Navigating the Frailty Factor in Atrial Fibrillation Management

In a new editorial, researchers discuss the impact of frailty on clinical decision-making in managing patients with atrial fibrillation and the prescription of oral anticoagulants.

Atrial fibrillation (AF) is a type of heart arrhythmia that occurs when the ​​heart’s electrical signals become irregular. This condition can increase the risk of stroke and heart failure, and becomes more common in older adults. Frailty is another condition that coincides with aging. Frailty encompasses an accumulation of deficits and can be defined as decreased physical function and resilience. For a significant proportion of the elderly population, both of these conditions coexist. This convergence can lead to additional health issues and further complicate the clinical landscape for aging individuals. 

“The impact of frailty on outcomes has not been previously well characterized in populations with AF.”

Studies on frailty and its overall impact on patients with AF are needed. In a new editorial paper, researchers Stephanie L. Harrison, Søren P. Johnsen and Gregory Y.H. Lip from Liverpool John Moores University and Liverpool Heart and Chest Hospital discuss some of the existing studies assessing frailty and AF in terms of patient outcomes and clinical decision-making. The researchers also discuss recommendations for clinical management of AF and frailty patients and include suggestions for future studies. On July 19, 2023, their editorial was published in Aging’s Volume 15, Issue 14, entitled, “The impact of frailty on the management of atrial fibrillation.”

Oral Anticoagulants for AF With Frailty: Yay or Nay?

Oral anticoagulants (OACs) are often prescribed to AF patients, as OACs aid in reducing blood clots and the risk of stroke. However, frailty patients are more susceptible to falls and therefore, more susceptible to bleeding risk. The prevention of blood clots is less than ideal for wound healing and can lead to impaired tissue repair, increased risk of infection and prolonged recovery times. Has frailty status impacted clinical decision-making when it comes to the prescription of OACs for AF patients?

“The impact of frailty on clinical decision making for managing patients with AF such as the prescription of oral anticoagulants (OACs) is unclear.”

In an effort to begin answering this question, the authors of this editorial reviewed a number of studies on frailty and AF. Some cross-sectional analyses revealed a significant association between frailty status and the prescription of OACs, while other studies found no such association. The authors explain that these dueling results may be due to differences in study populations, the tools/methods used to assess frailty and the timing of when the studies were conducted. The prescription of anticoagulants increased when a new class of OACs was introduced to the market.

Non-vitamin K antagonist oral anticoagulants (NOACs) were first introduced in the early 2010s. They are a class of drugs with significant advantages over traditional OACs, including less off-target effects, more predictable pharmacokinetics and a more targeted mechanism of action — making them a safer option for use in combination with other drugs. Notably, certain NOACs have specific reversal agents available, which can be used to rapidly reverse their anticoagulant effect in case of emergency. International guidelines recommended their use as a first-line treatment to reduce the risk of stroke in AF patients.

“Frailty alone should not be reason to withhold oral anticoagulation in patients with AF. In patients with frailty, the benefits of oral anticoagulation outweigh the small absolute risk of bleeding [6].”

Conclusions & Future Directions

The authors close the editorial by stating that additional research is needed to understand how frailty impacts clinical decision-making for the management of atrial fibrillation. They strongly suggest that frailty not be the sole reason AF patients are not prescribed potentially life-saving oral anticoagulants. There are more sensitive options available today, such as NOACs, that can potentially mitigate the drawbacks of anticoagulants for people with frailty. The authors also emphasize that pre-frailty assessments should be conducted for AF patients in order to reduce treatment risk and optimize the management of this condition.

“Assessment of pre-frailty in patients with AF and the development of strategies to address potentially modifiable components of pre-frailty to reduce the risk of frailty progression could have important implications to optimize care.”

Click here to read the full editorial published in Aging.

Aging is an open-access, peer-reviewed journal that has been publishing high-impact papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at

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Late-in-Life Interventions to Improve Cardiac Health

In a new research perspective, researchers discuss spermidine, rapamycin, caloric restriction, and exercise training to improve cardiac health in aging individuals.

