Table 2.

Summary of findings on delayed diagnosis/misdiagnosis of ATTR-CM

Diagnostic delay
ATTRwt-CM: median time to diagnosis 3.4 years (mean 6.1) ATTRv-CM: median time to diagnosis 2.6 years (mean 5.7)
Factors associated with diagnostic delay
Longer delay
Carpal tunnel syndrome (CTS)
Relative risk (RR) 4.6 (2.6–8.1) vs. no CTS [18]
CTS as the presenting symptom associated with longest delay (median 4.4 years) [28]
CTS present in 45% (15/33) of ATTRwt-CM patients with diagnostic delay > 3 months, vs. 18% (3/17) of those with a shorter delay (p = 0.07) [36]
ATTRwt-CM
RR 2.2 (1.4–3.4) vs. ATTRv-CM [18]
No family history of amyloid
Median 54.5 (IQR 26.1–94.5) vs. 24.5 (7.4–49.7) months with history; p = 0.0057 [18]
Predominant cardiomyopathy phenotype:
Median 53.1 (IQR 29.3–93.7) vs. 26.2 (9.4–59.0) months for mixed phenotype; p = 0.04 [18]
Mean 4 (SD 3.2) vs. 3 (2.0) years for mixed phenotype [33]
Mixed findings
Age
Mixed population: longer delay for age < 70 at symptom onset (RR 3.7 [2.1–6.6] vs. older) [18]
ATTRwt-CM: no association between age at diagnosis and delay [22]
ATTRv-CM: longer median delay for age at diagnosis ≥ 70 (3.4) vs. younger (2.2) [22]
Non-ATTR-CM diagnoses/misdiagnoses
34–57% of patients had previously received a non-ATTR-CM diagnosis for their symptoms  Two studies reported % of patients receiving specific misdiagnoses (note: some diagnoses overlap with ATTR-CM)
ATTRwt-CM [35]  Hypertensive cardiomyopathy: 12%  Hypertrophic cardiomyopathy: 8%  Ischemic heart disease: 4%  HFpEF: 3%  Aortic stenosis: 3%  Restrictive cardiomyopathy: 1%	Mixed ATTR-CM population [37]  HFpEF: 11.2%  Hypertensive heart disease: 10.3%  HFrEF: 5.2%  Hypertrophic cardiomyopathy: 5.2%  Ischemic heart disease: 2.6%  Aortic stenosis: 0.9%  Other (e.g. AF, AVB): 9.5%
Consequences of delay/misdiagnosis
More advanced symptoms at diagnosis (higher NYHA class) [36]  Adverse cardiac markers at diagnosis: higher NT-proBNP, prolonged ECG PR intervals, higher ECG intraventricular conduction delays, higher prevalence of atrial fibrillation [18]  Treatment for non-ATTR conditions [24]  Multiple invasive and noninvasive tests for other conditions [36]  Evaluation by multiple healthcare providers before diagnosis [3, 23, 24, 26]  Poor HRQoL at diagnosis [3]

AF atrial fibrillation, AVB atrioventricular block, CTS carpal tunnel syndrome, ECG electrocardiogram, ATTRv-CM hereditary transthyretin amyloid cardiomyopathy, HFpEF heart failure with preserved ejection fraction, HFrEF heart failure with reduced ejection fraction, HRQoL health-related quality of life, IQR interquartile range, NT-proBNP N-terminal pro B-type natriuretic peptide, NYHA New York Heart Association, RR relative risk, ATTRwt-CM wild-type transthyretin amyloid cardiomyopathy