Response to Letter Regarding Article, “Atrial Fibrillation Begets Heart Failure and Vice Versa: Temporal Associations and Differences in Preserved vs. Reduced Ejection Fraction”

We appreciate the insights presented by Providencia et al in a letter referring to our manuscript “Atrial Fibrillation Begets Heart Failure and Vice Versa”.¹ We share the view that the close association of atrial fibrillation (AF) and heart failure (HF) may represent clinical manifestations of the same underlying “whole heart” cardiomyopathy, driven by common mechanisms such as fibrosis and inflammation.² The authors raise the question of whether temporality in AF and HF development may support a global cardiomyopathy.

We focused our manuscript on HF subtypes, which did not allow for examination of subgroups with concurrent versus pre-existing and/or future AF due to limited power within each HF subtype. However, the effect of concurrent AF/HF (versus diagnoses separated in time) was previously examined for overall HF among Framingham Heart Study participants.³ In subjects with AF, HF as a comorbid condition was associated with higher mortality, with similar effect sizes for prior HF (HR 2.2, 95% CI 1.6–3.0 in men) and HF diagnosed concurrently on the same day as AF (HR 2.4, 95% CI 1.6–3.5 in men). Conversely, in those with known HF, AF (whether pre-existing or concurrent) was not associated with increased mortality. Similarly, in a study from Olmsted County that examined participants with HFpEF, the presence of concurrent AF (diagnosed within 30 days of HF) showed a trend towards poor survival but was not significant in an age- and sex-adjusted model compared with sinus rhythm patients (P=0.11).⁴ This study did not directly compare mortality among participants with concurrent versus prevalent AF. Interestingly, individuals with prior AF had larger left atrial volumes compared with those with concurrent AF (55 versus 47 ml/m², respectively, P<0.05).

Taken together, these existing studies do not support a worse prognosis among individuals who develop concurrent HF and AF compared with those who develop HF and AF separated in time. However, we do know that AF and HF conjointly portend a poor prognosis. We agree with the authors that much remains to be discovered with respect to defining underlying pathophysiologic mechanisms, with the ultimate goal of targeted therapies, whether they be aimed at rhythm control or myocardial processes. We also find intriguing the concept of distinct atrial and ventricular myopathic processes as raised by Providencia et al, and agree that advanced imaging techniques may be useful in interrogating these processes in future work.