Subclinical Atrial Disease: A Window to Prevent AF and HF?

Jake Remaly

January 18, 2022

If physicians can diagnose subclinical atrial disease, early detection may provide an opportunity to prevent both atrial fibrillation and heart failure, according to a newly spelled out hypothesis by cardiologists in Europe.

For primary care doctors, the theory suggests that referring patients early on for cardiovascular assessment might help avert serious illness.

Subclinical atrial disease, which has not yet been well defined by researchers but can be identified using imaging, biomarkers, or other approaches, may be "common soil" for heart failure, atrial fibrillation, and stroke, suggest researchers in a viewpoint published last month in the European Heart Journal.

The questions and possibilities raised in the article — authored by 30 researchers with the Heart Failure Association (HFA) of the European Society of Cardiology — could have important implications for patients and prevention efforts, said Sana M. Al-Khatib, MD, MHS, with Duke University Medical Center, Durham, North Carolina.

The framework "differs somewhat from how physicians and researchers typically think about heart failure and atrial fibrillation [AF]," Al-Khatib, who was not involved in the report, told Medscape Medical News.

Dr Sana Al-Khatib

The prevailing thinking among heart specialists is that the relationship between AF and HF is causal and bi-directional: AF can cause HF, HF can cause AF, Al-Khatib said. "The framework they are proposing is that of 'parallel trajectories activated by a common underlying myopathy that affects both the atrial and the ventricular myocardium.' While this concept is not entirely novel, it is more explicitly described in this report."

The proposed paradigm makes room for an explanation about why many patients fail to respond well to current treatments for AF, a co-author of the paper, Frank Ruschitzka, MD, of the University Hospital Zurich, Switzerland, and past president of the HFA, said in an interview. "We have to better control where this atrial fibrillation originates," he said.

Al-Khatib and her colleagues previously outlined priorities for studying the "complex interrelations" between AF and HF, which they had discussed during a workshop hosted by the US National Heart, Lung, and Blood Institute in 2019.

"AF and HF are closely intertwined, with each condition predisposing to the other," they wrote in June 2020 in Circulation. Still, doctors have a "limited understanding as to whether HF after AF occurs because of shared underlying mechanisms, with a common pathobiology of AF and HF. In contrast, there may also be hemodynamic and other triggers for cardiac remodeling that are specifically driven by AF" and make progression to HF more likely.

"Paradigm Change"

The "close convergence" of HF and AF in clinical and epidemiologic studies "allows for a paradigm change," according to the European group, led by Andrew J.S. Coats, MD, PhD, DSc, with the University of Warwick in Coventry, UK, and the president of the HFA. According to their hypothesis, rather than a sequential relationship, in which one condition causes the other, the link may involve underlying atrial derangement.

In this framework, detecting subclinical atrial disease "offers a window of opportunity for interventions that could prevent deterioration to clinical disease, including AF, stroke, and HF with preserved/reduced ejection fraction and could potentially allow the reversal of subclinical disease," they write.

Stressors like aging, cardiometabolic risk factors, and genetic predisposition may trigger pathogenic mechanisms such as inflammation, endothelial and microvascular dysfunction, fibrosis, hypercoagulability, and atrial stretch. These mechanisms can then affect the atrial myocardium and lead to structural, electrical, and functional changes.

Subclinical disease may then progress to overt clinical disease that manifests as AF, HF, and thromboembolism.

Interventions for patients with subclinical disease might include exercise, dietary, and lifestyle interventions, antithrombotic therapy, or cardioprotective medications. Existing treatments or new agents could be tested in patients with subclinical atrial disease.

Dr Frank Ruschitzka

"Lowering filling pressures and attenuation of neurohumoral activation with RAAS [renin–angiotensin–aldosterone system] inhibitors" might be one treatment approach, Ruschitzka said. New drugs to treat obesity or diabetes may also play a role. "We have to show whether atrial fibrillation will be better controlled in a patient who is well treated on an SGLT2 inhibitor."

Investigators also could examine the effect of targeting risk factors like hypertension, sleep apnea, obesity, and diabetes in patients with subclinical disease, Al-Khatib said.

"What is not clear is which interventions, including medications, are most effective at preventing or slowing down atrial fibrosis and other forms of atrial remodeling that can be used even before AF manifests itself clinically," she said.

Awareness of the Entity

Methods to identify subclinical atrial disease already exist and include anatomical, functional, histological, electrical, and biochemical approaches.

"In fact, atrial disease could be diagnosed early enough with the currently available modalities," Dimitrios Farmakis, MD, PhD, of the University of Cyprus Medical School, Nicosia, Cyprus, and a co-author of the HFA document, told Medscape Medical News. "What is missing is a precise and broadly accepted definition along with specific diagnostic criteria and above all, the awareness of physicians towards this entity."

Primary care physicians should refer patients early for cardiovascular assessment if they have established risk factors such as diabetes or obesity, or if they have symptoms that could be cardiovascular manifestations, such as shortness of breath, palpitations, and even fatigue or a reduced ability to exercise, Farmakis said. "Fatigue in an obese patient may not be just the effect of extra weight but a symptom of underlying HF," he said.

Ruschitzka noted that many attempts to control rhythm in patients with AF ultimately fail.

Doctors and researchers may need to focus on changes that can occur to the left atrium and consider more holistic approaches to treatment beyond ablation. "Ablation makes a lot of sense when we at the same time tackle the underlying precipitating factors," he said.

For primary care physicians, the proposed framework may be intuitive given their understanding of high blood pressure as a risk factor for AF, Ruschitzka added. "There is no atrial fibrillation without a cause," he said. "You have to think about what's underlying that."

Coats, Al-Khatib, Farmakis, and Ruschitzka have disclosed research funding from or other financial ties to pharmaceutical and medical device companies.

Eur Heart J. Published online December 7, 2021. Abstract

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