New evidence that women with breast cancer face an increased risk for atrial fibrillation (AF) comes from a multiethnic study of more than 85,000 older American women.
The incidence of new-onset AF was 0.6%, 2.1%, and 3.3% at 30 days, 6 months, and 1 year after a breast cancer diagnosis, compared with 0.2%, 0.9%, and 1.8%, respectively, among matched healthy women without breast cancer.
The rate of a new AF was highest in the first 60 days after a cancer diagnosis, increasing 0.6% every 30 days, and 0.3% every 30 days thereafter across 1-year of follow-up.
The increased incidence of AF was associated with higher cardiovascular mortality but not cancer-related mortality, lead author Avirup Guha, MD, Case Western Reserve University, Cleveland, reported at the virtual American Heart Association Scientific Sessions 2021.
AF is the most typical arrhythmia noted in cancer patients, with an incidence that varied from 1.3% to 4.6% in previous Canadian and Danish breast cancer cohorts, he noted.
To examine the burden in the United States, Guha and colleagues used the Surveillance, Epidemiology, and End Results-Medicare database to identify 85,423 women at least 66 years old at the time of their breast cancer diagnosis, between 2007 and 2014, and propensity matched them 1:1 to Medicare beneficiaries without cancer.
In all, 2993 women developed new-onset AF after breast cancer diagnosis, 9425 had AF prior to cancer diagnosis, and 73,005 had no AF at 1-year follow-up, according to the results, also published in the European Heart Journal.
New-onset AF was more common in older women, those with cardiovascular risk factors, such as hypertension, diabetes, and previous stroke, and among Black women. The age-standardized AF incidence was 49.9 per 1000 person-years in White women vs 58.8 per 1000 person-years in Black women in 2014.
“This finding is contrary to what is known from the general population, where the incidence of AF is known to be higher in Whites compared to Black females,” the authors write. “Although not wholly explained by our data, Black females have a higher likelihood of ER/PR- and later stage of a breast cancer diagnosis, which may be contributing factors.”
Women who did not receive surgery (23.5% vs 10.4%; P < .001) or radiation (66.5% vs 52.3%; P < .001) as first-line treatment had a higher risk of developing AF, as did those with advanced- vs early-stage disease at diagnosis (stage IV, 14.8% vs stage I, 6.3%; P < .001).
After traditional risk factors were controlled for, cancer stage stood out as a significant risk factor for AF, with adjusted hazard ratios (aHRs) of 1.51, 2.53, and 4.21 for stages II, III, IV, respectively, compared with stage I disease, Guha said.
Remarkably, left-sided breast cancer and breast cancer subtype based on receptor status (HER2Neu/HR) were not associated with AF risk, the authors note.
The risk for AF was lower in women treated initially with implanted radiation, also known as brachytherapy, than with beam radiation (aHR, 0.51; 95% CI, 0.37 – 0.70). This is a novel finding and possibly due to a lower cardiac dose from radiation implants in the breast, the authors note.
Women who underwent more complex surgery, like modified radical mastectomy, compared with a simpler one, like lumpectomy, had a higher AF incidence (aHR, 1.55; 95% CI, 1.31 – 1.85). Blood loss or electrolyte imbalance associated with longer surgery and the impact of cardiac fibrosis in late-stage cancer may explain the finding, the authors suggest.
Notably, use of cardiac medications — beta-blockers, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and spironolactone/eplerenone — was associated with lower risk for AF in women with breast cancer across all grades (joint test P value > .05 for all three drug classes).
Increased Mortality
All-cause death was higher in women with new-onset AF after cancer diagnosis. At 1 year, 62.2% of women who developed AF in the first 30 days were alive, compared with approximately 85.0% of women who had AF prior to their cancer diagnosis. “This [increased risk] is related to cardiovascular mortality but not to breast cancer-specific mortality,” Guha said.
Cardiovascular mortality was threefold higher in women with incident AF in the first 30 days (aHR, 3.00; 95% CI, 1.28 – 7.00), but not in those with AF prior to their cancer diagnosis (aHR, 1.36; 95% CI, 1.00 – 1.84).
The cause of cardiovascular death in patients with incident AF was heart failure (63.3%), systemic embolism (16.7%), ischemic stroke (16.7%), and arrhythmic (13.3%).
In an exploratory analysis, anticoagulant use was associated with lower all-cause mortality in women with incident AF (aHR, 0.43; 95% CI; 0.21 – 0.89).
“The present study supports the use of anticoagulants in breast cancer since AF was more associated with cardiovascular mortality than with cancer mortality,” Jose L. Merino, MD, PhD, La Paz University Hospital, Universidad Autónoma de Madrid, says in an accompanying editorial.
“This has important implications for the clinician who should be reassured to follow the general recommendations for AF thromboembolic prevention in this population,” he said. “The latter is particularly relevant because nowadays breast cancer patients with AF often do not receive anticoagulation despite having the indication for it.”
Merino noted that the overall results are not generalizable to all cancer patients, given the older age of the cohort, but joined Guha in calling for integrated management with cardio-oncology specialists and protocols, like the EHRA-PATHS project, to care for patients with breast cancer.
Commenting for theheart.org | Medscape Cardiology, Deepak Bhatt, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center, Boston, said this is “a very interesting analysis that highlights an overlooked association: a higher risk of atrial fibrillation in women after they are diagnosed with breast cancer.”
Some of this excess risk was driven by conventional cardiac risk factors, but breast cancer stage also appeared to increase the risk, he added. “This latter finding may be due to cancer elevating cardiovascular risk in ways we are only now beginning to study and appreciate.”
“Intriguing associations, as in this study, are part of the reason that cardio-oncology is growing so rapidly,” Bhatt observed. “I suspect future research will find many interconnected pathways of thrombosis and inflammation that drive not only cardiovascular, but also cancer risk.”
The study was supported in part by National Institutes of Health grants and by the American Heart Association-Robert Wood Johnson Foundation Harold Amos grant. Guha is supported by an American Heart Association-Strategically Focused Research Network Grant in Disparities in Cardio-Oncology. Merino reports grants and personal fees from Abbott, Boston Scientific, Medtronic, Microport, and Sanofi.
Eur Heart J. Published November 14, 2021. Full text, Editorial
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