Arrhythmia prevention and management in cancer survivors


KEY POINTS

  • Cancer survivors are at risk of developing arrhythmias, often not diagnosed until clinically evident, and at times with life-threatening consequences.

  • The long-term risk of recurrent arrhythmias once in remission and after cessation of cancer therapies is unknown.

  • Arrhythmias occur with similar frequency in patients with chemotherapy-induced cardiomyopathy and other forms of left ventricular dysfunction.

  • Cardiac resynchronization demonstrates benefit in patients with chemotherapy-induced cardiomyopathy.

  • Autonomic dysfunction is frequently encountered in cancer survivors treated with chemotherapy and/or radiation.

It is well established from multiple epidemiologic studies that cardiovascular (CV) disease is more common in cancer survivors than in the general population. Although attention is frequently given to ischemic heart disease and heart failure, arrhythmias are also significantly increased in the survivorship population, with an incidence of 1.3% by age 45 based on data from the Childhood Cancer Survivors Study. Unfortunately, risk factors for the development of arrhythmias in cancer survivors are not well established, which makes the development of screening and prevention strategies more challenging.

Atrial and ventricular arrhythmias in cancer survivors

Atrial arrhythmias, particularly atrial fibrillation (AF), are well described cardiotoxicities of many different cancer therapeutics including cytotoxic and targeted therapeutics ( Table 31.1 ). However, little is known about the long-term risk of recurrent arrhythmias once the offending agent has been stopped. Thus far it is unclear if the development of arrhythmias while taking a cancer therapeutic increases the likelihood of future recurrent episodes. In patients on ibrutinib, for instance, the risk seems to reside with those who either have a history of AF or are otherwise at risk of AF. Thus, at least these patients have the substrate for AF, which then emerges with triggers related to the malignancy and/or therapy.

TABLE 31.1
Cancer Treatments Frequently Associated With Atrial Arrhythmias
DRUG CLASS FREQUENCY
Doxorubicin Anthracycline 10.3%
Melphalan Alkylating 13%
Gemcitabine Antimetabolite 8%
Carfilzomib Proteasome inhibitor 3.8%
Interleukin-2 Immunotherapy 13%
Sorafenib Tyrosine kinase inhibitor 5%
Ibrutinib Bruton’s tyrosine kinase inhibitor 14%

Such suggestive but nonconfirmed persistent risk estimates lead to significant management dilemmas, especially as it relates to anticoagulation. It is not clear if patients with an elevated stroke risk as determined by their CHA 2 DS 2 -VASc score (≥2 in men, and ≥3 in women, see Fig. 19.1 ), should receive long-term anticoagulation if the arrhythmia only occurred while taking their cancer therapeutic. Given these uncertainties, the ARCHER trial (Clinicaltrials.gov – NCT04118530) was designed to evaluate the long-term risk of recurrent atrial fibrillation in stem cell transplant survivors with elevated stroke risk who developed new-onset AF after conditioning chemotherapy. Patients who meet the inclusion criteria will have a subcutaneous implantable loop recorder inserted to monitor for recurrent arrhythmias. The data from this trial will help to inform our decisions on the long-term management of these patients.

If atrial or ventricular tachyarrhythmias are observed in cancer survivors, the evaluation and treatment of these patients should follow the same guidelines and recommendations as those for the general population. In the setting of AF, patients with an elevated CHA 2 DS 2 -VASc score should be started on anticoagulation to minimize the risk of thromboembolism, if deemed to be at a low bleeding risk ( Fig. 19.2 ). Just like for other cardiovascular diseases, management of AF anticoagulation in cancer survivors increasingly matches those without cancer further out from malignancy and therapy. Rate versus rhythm control strategies should be considered based on the presence of additional symptoms or CV abnormalities. An evaluation for cardiomyopathy and/or ischemic heart disease should be initiated if arrhythmias (especially ventricular arrhythmias) are observed in patients with long-term CV risk who have received treatments (i.e., anthracyclines, chest radiation). ,

Several studies have evaluated the arrhythmic burden in patients with chemotherapy-induced cardiomyopathy. Historically, this type of nonischemic cardiomyopathy was thought to portend a worse prognosis when compared with other etiologies. Arrhythmias were thought to be one potential reason for this observation. More recently however, a large retrospective study from the Mayo Clinic suggested similar outcomes between cancer survivors with an anthracycline-mediated cardiomyopathy, and other types of left ventricular dysfunction. Specifically, no significant difference was found in overall survival, freedom from heart transplantation, or freedom from implantable cardioverter defibrillator (ICD) therapies in the different groups. Moreover, intracardiac device evaluation revealed nonsustained ventricular tachycardia to be the most common arrhythmia in patients with anthracycline-mediated cardiomyopathy (73.9%), followed by AF (56.6%) and sustained ventricular tachycardia (VT) or ventricular fibrillation (30.4%). These values did not significantly differ between the different groups. A related study by Fradley and colleagues reported similar results. When comparing patients with chemotherapy-induced cardiomyopathy with patients with other forms of nonischemic cardiomyopathy no significant difference was seen in atrial or ventricular arrhythmias. Patients with an ischemic cardiomyopathy demonstrated higher rates and risk of both nonsustained ventricular tachycardia and the combined outcome of sustained VT or ventricular fibrillation however. It remains essential to monitor for and treat arrhythmias routinely if they are observed in these patients.

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