In the study conducted by Garmendia et al. (1) the objective was to determine the prevalence of hypoalbuminemia and its clinical impact in patients with severe aortic stenosis treated with TAVI. This was a single-center, retrospective study where the baseline characteristics were analyzed based on the presence or absence of hypoalbuminemia (albumin levels < 3.5 g/dL) plus an overall survival study using the Kaplan-Meier estimator.

Albumin discrimination abilities to predict overall mortality using the ROC curve and its area were studied. The prevalence of hypoalbuminemia was 18.3%. A very important piece of information in this study is the higher overall mortality rate in patients with hypoalbuminemia (25.5% vs 6.0%; P = .002). Albumin showed modest discrimination abilities of 0.715% regarding the overall mortality rate and a greater discrimination cut-off value of 3.81 g/dL.

Currently, we use well-established surgical risk scores in candidates eligible for TAVI to stratify such risk in patients with severe aortic stenosis like the European System for Cardiac Operative Risk Evaluation (EuroSCORE 1 and 2) and the Society of Thoracic Surgeons (STS) (2,3). Both these scores were developed to predict the procedural mortality and morbidity rates of patients referred for cardiac surgery.

The capacity of these scores to predict disease progression is limited because they don’t include frailty.

How can frailty be defined? It is defined as a reduced capacity to recover in pathological or iatrogenic situations due to the weakness associated with old age (4). This concept of frailty is very important because it can be applied to all invasive procedures where the disease progression of frail patients is poor (5).

Most in-hospital reports of TAVI confirm procedural successes in over 95% of the cases. However, 2 out of 5 patients from the PARTNER I (Placement of AoRTic traNscathetER valve trial), and early studies with CoreValve revealed a low quality of life or a low 1-year mortality rate (6).

Regarding TAVI, it seems obvious that frailty damages patient progression significantly (7,8). To complement the risk scores, the Valve Academic Research Consortium (VARC) 2 established that we should use other anatomical and biological tools to assess risk and disease progression, being frailty one of the most important ones. The other one recommended is albumin as a biological marker (9).

In a former study conducted by Segev et al., in isolation, albumin has predictive value regarding prognostic assessments within the same TAVI procedure. (10)

In the following study conducted by the same group (1), researchers added albumin to the STS and EuroSCORE-2 to predict mortality in 426 patients treated with TAVI and studied retrospectively. Patients were divided into 4 groups based on their levels of albumin (4 g/dL), STS score (4.5%), and EuroSCORE-2 (3.45%) (high vs low). Patients with hypoalbuminemia had a higher mortality rate. However, those with hypoalbuminemia and high STS or EuroSCORE had higher mortality rates. In conclusion, adding albumin to conventional risk scores improved their predictive value to assess 1-year mortality. After adjusting the scores, hypoalbuminemia remained a strong independent predictive factor of 1-year mortality. Even patients with elevated albumin levels had better prognoses regardless of the results of their early risk scores. Mortality difference starts immediately after the procedure and grows progressively within the first 4 months after TAVI.

Based on these data, the objective assessment of frailty to optimize patient selection is strongly advised. However, there is no strong consensus on how to assess frailty. At the same time, this lack of consensus is the reason why it is not assessed in the routine daily practice. Walking speed is one of the methods most widely used. However, using this resource alone undermines the specificity needed to discriminate complex patients who will have poor disease progression after TAVI (12,13).

The Frailty-AVR trial (14) compared the predictive value of 7 different scales as predictors of poor disease progression after TAVI or surgical aortic valve replacement. One of these methods is the Essential Frailty Toolset (EFT) that basically assessed the muscle strength of lower limbs, cognitive impairment, and anemia with the following cut-off values: 13 g/dL for men, and 12 g/dL for women. The albumin cut-off value was 3.5 g/dL. The endpoints were all-cause mortality and 1-year disability after the procedure. This prospective study was conducted in 14 centers from 3 different countries and included 1020 patients with a mean age of 82 years. Depending on the scale used, frailty went from 26% up to 68%. The most powerful predictor of 1-year mortality was the EFT. As a matter of fact, it was the strongest predictor of worsening disability and 30-day mortality. This is the largest comparative study of frailty scores in the TAVI or surgical aortic valve replacement setting. Although the possibility of success of both procedures was very high, the rate of 1-year functional impairment was 35% for all patients and > 50% for those considered frail. Inflammatory markers are elevated in these patients, which is indicative of a biological connection between inflammation and frailty (15).

