Managing
ATTR‑CM
A New Era in Managing ATTR‑CM
The ATTR‑CM Clinical Landscape Has Evolved in Recent Years1
Years
Average Symptom Duration Pre-diagnosis
Years
Class III/IV
More likely
Heart Failure Severity at Diagnosis
Class I/II
More likely
Year
Median Survival Post-diagnosis*
Years
In 2012, 99mTc-DPD scintigraphy became a routine part of the diagnostic algorithm for ATTR‑CM.2
*Median survival during 2002 to 2012 ranged from 35 to 39 months and during 2012 to 2021 from 53 to >60 months.
Early diagnosis and intervention are critical to slowing ATTR‑CM progression and prolonging quality of life3-6
Diagnosis of transthyretin amyloid cardiomyopathy (ATTR‑CM)* has exponentially increased over the last decade due to enhanced awareness, an evolution in the standard of care, and the development of a noninvasive diagnostic algorithm.2,3,7 These advances have significantly improved survival, but many people continue to manage cardiac morbidity and diminishing quality of life.2,8,9 More effective treatment options are needed.
*Also known as ATTR cardiomyopathy, or ATTR cardiac amyloidosis (ATTR‑CA).
Monitoring Disease Progression
As understanding of ATTR‑CM progression and opportunities for earlier intervention have grown, goals for patient management have expanded beyond prolonging survival to include:3,10
- Maintaining quality of life10
- Preserving independence10
- Keeping patients out of the hospital10
- Stabilization or improvement of prognostic biomarkers10
Protecting the Moments That Matter
The progression of ATTR‑CM deprives people of their strength, mobility, and independence. At later stages of disease, those affected may lose their ability to engage in previously enjoyable activities or perform routine activities such as household chores and self-care.2,12-14
Common clinical measures of functional capacity and quality of life for people with ATTR‑CM include:
The 6-minute Walk Test (6MWT)10,15,16
A practical measure of functional capacity that correlates with quality of life and prognosis:
- Measures the distance a person can walk at their own pace on a flat, hard surface over a period of 6 minutes
- Declines in 6-minute walk distance have been associated with increased levels of NT-proBNP, a prognostic biomarker for ATTR-CM progression
The Kansas City Cardiomyopathy Questionnaire (KCCQ)2
A 23-item questionnaire that examines:
- Physical function
- Independence
- Symptom frequency and severity
- Social function
- Limitations to quality of life
Biomarkers May Predict ATTR‑CM Outcomes
N‐terminal pro‐B‐type natriuretic peptide (NT-proBNP) and serum transthyretin (TTR) are emerging as important predictive biomarkers for mortality and risk of acute heart failure in people with ATTR‑CM.11,17,18
High Serum TTR: An Indicator of Stability
High Levels of Serum TTR Are Associated With Protection Against Heart Failure19
Reproduced with permission from Greve AM, et al. JAMA Cardiol. 2021;6(3):258-266. Copyright©(2021) American Medical Association. All rights reserved.
High Levels of Serum TTR Are Associated With Prolonged Survival11
Reproduced with permission from Hanson JLS, et al. Circ Heart Fail. 2018;11(2):e004228.
NT-proBNP: An Indicator of Cardiac Morbidity
- Secreted by the heart in response to stress and pressure overload18
- Measure of worsening heart failure and cardiac dysfunction17,18
12-Month Change in NT-proBNP: One of the Only Independent Predictors of ATTR‑CM Mortality17
| Variable | HR (95%CI) | P value |
|---|---|---|
| ∆ NT-proBNP (ng/L)* | 1.05 (1.02-1.07) | 0.001 |
| ∆ eGFR (mL/min) | 1.00 (0.98-1.01) | 0.732 |
| ∆ Albumin (g/L) | 1.01 (0.95-1.06) | 0.840 |
| ∆ Troponin T (ng/L) | 1.01 (1.00-1.02) | 0.055 |
| Increasing NYHA class | 1.72 (1.18-2.52) | 0.005 |
| ∆ 6MWT (m)† | 0.85 (0.70-1.02) | 0.080 |
| *HR for NT-proBNP is per 500 ng/L increase †HR for 6MWT distance is per 100 m increase |
||
6MWT, 6-minute walk test; eGFR, estimated glomerular filtration rate; HR, hazard ratio; NT-proBNP, N‐terminal pro‐B‐type natriuretic peptide; NYHA, New York Heart Association.
