Enhancing Cardiovascular Care in Frailty: Priorities for Future Research

Frailty has become a key consideration in contemporary cardiovascular care due to its strong association with adverse health outcomes, altered responses to treatment, increased healthcare utilisation and reduced quality of life.1,2 As populations age and the prevalence of cardiovascular disease rises, healthcare professionals are increasingly encountering patients with varying degrees of frailty, making it essential to integrate frailty assessments into cardiovascular care.2,3 Frailty is a complex syndrome characterised by decreased physiological reserve, reduced resilience to stressors and increased vulnerability to functional decline, disability, hospitalisation and mortality.4 Its presence can greatly affect the clinical presentations, treatment outcomes and prognosis for patients with cardiovascular diseases.1,2 Recognising frailty is essential when making treatment decisions, stratifying risk and evaluating prognosis in patients with cardiovascular disease.4–6 The traditional disease-focused approaches may not adequately address the complex needs of frail individuals. Additionally, recognising frailty can help in the better allocation of healthcare resources, better communication with patients and their families regarding prognosis, expectations and shared decision-making.7

This special collection focuses on the current understanding of frailty and its effects on cardiovascular treatment. It includes five papers that cover topics such as cellular senescence, cardiovascular risk factors, heart failure and cardio-oncology.

‘The Biological Mechanisms of Frailty: Focusing on Cellular Senescence’ by Erusalimsky provides an overview of cellular senescence and discusses how the buildup of senescent cells in various organ systems disrupts tissue homeostasis, thereby increasing systemic inflammation and leading to functional decline.8 Cellular senescence has emerged as a central biological mechanism underpinning the pathophysiology of frailty, linking molecular ageing processes to systemic functional decline. Furthermore, the paper examines the potential of emerging interventions targeting the senescent cell burden and non-pharmacological approaches to mitigate frailty-associated functional decline. The clinical implications of linking cellular senescence to frailty are also discussed, and key priorities for future research aimed at improving risk stratification and therapeutic intervention are highlighted.

‘Frailty and Cardiovascular Risk’ by Evans et al. highlights the relationship between frailty and major conventional vascular risk factors, and their inter-relationships.9 The paper discusses the impact offrailty on managing and treating vascular risks and outlines the implications for both research and clinical care aimed at reducing the burden of cardiovascular disease in frail individuals. Improving cardiovascular health across the lifespan is associated with a reduced risk of frailty. Therefore, optimising vascular risk factors is crucial for promoting healthy ageing, as it not only reduces the likelihood of cardiovascular events but also helps prevent the onset of frailty.

Frailty is common in individuals with heart failure. Many patients with heart failure and frailty are prescribed suboptimal medication regimens and may not receive treatments that align with established guidelines, resulting in poorer functional recovery and increased mortality.10 In response to this, frailty has increasingly been incorporated into clinical guidelines for managing heart failure. Recent guidelines from the European Society of Cardiology, the American College of Cardiology, the National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand emphasised the importance of assessing frailty to guide personalised treatment strategies.11–13

In the paper ‘Clinical Pharmacology of Heart Failure in Frailty’ in this special collection, Duong et al. discuss the challenges of optimising pharmacotherapy for patients with heart failure and frailty.14 The authors consider how physiological changes in individuals with heart failure and frailty can influence the clinical pharmacology of heart failure medications. Specifically, the paper addresses pharmacodynamics, pharmacokinetics and sex-specific differences, as well as adverse events and withdrawal effects associated with these treatments. There is limited understanding of the clinical pharmacology of heart failure therapies in people living with frailty, highlighting the necessity for more representative enrolment of this population in clinical trials.

Frailty is frequently seen as a clinical syndrome associated with ageing. However, cancer and its treatments can adversely affect patients’ physiological capacity, hasten the ageing process and result in an earlier development of frailty syndrome. This special issue features two key contributions that emphasise the importance of frailty in the field of cardio-oncology. The articles ‘Frailty Meets cardio-oncology: A New Frontier in Personalised Cancer Care’ by Ilaria et al. and ‘The Role of Frailty in Cardio-oncology and its Challenges’ by Amsalu et al. provide timely and informative insights into the significance of frailty assessment in cardio-oncology.15,16 Both papers offer detailed information on the pathophysiology of frailty within the context of cardio-oncology, as well as the common frailty assessment tools used in cancer populations. Ilaria et al. concentrate on recent studies that investigated the connection between frailty and cardiotoxicity, highlighting how frailty assessment and management could enhance patient care in cardio-oncology, while Amsalu et al. address the challenges associated with frailty assessments in this field and the current gaps in cardiovascular risk assessment tools for older cancer patients.

The evidence presented in the papers in this collection emphasises the critical need for comprehensive frailty assessment and early identification of frailty among older adults. These papers highlight not only the prevalence of frailty, but also its significant impact on health outcomes, advocating for its integration into routine clinical care. By embedding frailty assessment within standard healthcare practices, clinicians can proactively manage risk factors and improve patient outcomes.

A recurring theme across these papers is the necessity for a robust future research agenda focused on enhancing howfrailty is identified, measured, treated and managed clinically. This involves a call for more representative studies that offer nuanced insights into the various manifestations of frailty, along with targeted interventions tailored to individual patient needs. Given that frailty is inherently heterogeneous, a one-size-fits-all approach is inadequate. Individualised strategies that consider the unique circumstances and health conditions of older adults are essential for effective management.

The authors highlighted the importance of patient-centred outcomes and goal attainment measures that align with the values and preferences of older individuals. By incorporating what matters most to patients, healthcare providers can ensure that interventions are meaningful and impactful. It is equally vital to investigate how responses to treatment can differ across varying levels of frailty, further underscoring the need for personalised care. In summary, these papers collectively highlight several key priorities for future research directions in the field of frailty and cardiovascular care:

1. develop reliable biological and functional frailty biomarkers;

2. conduct longitudinal studies to clarify causal mechanisms, particularly those related to cellular senescence;

3. design and test multidimensional interventions, which may include senotherapeutics, lifestyle modifications and rehabilitation programmes;

4. ensure that frail older adults are adequately represented in clinical trials and medication studies; and

5. adopt personalised, frailty-centred approaches that emphasise outcomes significant to older adults and support healthy ageing.

The future of frailty research should pivot towards precision medicine, where clinical interventions are carefully aligned with the biological, clinical and functional characteristics of individuals. This holistic approach aims to transform frailty from a condition often recognised after its onset into a state that can be detected early, closely monitored, effectively prevented and possibly reversed. Overall, these initiatives aim to enhance the quality of life for older adults, ensuring they receive the support needed to maintain their health and independence.