Figure 1. Late-in-life exercise training boosts autophagic flux to an extent that rejuvenates cardiac function.
Figure 1. Late-in-life exercise training boosts autophagic flux to an extent that rejuvenates cardiac function.
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Cardiac dysfunction is a major public health concern. While it can occur for various reasons at any age, the prevalence of cardiac dysfunction dramatically increases with advancing age. Unfortunately, the underlying mechanisms of age-related cardiac decline are still largely unknown. Thus, it is essential for researchers to uncover novel strategies to improve cardiac health at advanced ages.

Autophagic Flux

An important physiological process involved in maintaining cardiovascular homeostasis is autophagic flux. Autophagic flux is the process by which cells break down and recycle their own cellular components after they have become damaged or unnecessary. This process is essential for maintaining healthy cardiac function, as it slows age-related oxidative damage, reduces the accumulation of toxic lipid and protein aggregates, and improves energy metabolism. However, the efficiency of autophagic flux decreases with age, resulting in declined cardiac function.

Given its crucial role and fading functioning, the search for strategies to improve autophagic flux may be essential for improving cardiovascular health as humans age. Researchers Jae Min Cho, Rajeshwary Ghosh, Sohom Mookherjee, Sihem Boudina, and J. David Symons from the University of Utah authored a new research perspective about nutraceutical, lifestyle and pharmacological interventions that can reduce age-associated cardiac dysfunction. On December 1, 2022, their research perspective was published in Aging’s Volume 14, Issue 23, entitled, “Reduce, Reuse, Recycle, Run ! : 4 Rs to improve cardiac health in advanced age.”

“In the following sections we review evidence that age-associated cardiac dysfunction can be Reduced by boosting cardiomyocyte autophagy (i.e., the ability to Reuse and Recycle damaged/dysfunctional proteins) via spermidine, rapamycin, and caloric-restriction. In addition, we highlight a new report indicating that a physiological intervention i.e., Running, rejuvenates cardiomyocyte autophagic flux to an extent that lessens age-associated cardiac dysfunction.”

Late-in-Life Interventions

Late-in-life interventions to improve cardiac health are particularly important since many of the world’s elderly populations are reaching advanced age with limited resources. This means that proven, inexpensive and accessible interventions to reduce cardiac dysfunction may have a profound impact on these populations. In this research perspective, the authors discuss four key interventions that reduce age-associated cardiac dysfunction: spermidine, rapamycin, caloric restriction, and exercise training. These interventions can reduce age-associated cardiac dysfunction by improving cardiac autophagy.

In October 2021, Cho et al. published a novel research paper about their study on late-in-life treadmill training in mice and its impact on autophagy, protein aggregates and heart function. The results of this study provided the first evidence that late-in-life exercise training can rejuvenate autophagic flux, clear protein aggregates and attenuate aging-associated cardiac dysfunction. In another murine study, researchers demonstrated that calorie restriction activates AMPK and increases the expression of autophagy-associated genes in the heart muscles.

Spermidine is a polyamine found in certain foods, such as legumes and nuts. A 2016 study linked spermidine to reduced age-associated cardiac dysfunction by attenuating cardiac hypertrophy and preserving diastolic function. Rapamycin is an mTOR inhibitor, immunosuppressant and anti-cancer drug. In a 2013 study, Flynn et al. were the first to report the cardiovascular effects of rapamycin in the context of aging. Rapamycin’s cardiovascular benefits include repressed pro-inflammatory signaling in heart muscles, reduced hypertrophy and preserved systolic function.


As the world’s population continues to age, it is increasingly important to identify interventions that can reduce age-associated cardiac dysfunction while avoiding high costs and potential side effects. In this research perspective, the researchers discussed evidence that spermidine, rapamycin, calorie restriction, and exercise training can improve autophagic flux and reduce age-associated cardiac dysfunction. While the mechanisms responsible for these improvements have yet to be fully elucidated, these strategies are cost-effective, accessible and relatively safe for elderly populations, and could provide a valuable way to improve cardiac health in advanced age.

“Findings from Cho et al. suggest that age-associated cardiac dysfunction can be re-established by Reducing (physical inactivity), Reusing (lysosomal degradation products e.g., amino acids for ATP synthesis), Recycling (damaged intracellular organelles via the lysosome and other protein degradation pathways), and Running (or increasing physical activity via any mode that can be enjoyed regularly and safely by the individual) (Figure 1).”

Click here to read the full research perspective published by Aging.

Aging is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

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