In conclusion, this study conducted by Garmendia et al. shows how important it is to assess albumin prior to perform TAVI. Also, it replicates former studies conducted in our setting as a good expression of the scientific method. There is no doubt that hypoalbuminemia is an expression of frailty, which is a huge risk factor for disability and mortality.

Dr. Carlos Fernández-Pereira, PhD FACC, MD
Interventional Cardiologist
Scientific Secretary
Argentine College of Interventional Cardioangiologists (CACI)

1. Garmendia CM, Chiabrando JG, Medina de Chazal H, et al. Impacto clínico de la hipoalbuminemia en pacientes con estenosis aórtica severa sometidos a reemplazo valvular aórtico percutáneo. Revista Argentina de Cardioangiología Intervencionista. Agosto 2022, vol 3 en prensa doi10.30567/RACI/202203/00 -00.

2. O’Brien SM, Shahian DM, Filardo G, et al. The Society of Thoracic Surgeons 2008 Cardiac Surgery Risk Models: Part 2-Isolated Valve Surgery. Ann Thorac Surg [Internet]. 2009 Jul [cited 2020 Aug 8];88(1 Suppl.)

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5. Buchner DM, Wagner EH. Preventing frail health. Clin Geriatr Med 1992;8:1-17.

6. Lindman BR, Alexander KP, O’Gara PT, Afilalo J. Futility, benefit, and transcatheter aortic valve replacement. JACC Cardiovasc Interv 2014;7:707-16.

7. Kamga M, Boland B, Cornette P, et al. Impact of frailty scores on outcome of octogenarian patients undergoing transcatheter aortic valve implantation. Acta Cardiol 2013;68:599-606.

8. Green P, Woglom AE, Genereux P, et al. The impact of frailty status on survival after transcatheter aortic valve replacement in older adults with severe aortic stenosis: A single-center experience. JACC Cardiovasc Interv 2012;5:974-81.

9. Kappetein AP, Head SJ, Genereux P et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: The Valve Academic Research Consortium-2 consensus document (VARC-2). Eur J Cardiothorac Surg 2012;42:S45-S60.

10. Bogdan A, Barbash IM, Segev A, et al. Albumin correlates with all-cause mortality in elderly patients undergoing transcatheter aortic valve implantation. EuroIntervention 2016.

11. Grossman Y, Barbash I, Fefer P, et al. Addition of albumin to Traditional Risk Score Improved Prediction of Mortality in Individuals Undergoing Transcatheter Aortic Valve Replacement. DOI: 10.1111/jgs.15070. J Am Geriatr Soc 2017.

12. Afilalo J, Kim S, O’Brien S, et al. Gait speed and operative mortality in older adults following cardiac surgery. JAMA Cardiol 2016;1:314-21.

13. Alfredsson J, Stebbins A, Brennan JM, et al. Gait speed predicts 30-day mortality after transcatheter aortic valve replacement: results from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Circulation 2016;133:1351-9.

14. Afilalo J, Lauck S, Kim DH, et al. Frailty in Older Adults Undergoing Aortic Valve Replacement. The FRAILTY-AVR Study. JACC Vol. 70, Nº 6, 2017 August 8;2017:689-700.

15. Sousa ACPA, Zunzunegui MV, Li A, Phillips SP, Guralnik JM, Guerra RO. Association between C-reactive protein and physical performance in older populations: results from the International Mobility in Aging Study (IMIAS). Age Ageing 2016;45:274-80.

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