Undergraduate Student St. Paul's Hospital Vancouver, British Columbia, Canada
Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure (HF) in the elderly population. The diagnostic pathway for ATTR-CM typically begins at the onset of HF symptoms or with the incidental finding of increased left ventricular wall thickness, when this infiltrative disease may have already caused extensive damage to the myocardium. Identifying early clinical manifestations of ATTR-CM may help clinicians to create a pathway for diagnosing this disease in its earlier stages.
METHODS AND RESULTS: We developed a 3-year prospective observational registry, collecting detailed medical histories and clinical characteristics for 200 participants who were suspected of having amyloid cardiomyopathy and referred for pyrophosphate scintigraphy. Participants were divided into two groups based on whether they were diagnosed with ATTR-CM or not and their clinical characteristics were compared. We then aimed to identify non-cardiac medical conditions associated with ATTR-CM that preceded both the date of ATTR-CM diagnosis and onset of cardiac symptoms. Chi-squared tests and paired t-tests were used to calculate differences between groups.
Forty-six (23.0%) referred patients had a clinical diagnosis of ATTR-CM, while 154 (77.0%) had non-ATTR-CM diagnoses. Bilateral carpal tunnel syndrome (CTS) was more strongly associated with ATTR-CM diagnosis than with non-ATTR-CM (69.6% vs. 14.3%, p < 0.001). The mean onset time of CTS was 9.2 ± 6.5 years before ATTR-CM diagnosis. Similarly, spinal stenosis was significantly more prevalent in ATTR-CM participants (56.5% vs. 9.1%, p < 0.001), as was arthropathy of large joints (63.0% vs. 22.1%, p < 0.001) and spontaneous ligament rupture (26.1% vs. 7.1%, p = 0.001), with mean onset times of 6.9 ± 6.0, 8.0 ± 7.0, and 9.4 ± 7.1 years before ATTR-CM diagnosis, respectively. In contrast, initial cardiac symptoms, particularly atrial fibrillation and HF, occurred just 2.9 ± 2.0 and 1.9 ± 2.2 years before ATTR-CM diagnosis. Overall, the mean onset time of the identified non-cardiac medical conditions was significantly earlier than the onset of initial cardiac symptoms (8.3 ± 5.0 years vs. 2.6 ± 2.4 years, p < 0.001).
Conclusion: Our data highlights four non-cardiac medical conditions associated with ATTR-CM that manifest before the initial cardiac symptoms of the disease. To build upon these findings, further research is needed to evaluate the value and feasibility of using the identified conditions and other characteristics for early detection of ATTR-CM.
