancer showed Ventricular Dysfunction, Left; Neoplasias / drug therapy. fatigue for 5 years after the end of chemotherapy. Mailing Address: Jacqueline Aparecida Borges Rua Martins Ferreira, 81/704. Postal Code: 22271-010, Botafogo, Rio de Janeiro, RJ - Brazil. E-mail: [email protected]; [email protected] DOI: 10.5935/2359-4802.20180027 Manuscript received April 11, 2017, revised manuscript December 12, 2017, accepted December 19, 2017. Int J Cardiovasc Sci. 2018;31(4)433-442 Borges et al. Review Article Oncocardiology and the symptom fatigue 434 The multifactorial nature of fatigue associated large number of synonyms associated with this term. with cancer is a crucial point to be considered by Healthcare professionals attribute different terms to professionals dealing with oncological patients. The fatigue, such as asthenia, lethargy, exhaustion, feeling main causes of fatigue are associated with the cancer of weakness, extreme tiredness, and lack of motivation. effects and treatment on the central nervous system. Patients with cancer refer to fatigue using different Other causes include depression and anxiety, anemia, terms, such as weakness, exhaustion, fatigue, depletion, endocrine abnormalities (such as hypothyroidism and slowness, or weight.11 diabetes), activation of the immune system, inflammatory The scientific literature, in turn, defines fatigue as “a mediators, emotional stress, electrolytic disorders, subjective feeling of physical tiredness or exhaustion myopathies, pulmonary fibrosis, and heart failure (HF).6 disproportionate to the level of activity.” Additionally, HF is a complex and multisystemic syndrome found in “fatigue may manifest as difficulty or inability in elderly patients presenting with the clinical triad fatigue, initiating an activity (perception of general weakness); dyspnea, and edema. The mechanisms associated with reduced capacity of maintaining an activity (easy fatigue in HF are triggered by inadequate blood perfusion tiredness); and difficult concentration, memory problems, affecting the respiratory and peripheral muscles, leading and emotional stability (mental fatigue).”12 to decreased oxidative capacity.7,8 Fatigue affects 50-96% Muscle fatigue, in turn, is regarded by many authors of the patients with HF and is associated with a reduction as “an inability to maintain a level of potency or strength in quality of life, restriction of physical activity, and during repeated muscle contractions,”13 “decreased worse prognosis.8 strength in sustained maximal contraction,”14 and A successful HF treatment depends on a comprehensive “reduced availability of energy substrate for the skeletal assessment of the symptoms and knowledge of the muscle during exercise.”15 available approaches to alleviating not only the physical aspects of the patient but also his emotional and Mechanisms of fatigue spiritual suffering. The “person-centered care” strategy, Fatigue originates in the cerebral cortex and may including a partnership between healthcare professionals extend up to the cross-bridges of the muscle, induced and patients with HF, decreases the duration of by a reduction in the number of functional motor units hospitalization.9 The prescriptions are specific to those involved in the activity or in the frequency of triggering. patients with HF who present with dyspnea at the end of The mechanisms responsible for fatigue may be central life, with the objective of symptom relief, in addition to or peripheral and are investigated through kinesthetic full support of the team specialized in palliative care.10,11 sensations (effort and strength) and by electromyography.15 In clinical practice, healthcare professionals dedicated Electromyographic signs allow the identification of to oncology and cardiovascular diseases encounter the manifestation of fatigue of a given muscle through patients, especially elderly ones, presenting with both a reduction in the amplitude of the electrical impulse conditions. Therefore, the identification and evaluation registered, indicative of loss of recruitment or synergic of fatigue by these professionals is fundamental and must activation of multiple muscles. Another method of include scientifically validated instruments, as well as a study of the physiology of fatigue is the addition of a clinical assessment and complementary tests to perform force by supramaximal electrical stimulation during a an adequate therapeutic plan. maximal voluntary contraction, which translates into The objective of this review is to discuss the new impaired muscle activation (at a level proximal to the aspects of fatigue present in oncological patients and neuromuscular junction).16 emphasize the importance of early detection of HF and The central mechanism of fatigue occurs due to monitoring of cardiac function for more appropriate changes in the neural input arriving at the muscles, management of patients undergoing chemotherapy i.e., the recruitment of motor units remains below the and radiotherapy. ideal one for generation of adequate muscle strength during exercise.16 Defining fatigue in clinical practice Peripheral fatigue stems from homeostatic changes in There is no consensus in regards to the concept of the skeletal muscle itself and from decreased contractile fatigue. Describing fatigue is a difficult task due to a force. One of the mechanisms inducing muscle fatigue Borges et al. Int J Cardiovasc Sci. 2018;31(4)433-442 435 Oncocardiology and the symptom fatigue Review Article during exercises influencing the production of force Fatigue in heart failure is the depletion of energy substrate required for ATP Fatigue and dyspnea are cardinal symptoms of HF. synthesis and the variation in intracellular concentration
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