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Transthyretin amyloidosis results from transthyretin misfolding and the subsequent formation of amyloid fibrils that can accumulate in some organs, including the heart.¹ Transthyretin cardiac amyloidosis (ATTR-CA) affects those with heart failure and patients undergoing percutaneous aortic valve replacement, both associated with aging, and is also associated with increased hospitalization for heart failure.^2-4

Little research has characterized frailty and its prognostic significance among elderly patients with ATTR-CA. Although the Comprehensive Geriatric Assessment (CGA) is currently the best tool to help manage frailty, the use of multiple scores makes this approach time-consuming and often difficult, some reports say.⁵

Reasoning that a rapid frailty screening test as a component of integrative care would be beneficial in the ATTR-CA patient population, researchers in France compared the clinical, biological, and transthoracic echocardiography (TTE) characteristics of older individuals with ATTR-CA according to the G8 geriatric frailty screening tool.¹ Originally developed to help assess frailty in older people with cancer, the G8 score has also been previously evaluated in those with certain cardiac conditions.⁶

鈥淥ur study is the first to use the G8 score in ATTR-CA patients,鈥� St茅phanie Cazalbou, from the Department of Cardiology at the University Hospital of Toulouse in France, and colleagues wrote in their report, published recently in the Journal of Clinical Medicine.¹

鈥淐ardiac amyloid burden is associated with frailty according to the G8 score in ATTR-CA patients and is associated with an impaired prognostic score,鈥� the authors concluded. 鈥淓xploration of patients with ATTR-CA over 75 years old using the G8 score should be considered to implement targeted interventions.鈥�¹

G8 in ATTR-CA

The investigators included patients 75 years or older who were confirmed to have ATTR-CA during a cardiac assessment from January 2020 through April 2021 at Toulouse University Hospital in France. TTE as well as functional evaluations based on a 6-minute walking distance test (6MWD) or cardiopulmonary exercise testing (CPET) were performed. Routine blood tests, along with genetic analyses to determine wild-type ATTR-CA and variant ATTR-CA, were also conducted.

The activities of daily living (ADL) score and the G8 score were used for geriatric assessments among all participants to determine their frailty status. The G8 score consists of 8 questions on:

• diet over the previous 3 months
• weight loss within the previous 3 months
• mobility 
• neuropsychological issues
• body mass index
• taking more than 3 prescription medications each day
• self-rated health status 
• age

The total G8 score ranges from 0 to 17, with a higher score reflecting a better health status. A G8 score of 14 or less indicates the person is at risk of frailty, the researchers pointed out, in which case a geriatrician should then conduct a CGA for a more complete evaluation. The authors also noted that the G8 screening tool has been validated in geriatric oncology, but not in cardiovascular diseases. 

Prognosis was analyzed using the staging system for ATTR-CA proposed by Gillmore et al4; demographic and clinical data were obtained from electronic medical records.

ATTR-CA characteristics by G8-identified frailty

The study included 52 ATTR-CA patients (mean age of 84 years), including 42 (80%) males. The study group was primarily independent, as indicated by a mean ADL score of 5.5 and an ADL score of 鈮�3 for 96% of patients. Overall, 75% were considered to be frail according to the G8 score.

Mean New York Heart Association stage was more severe in frail vs non-frail patients (2.2 vs 1.7; P=.004) and 62% of frail patients versus 23% of non-frail patients had a poor prognosis, as indicated by a Gillmore stage of 2 or 3 (P=.05). The investigators found global left ventricular strain to be lower (鈭�11.7% vs 鈭�14.9%; P=.014) and the interventricular septum to be thicker (18 mm vs 17 mm; P=.033) in frail patients compared to those who were not frail. 

No significant differences according to the G8 score were apparent in left ventricular ejection fraction and diastolic function or right ventricular systolic function. Significant differences between frail and non-frail patients in functional tests also were not evident on the basis of the G8 score. The authors pointed out that the absence of a significant difference between frail and non-frail patients in 6MWT 鈥渟hows that this functional test may not be sufficiently discriminative when identifying symptomatic older patients, unlike the NYHA classification.鈥�

Clinical comments

The majority of older patients with ATTR-CA are considered to be frail based on the G8 screening tool and frail patients with ATTR-CA are more symptomatic, have more cardiac involvement, and have a poorer prognosis, which necessitates more personalized cardiac care, the authors summarized.

Although older patients with ATTR-CA were found to have a high prevalence of frailty, they were considered independent based ADL scores, 鈥渨hich could mislead cardiologists into thinking they are fit,鈥� the authors wrote. 鈥淐onsequently, screening for geriatric impairments with the G8 score seems interesting and could help cardiologists identify patients requiring further CGA.鈥� 

Caveats

The authors did note in their study that a smaller sample size was the main limitation of their study. They also wrote that the G8 score has not yet been validated for use in scoring cardiovascular disease. Michel G. Khouri, MD, Cardiologist, Advanced Heart Failure Specialist, and Transplant Cardiologist at Duke Health, Durham, NC, who was not involved with the research, commented on the report. 鈥淭he findings will need to be validated in a larger ATTR-CA cohort before they can be generalized,鈥� Dr. Khouri told 番茄社区app, 鈥渂ut the concept of using a simple clinical assessment tool for frailty is intriguing.鈥� 

鈥淔railty is a strong prognostic predictor over the general spectrum of cardiovascular disease,鈥� he added, 鈥渁nd is also likely an effective integrative measure of the clinical decline associated with disease progression in ATTR-CA. These findings demonstrate that, besides being feasible in the ambulatory setting, the G8 frailty screening tool has potential to improve clinicians'' 'ability to identify higher-risk ATTR-CA patients who might benefit from more individualized therapeutic management.鈥�

Published: January 30, 2024