Atrial Fibrillation Begets Heart Failure and Vice Versa: Temporal Associations and Differences in Preserved vs. Reduced Ejection Fraction

Santhanakrishnan R; Wang N; Larson MGet al.,
Circulation. 2016 Jan 8. pii: CIRCULATIONAHA.115.018614. [Epub ahead of print]

Background

Heart failure (HF) and atrial fibrillation (AF) share predisposing factors and are closely intertwined. They each predispose the other, and when both are present prognosis worsens [1-4].
Differences in atrial remodelling and prognosis associated with AF among HF subtypes have been described. For instance, greater eccentric left atrial (LA) remodelling is seen in HF with reduced ejection fraction (HFrEF), while increased LA stiffness has been described for HF with preserved EF (HFpEF) predisposing to AF [5]. Moreover, CV outcomes after AF may be influenced by HF subtype [6].
The authors therefore hypothesise that the temporal association between AF and HF subtypes would be distinct. They aimed to investigate the association of AF with HFpEF and HFrEF in a large, community-based cohort, to obtain more information about the onset of one condition compared with the other, as opposed to previous hospital-based cohort studies. AF and HF events were ascertained longitudinally. This study is part of the Framingham Heart Study [7]. Because of echocardiography to determine HF subtype becoming widely available after 1980, participants with new-onset AF (n=1737) and/or HF (n=1166, 41% HFpEF, 44% HFrEF, 15% not classified) between 1980 and 2012 were included.

Main results

• Among subjects with HF, 38% had no AF at baseline or during follow-up, 32% had prevalent AF, 18% received an AF diagnosis within 30 days of their incident HF diagnosis, and 12% developed incident AF after their incident HF diagnosis.
• Subjects with HFpEF were more likely to have AF at any time than those with HFrEF (62% vs. 55%, P=0.02). The burden of prevalent AF was larger in the HFpEF group than HFrEF group (32% vs. 23%, P=0.002).
• The age- and sex-standardised incidence rate of AF was much higher in those with prevalent HF as compared with those without HF (47.8 vs. 7.9 per 1000 PY).
  In age- and sex-adjusted Cox-analyses, an increased risk of incident AF was observed with both prevalent HF (HR: 3.42, 95%CI: 2.10-5.56, P<0.0001) and interim HF (HR: 2.41, 95%CI: 1.89-3.08, P<0.0001). After multivariable adjustment about two-fold increased risks were seen.
• Standardised incidence rate of HF was also much higher in those with vs. without prevalent AF (31.4 vs. 4.8 per 1000 PY), and the same was true for both subtypes.
  Prevalent AF predicted incident HFpEF (HR: 2.34, 95%CDI: 1.48-3.70, P=0.0003) but not HFrEF (HR: 1.32, 95%CI: 0.83-2.10, P=0.23).
  Conversely, interim AF predicted incident HFrEF (HR: 1.71, 95%CI: 1.19-2.45, P=0.003), but not HFpEF in multivariable-adjusted analyses.
• Mortality after HF was similar in subjects with or without prevalent AF. Interim AF was, however, associated with mortality in individuals with new HFpEF (multivariable-adjusted HR: 1.58, 95%CI: 1.08-2.30, P=0.02) or new HFrEF (HR: 2.02, 95%CI: 1.46-2.79, P<0.0001).
• Mortality after AF was higher in those with HFrEF vs. HFpEF, and with an even larger difference seen with those without HF.

Conclusion

These data demonstrate the close and complex association between AF and HF. At least one third of individuals with AF develop HF at some point, and in more than half of HF subjects AF occurs. While AF can both precede and follow both types of HF, AF is more likely to be the first diagnosis. Specifically, incident HFpEF more often occurs than HFrEF when AF is already prevalent. Together, AF and HF confer poor prognosis, with risk being highest in subjects with HFrEF.

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References

1. Ho KK, Anderson KM, Kannel WB et al. Survival after the onset of
congestive heart failure in Framingham Heart Study subjects. Circulation. 1993;88:107-115.
2. McManus DD, Hsu G, Sung SH, et al. Atrial fibrillation and outcomes in heart failure with preserved versus reduced left ventricular ejection fraction. J Am Heart Assoc. 2013;2:e005694.
3. Dries DL, Exner DV, Gersh BJ, et al. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction. J Am Coll Cardiol. 1998;32:695-703.
4. Wang TJ, Larson MG, Levy D, et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation. 2003;107:2920-2925.
5. Melenovsky V, Hwang S, Redfield MM, et al. Left atrial remodelling and function in advanced heart failure with preserved or reduced ejection fraction. Circ Heart Fail. 2015;8:295-303.
6. Olsson LG, Ducharme A, Granger CB, et al. Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program. J Am Coll Cardiol. 2006;47:1997-2004
7. Kannel WB, Feinleib M, McNamara PM, et al. An investigation of coronary heart disease in families The Framingham offspring study. Am J Epidemiol. 1979;110:281-290