Autonomic Dysfunction in Cancer
Definition
Autonomic dysfunction (AD) in cancer patients and survivors refers to dysregulation of the parasympathetic and sympathetic nervous systems resulting in abnormal cardiovascular reflexes, impaired heart rate variability, orthostatic hypotension, and in some cases inappropriate sinus tachycardia or POTS. It is more prevalent in cancer patients and survivors than in healthy controls.
Key Concepts
Epidemiology and Manifestations
- AD is more prevalent in cancer patients and survivors than healthy controls; most frequently identified in patients with haematological malignancies. (sources/arrhythmia-cardio-oncology-aha-2021, rating: very high)
- Manifestations include:
- Decreased parasympathetic activity: increased resting heart rate; decreased heart rate variability (HRV); abnormal heart rate recovery ≤1 minute after exercise.
- Decreased sympathetic activity: abnormal blood pressure responses; orthostatic hypotension; syncope.
- Specific syndromes: inappropriate sinus tachycardia (IST); postural orthostatic tachycardia syndrome (POTS). (sources/arrhythmia-cardio-oncology-aha-2021)
Aetiology — Cancer and Therapy-Related Contributors
- Direct therapy contributions: anthracyclines, taxanes, vinca alkaloids, platinum-based agents, head and neck irradiation, and haematopoietic stem cell transplantation (HSCT) have all been associated with AD. (sources/arrhythmia-cardio-oncology-aha-2021)
- Other contributors: psychological stress, sleep disturbances, weight gain, and loss of cardiometabolic fitness during cancer treatment. (sources/arrhythmia-cardio-oncology-aha-2021)
- In a rat model of doxorubicin cardiotoxicity, decreased HRV preceded the development of cardiomyopathy — AD may be an early marker preceding structural cardiac dysfunction. (sources/arrhythmia-cardio-oncology-aha-2021)
- Fullerenol and dexrazoxane (cardioprotective agents) have been shown to attenuate anthracycline-induced AD in animal models. (sources/arrhythmia-cardio-oncology-aha-2021)
Clinical Impact and Outcomes
- Hodgkin lymphoma survivors treated with mediastinal radiation: abnormal heart rate recovery was associated with decreased exercise duration and increased mortality. (sources/arrhythmia-cardio-oncology-aha-2021)
- Bone marrow transplantation survivors: decreased HRV associated with fatigue, decreased functional capacity, and increased mortality. (sources/arrhythmia-cardio-oncology-aha-2021)
- Breast cancer patients: AD associated with increased fatigue and decreased exercise capacity. (sources/arrhythmia-cardio-oncology-aha-2021)
- Postulated mechanism: AD promotes inflammation and endothelial dysfunction → contributes to long-term cardiovascular disease in cancer survivors. (sources/arrhythmia-cardio-oncology-aha-2021)
Treatment
Non-Pharmacological
- Structured aerobic exercise training during or after cancer therapy has been shown to reverse AD in patients with breast cancer and in testicular cancer survivors. (sources/arrhythmia-cardio-oncology-aha-2021)
- General measures for orthostatic hypotension: increased salt and fluid intake; leg elevation and compression stockings; avoidance of vasodilatory medications. (sources/arrhythmia-cardio-oncology-aha-2021)
- A team-based approach (exercise therapists, psychologists, nurses) is essential for improving outcomes — consistent with AHA cardio-oncology rehabilitation framework. (sources/arrhythmia-cardio-oncology-aha-2021)
Pharmacological
- Orthostatic hypotension: midodrine; fludrocortisone; pyridostigmine; droxidopa. (sources/arrhythmia-cardio-oncology-aha-2021)
- Inappropriate sinus tachycardia: Ivabradine is an attractive option (If channel inhibitor; heart rate-specific; minimal vasodilatory effects) — data are lacking and systematic evaluation is needed. (sources/arrhythmia-cardio-oncology-aha-2021)
Contradictions / Open Questions
- Most evidence for AD in cancer is from small observational studies; no RCTs have tested interventions specifically targeting cancer-related AD. (sources/arrhythmia-cardio-oncology-aha-2021)
- Whether dexrazoxane's attenuation of AD in animal models translates to reduced AD incidence or improved outcomes in clinical settings is not established. (sources/arrhythmia-cardio-oncology-aha-2021)
- Ivabradine for IST in cancer lacks systematic evaluation; its use is currently empirical. (sources/arrhythmia-cardio-oncology-aha-2021)
Connections
- Related to concepts/Cardio-Oncology
- Related to concepts/Cancer-Associated-Arrhythmia
- Related to concepts/Cancer-Therapy-Related-CV-Toxicity
- Related to concepts/Cardiac-Rehabilitation
- Related to sources/arrhythmia-cardio-oncology-aha-2021