Decreased NT-proBNP Is Associated With Increased Survival in People With ATTR‑CM17
Adapted from Law S, et al. Heart. 2022;108(6):474-478. Data courtesy of UK National Amyloidosis Centre.
Ioannou A, et al. Impact of Earlier Diagnosis in Cardiac ATTR Amyloidosis Over the Course of 20 Years. Circulation. 2022;146(22):1657-1670. 2. Lane T, et al. Natural History, Quality of Life, and Outcome in Cardiac Transthyretin Amyloidosis. Circulation. 2019;140(1):16-26. 3. Kittleson MM, et al. American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology. Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement From the American Heart Association. Circulation. 2020;142(1):e7-e22. 4. Rozenbaum MH, et al. Impact of Delayed Diagnosis and Misdiagnosis for Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM): A Targeted Literature Review. Cardiol Ther. 2021;10(1):141-159. 5. Rozenbaum MH, et al. Estimating the health benefits of timely diagnosis and treatment of transthyretin amyloid Cardiomyopathy. J Comp Eff Res. 2021;10(11):927-938. 6. Griffin JM, et al. ATTR Amyloidosis: Current and Emerging Management Strategies: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2021;3(4):488-505. 7. Gillmore JD, et al. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016;133(24):2404-12. 8. Miller AB, et al. Causes of Cardiovascular Hospitalization and Death in Patients With Transthyretin Amyloid Cardiomyopathy (from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial [ATTR-ACT]). Am J Cardiol. 2021;148:146-150. 9. Hanna M, et al. Impact of Tafamidis on Health-Related Quality of Life in Patients With Transthyretin Amyloid Cardiomyopathy (from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). Am J Cardiol. 2021;141:98-105. 10. Garcia-Pavia P, et al. Diagnosis and Treatment of Cardiac Amyloidosis. A Position Statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur J Heart Fail. 2021;23(4):512-526. 11. Hanson JLS, et al. Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin. Circ Heart Fail. 2018;11(2):e004000. 12. Rintell D, et al. Patient and Family Experience with Transthyretin Amyloid Cardiomyopathy (ATTR-CM) and Polyneuropathy (ATTR-PN) Amyloidosis: Results of Two Focus Groups. Orphanet J Rare Dis. 2021;16(1):70. 13. Stewart M, et al. Characterizing the High Disease Burden of Transthyretin Amyloidosis for Patients and Caregivers. Neurol Ther. 2018;7(2):349-364. 14. Nativi-Nicolau J, et al. Natural History and Progression of Transthyretin Amyloid Cardiomyopathy: Insights from ATTR-ACT. ESC Heart Fail. 2021;8(5):3875-3884. 15. Solway S, et al. A Qualitative Systematic Overview of the Measurement Properties of Functional Walk Tests Used in the Cardiorespiratory Domain. Chest. 2001;119(1):256-70. 16. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS Statement: Guidelines for the Six-Minute Walk Test. Am J Respir Crit Care Med. 2002;166(1):111-7. 17. Law S, et al. Change in N-terminal Pro-B-type Natriuretic Peptide at 1 Year Predicts Mortality in Wild-Type Transthyretin Amyloid Cardiomyopathy. Heart. 2022;108(6):474-478. 18. Oghina S, et al. Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide and High-Sensitivity Troponin T Levels in the Natural History of Transthyretin Amyloid Cardiomyopathy and Their Evolution after Tafamidis Treatment. J Clin Med. 2021;10(21):4868. 19. Greve AM, et al. Association of Low Plasma Transthyretin Concentration With Risk of Heart Failure in the General Population. JAMA Cardiol. 2021;6(3):258-266.
The information provided on this site is intended for use by healthcare professionals practicing in the United States.
By clicking ENTER you confirm you are a healthcare professional practicing in the United States.