Figure 1
Top arrow represents a conceptual diagram of progression across time from a normal heart to advanced transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM). Bottom arrow depicts different opportunities during the disease process for earlier detection of ATTR-CM. abnl: abnormalities; pAF: paroxysmal atrial fibrillation; DOE: dyspnea on exertion; NT-proBNP: N-terminal pro-brain natriuretic peptide; EHR: electronic health record
Note: this diagram is meant to be conceptual, and manifestations of disease may vary across the spectrum of wall thickness.
* Conduction abnormalities include first-degree heart block, right bundle branch block (BBB), left BBB, intraventricular conduction delay, complete heart block.
** High-risk subpopulations: specialized heart failure clinics, inpatient heart failure admissions, transcatheter aortic valve replacement, Black patients.
Figure 2
Past medical/surgical history and symptoms that can serve as red flags to raise clinical suspicion for cardiac amyloidosis.
Figure 3
Representation of echocardiographic images (parasternal long-axis view) at different levels of wall thickness in transthyretin amyloid cardiomyopathy. The ideal therapeutic window would be to identify these patients at the earliest stage possible with near normal or mildly increased wall thickness before decline in quality of life, elevation in cardiac biomarkers, and overt cardiac manifestations of disease.15 NAC: National Amyloidosis Center; MRI: magnetic resonance imaging; Echo: echocardiography; EKG: electrocardiogram; NTproBNP: N-terminal-pro hormone brain natriuretic peptide; TTR: transthyretin
Figure 4
A case of early diagnosis and initiation of treatment in asymptomatic transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) through proactive tissue screening. A 73-year-old White female underwent carpal tunnel release surgery; Congo red staining of removed tenosynovial tissue was amyloid (+), typed as ATTR by mass spectrometry. TTR genetic testing revealed Ala 81Thr variant (+). At baseline, echocardiography with strain, N-terminal pro-brain natriuretic peptide (NT-proBNP), and 99mTc-PYP scan showed no evidence of cardiac amyloid. At 4-year follow-up (age 77), the patient remained asymptomatic, with minimal to no change on echo and NT-proBNP, but she developed grade 3 diffuse uptake on 99mTc-PYP scan. After shared decision making, the patient was started on tafamidis.
Figure 5
Cleveland Clinic institutional algorithm for tenosynovial biopsy during carpal tunnel release surgery utilizing a two-tier approach to select patients for prospective Congo red staining. If positive, further amyloid typing with mass spectrometry is performed and a referral is made to an amyloid specialist.29 TCL: transverse carpal ligament
Figure 6
Strategies and tools to detect asymptomatic transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) earlier in the disease course. Patient and clinician engagement/education, tissue screening, biomarkers and gene biobanks, and analyses of clinical data derived from the electronic health records, longitudinal registries, and clinical trials can be used to calibrate the optimal use of diagnostic tools (ie, targeted questionnaires, electrocardiogram, echocardiography, cardiac magnetic resonance imaging, cardiac scintigraphy, cardiac biomarkers). Over time, learning algorithms using machine learning and artificial intelligence may allow for the iterative improvement of accurate diagnosis and enable patient identification and appropriate screening of patients at risk for ATTR-CM. EHR: electronic health record