Atrial Fibrillation and Heart Failure: Too much talk and not enough action

Atrial fibrillation is very common in patients who are diagnosed with heart failure. Heart failure is also common in persons with AF, but it is not always recognized or diagnosed. Among patients referred for catheter ablation, 65% have heart failure with preserved ejection fraction as defined by the European Society of Cardiology.(1) Patients with HF have significantly worse quality of life when they are in AF compared with sinus rhythm.(2) Increased time in AF is strongly associated with increased hospitalization for heart failure & death. (3,4) Randomized controlled trials demonstrate that catheter ablation of AF improves left ventricular function, functional class, and cardiovascular outcomes in those with HF and reduced EF(5) and observational data suggest that ablation may improve cardiovascular outcomes in persons with AF and HFpEF.(6) As we begin to further refine our understanding of HF we now recognize that there are important phenotypic differences across persons with AF and HF, including HFrEF and HFpEF.

In this issue of JACC: Clinical Electrophysiology, Inciardi and colleagues describe outcomes in patients with AF and HF according to HF phenotype. Among 21,105 patients in the international ENGAGE AF TIMI 48 trial that compared vitamin K antagonism and edoxaban for the prevention of stroke, more than half had a history of HF. Among these 12,124 (57%) patients with AF and HF 38% had HFrEF, 40% had HFpEF (LVEF >=50%), and 22% had an unknown ejection fraction. In those with AF and prior HF, the annual rate of HF hospitalization or HF death (4.95%) was more than twice the rate of stroke or systemic embolism (1.77%). Rates of HF hospitalization & HF death were approximately 2x higher in those patients with HFrEF vs HFpEF. Notably, the study found that patients with persistent forms of AF had higher rates of HF hospitalization or HF death. In this large cohort, hospitalization for HF was not a benign endpoint, as hospitalizations for HF presaged higher mortality rates in both those with HFrEF and HFpEF.

As with any research study, there are some limitations that should be kept in mind. The LVEF and HF phenotype were unknown in a fifth of the cohort. Like many contemporary clinical trials, there was limited classification & characterization of AF type and AF density. Finally, it is important to note that there was no information on HFmrEF, a phenotype that has been increasingly recognized and distinguished in clinical practice and research studies.

The findings from the TIMI investigators reinforce and emphasize that patients with AF and HF are at high-risk for adverse outcomes. HF events are not benign events; they are associated with subsequent increased mortality. These findings have important implications for the treatment of AF with concomitant HF. HF is significant public health problem, especially in those with persistent forms of AF. HF is the most common complication of AF, significantly more common than stroke. Despite this, we understand the prevention of stroke far better than the prevention or treatment of HF among persons with AF. The strength & level of evidence of guidelines for AF ablation in HFrEF (Class IIB, Level Evidence B-R) (7) are behind the evidence base, despite the known limitations of medical therapy. For example, it is not clear that persons with HFrEF in AF derive the same benefit from beta-blocker therapy as those in sinus rhythm.(8) In contrast, there are now multiple clinical trials demonstrating improvement in cardiovascular outcomes with ablation compared with medical therapy in those with AF and HFrEF.(5)

While HFrEF is easily recognized and diagnosed following echocardiography, HFpEF is often unrecognized in those with AF. While rhythm control has been associated with improved survival in HFpEF(9), we need to clarify whether catheter ablation of AF improves cardiovascular outcomes in patients with HFpEF in large randomized trials. Furthermore, we need to better understand how to ablate in persons with HFpEF. Is pulmonary vein isolation alone optimal in a first procedure? Will extensive adjunctive ablation run the risk of greater hemodynamic complications (i.e. stiff atrial syndrome or decreased atrial systolic function) in these persons with HFpEF who have impaired diastolic function and decreased compliance? Can renal sympathetic denervation improve both blood pressure reduction and maintenance of sinus rhythm when performed alongside catheter ablation of AF? Finally, we need to better understand the magnitude of benefit of ablation in persons with HFpEF. Will the improvements mirror those we see in HFrEF or will they be different?

So where are we in 2023 with respect to AF complicated by HF? The results from Inciardi and colleagues highlight more than ever that these patients are at increased risk for adverse outcomes. We know that in many patients with HFrEF catheter ablation of AF will improve outcomes. We know that we often fail to recognize and diagnose HFpEF when it is present, and we need to maintain a high suspicion anytime we encounter a patient with AF and dyspnea. However, we don’t know the best rhythm control option in HFpEF. W don’t know if catheter ablation definitively improves outcomes in HFpEF and we need to figure that out in randomized trials as quickly as possible for the benefit of all. In the case of AF and HF, there has been a lot of talk and debate, but not enough action.