Subclinical HFpEF Common in Patients Undergoing AF Ablation

Subclinical heart failure with preserved ejection fraction (HFpEF) was found in about three out of every four patients undergoing catheter ablation for symptomatic atrial fibrillation (AF) in a single-center Australian study, which could have implications for how these patients are managed moving forward.

Despite the lack of overt signs of heart failure, subclinical HFpEF was associated with indicators of more-advanced left atrial (LA) cardiomyopathy, a reduced cardiopulmonary reserve, and a greater burden of AF symptoms, researchers led by Jonathan Ariyaratnam, MBBChir (University of Adelaide and Royal Adelaide Hospital, Australia), report in a study published online this week in JACC: Heart Failure.

It remains to be seen whether these patients would benefit from early use of HFpEF therapies, but identifying subclinical HFpEF does present an opportunity, according to Adrian Elliott, PhD, one of the senior authors along with Prashanthan Sanders, MBBS, PhD (both from the University of Adelaide and Royal Adelaide Hospital).

“At this stage, what we can say is that in these symptomatic patients, you can get this testing done relatively easily during a procedure, and then once you identify some of these features, it really accentuates the need to manage things like risk factors—for example, obesity and hypertension—really strictly to try and not only manage the atrial fibrillation . . . but also then to try and prevent the further progression of heart failure that might then lead downstream to heart failure events,” Elliott said. “So we think it’s an opportunity for us to really get on top of that and act early before we get into full clinical HFpEF.”

Commenting for TCTMD, Jonathan Piccini, MD (Duke University, Durham, NC), said the findings are consistent with others in showing that a significant proportion of patients with symptomatic AF have evidence of HFpEF. And that’s important because it underscores that AF and heart failure are inextricably linked and it might help explain some of the benefits of AF ablation observed in clinical trials, including those performed in patients with HFpEF, Piccini said.

He agreed that “this may be a really important opportunity to try and treat these patients early, and it’s a hypothesis, we don’t know if this is the case, but maybe if you start treating HFpEF early, you could potentially prevent the patient from advancing to a more-advanced stage of heart failure.”

Overlap Between AF and HFpEF

There’s a known overlap between AF and HFpEF when it comes to symptoms and background risk factors, Elliott said. And when patients with symptomatic AF are treated with rhythm control—ablation, for example—some of those symptoms will persist, indicating that there’s something else besides the arrhythmia affecting the clinical status.

In their prior studies of risk factor modification—ie, weight loss and exercise—in patients with AF, the investigators noticed that the participants had similar characteristics to patients with HFpEF when looking at imaging parameters, symptoms, and exercise performance, and also that the main predictors of exercise tolerance were features often observed in patients with HFpEF.

We think it’s an opportunity for us to really . . . act early before we get into full clinical HFpEF. Adrian Elliott

The current study is the next step in exploring the overlap between symptomatic AF and HFpEF, with the researchers performing noninvasive assessments in the weeks leading up to catheter ablation and invasive hemodynamic assessments at the time of the procedure.

The study included 120 patients with symptomatic AF. The presence of subclinical HFpEF was determined with invasive assessment of LA pressure at the time of the ablation procedure. HFpEF was defined as an LA pressure > 15 mm Hg, and early HFpEF was defined as an LA pressure > 15 mm Hg in response to a 500-mL saline challenge. Overall, 47.5% of patients had HFpEF, 25.8% had early HFpEF, and 26.7% had no HFpEF.

The patients with subclinical HFpEF meet criteria from the American College of Cardiology and the American Heart Association for stage B pre-HF, the authors note. “This cohort, therefore, represents a population of patients at increased risk of progression to more advanced stages of HF.”

There were no differences across the three groups in age, sex, type or duration of AF, or history of AF ablation. Compared with patients without HFpEF, however, those with HFpEF had a higher body mass index and higher CHA₂DS₂-VASc scores and were more likely to have hypertension and to be treated with ACE inhibitors/ARBs.

On resting echocardiography performed before ablation, both HFpEF and early HFpEF were associated with reductions in LA reservoir strain and LA emptying fraction. And on exercise echo, both groups had lower LA emptying fraction at peak exercise. HFpEF, but not early HFpEF, was additionally associated with decreased LV strain during exercise.

Invasive hemodynamic assessments prior to ablation showed lower LA compliance in patients with subclinical HFpEF. Electroanatomical mapping demonstrated electrical remodeling of the left atrium in the patients with subclinical HFpEF.

These differences appear to have a functional impact. On cardiopulmonary exercise testing, patients with subclinical HFpEF had a reduction in peak oxygen consumption, a lower maximum heart rate at peak exercise, and a reduced chronotropic response. Moreover, they had worse scores on the AF Symptom Severity questionnaire, although there were no differences across groups in HF symptoms.

Implications for Management

Elliott said that his team had expected many patients to have HFpEF but added that the proportion observed here—roughly three-quarters—was “a lot higher than we anticipated.”

Still, he said, “it does sort of speak to the need to really evaluate patients a little bit more thoroughly for consideration of HFpEF or even early HFpEF because at that stage what we’re thinking is that they’re probably more amenable to treatment, particularly with managing risk factors and getting on top of those risk factors early rather than later when their heart failure symptoms and hospitalizations begin.”

The invasive evaluation for HFpEF performed in this study can be done easily across centers, Elliott said, noting that there were no complications associated with the protocol and it didn’t add much time. “We think that this would be a pretty simple add-on to any AF ablation procedure.”

At this point, if a patient undergoing ablation does have HFpEF, the strategy should entail “aggressive lifestyle intervention,” Elliott said. The latest trials of medications in HFpEF have generally involved patients with clinical heart failure and recent hospitalizations, a different type of population than the one studied here, he noted.

“We don’t have the data to say that once we identify these patients we should put them straight into HFpEF drug therapy, but that’s probably the next step we need to move towards—to identify whether if we initiate those therapies,” said Elliot. “Then maybe what we end up with later is better outcomes not only from an AF perspective but from a heart failure perspective as well.”

For Piccini, “when we see an elevated left atrial pressure in the EP lab, we really should investigate it further. We probably should get a natriuretic peptide level. We might want to consider further diagnostic testing to try and definitively make the diagnosis of heart failure with preserved ejection fraction.

“Whether treating these patients who have ‘preclinical or sublclinical’ HFpEF with therapies that have been shown to work in clinical trials in persons with symptomatic HFpEF, that remains to be seen,” he continued.