Updated ATTR-CM Criteria Standardize Disease Progression Monitoring

A recent position statement presents updated criteria for transthyretin amyloid cardiomyopathy (ATTR-CM) monitoring, combining clinical, biomarker, functional, and quality of life measures to track disease progression in patients with ATTR-CM.1

Heart examination | Image credit: Ngampol - stock.adobe.com

The guidance was developed by an international panel of experts and is published in JACC: Heart Failure.

"There is evidence supporting the prognostic value of each parameter within the proposed criteria, and these measures should be integrated into routine clinical monitoring to better assess disease progression in patients with transthyretin amyloid cardiomyopathy," study author Pablo García-Pavía, MD, PhD, head of the Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, at the Hospital Universitario Puerta de Hierro in Madrid, Spain, wrote in a statement.2

The criteria were developed through a structured review of published evidence and expert consensus. The panel of experts considered prior monitoring frameworks, including the 2021 guidance, and evaluated the prognostic value, reproducibility, and feasibility of individual parameters. These parameters were selected based on their ability to capture meaningful changes in cardiac function, clinical events, and patient-reported outcomes.

The aim of the study was to create a practical, multidimensional framework suitable for routine clinical practice while supporting standardized follow-up across centers and studies.1

The updated criteria include 6 measurable parameters recommended for tracking disease progression over a 12-month period:

• Heart failure–related hospitalization, which identifies clinical worsening events requiring urgent care.
• Outpatient diuretic intensification, which tracks increasing symptomatic volume management.
• N-terminal pro-B-type natriuretic peptide, which reflects cardiac stress and disease activity.
• Estimated glomerular filtration rate, which assesses renal function, and can be affected by cardiac amyloidosis.
• The 6-minute walk test, which evaluates functional capacity and exercise tolerance over time.
• Quality of life measures, such as the Kansas City Cardiomyopathy Questionnaire or NYHA class, which captures the patient-reported impact of disease progression.

Additionally, the consensus, progression is defined when 2 or more parameters meet prespecified thresholds over 12 months, comparing results with the preceding year rather than the baseline to reduce the effect of random variability. The position statement notes that integrating multiple parameters allows clinicians to identify meaningful changes in disease status while minimizing false-positive signals from single measures.2

“The proposed approach emphasizes that disease progression should be determined by changes across several parameters rather than a single measure to ensure accurate detection of clinically relevant worsening," wrote the authors of the study.1

However, the researchers acknowledged some limitations. Although each parameter has prognostic evidence, the proposed criteria have not yet been validated to determine whether progression, as defined, should prompt changes in disease-modifying therapy. Therefore, the researchers noted that prospective studies are needed to evaluate whether applying these monitoring criteria improves patient outcomes.

Despite these limitations, the researchers believe the proposed criteria provide a standardized approach for longitudinal monitoring in ATTR-CM, integrating clinical events, biomarkers, functional performance, and patient-reported outcomes. By requiring progression to meet thresholds in multiple parameters over a year, the framework distinguishes meaningful clinical change from random variability. Furthermore, the position statement emphasizes that consistent monitoring may improve comparability across clinics and studies, providing a foundation for future research and clinical decision-making in patients with ATTR-CM.

"Future studies should investigate whether changes in ATTR-CM disease-modifying treatment improve outcomes in patients demonstrating disease progression, as the proposed criteria are intended to standardize monitoring but not to dictate treatment decisions at this stage,” wrote the authors.

References

1. García-Pavía P, Witteles R, Damy T, Maurer MS, et al. Monitoring disease progression in patients with transthyretin amyloid cardiomyopathy. JACC Heart Fail. doi:10.1016/j.jchf.2025.102766
2. New proposed criteria for monitoring disease progression in ATTR-CM. ACC Journal Scan. December 10, 2025. Accessed February 4, 2026. https://www.acc.org/Latest-in-Cardiology/Journal-Scans/2025/12/09/16/51/New-Proposed-Criteria-For-Monitoring-Disease-Progression-in-ATTR-CM