Seven factors predict a delayed diagnosis of cardiac amyloidosis

Abstract

Introduction: Diagnostic delay of cardiac amyloidosis (CAm) continues to challenge clinicians. We investigated features associated with delay and ascertained if a diagnostic delay had negative implications for the patient.

Methods: We performed a retrospective chart review identifying 82 subjects with biopsy-proven and mass-spectrometry-identified CAm with clinical and epidemiologic data including first potential symptom of amyloidosis. Pathology slides were scored for extent of amyloid. Robust statistical analyses including generalized linear and ordered logistic regression analysis were performed.

Results: There was a 22 month (median) delay in diagnosis, more pronounced (34 months) in subjects with transthyretin (ATTR) amyloidosis. Seven factors predict a delayed diagnosis including ATTR amyloid type (ratio =2.17, 95% CI 1.31–3.59), having carpal tunnel syndrome (2.13, CI 1.49–3.03) and age <70 at first symptom (1.85, CI 1.30–2.61). Individuals with delays of 1+ years had higher levels of NT proBNP (4451 vs. 2559 pg/mL, p = .016) and longer PR intervals (225 vs. 162 ms, p < .001) at the time of diagnosis.

Conclusions: Diagnostic delays negatively affect cardiac function. Of the predictive clinical features, carpal tunnel syndrome was frequent and its presence should lead to a more aggressive analysis for CAm in the appropriate clinical settings.

Keywords:

• Amyloid
• amyloidosis
• carpal tunnel
• heart
• transthyretin
• light chain amyloid

Disclosure statement

EB served as a consultant for Alnylam. DJ has served as a consultant for Alnylam, Eidos, GSK and Invitae. The other authors report no disclosures.