Trends in diagnosis, referral, red flag onset, patient profiles and natural outcome of de novo cardiac amyloidosis and their multidisciplinary implications

Abstract

Background

Cardiac amyloidosis (CA) is often overlooked or misdiagnosed. Effects of growing disease awareness, diagnostic ameliorations and novel treatment options on CA diagnosis and management are scarcely reported.

Objective

To report trends in diagnosis, referral routes, clinical presentation, early onset diagnostic red flags and outcome in de novo CA subjects.

Methods

An unselected cohort of 139 de novo CA patients over an 8-year period in a tertiary referral hospital was recruited.

Results

Transthyretin (ATTR, 82%, n = 114) was the most common CA form; Light-chain (AL, 15%, n = 21) and secondary (AA, 3%, n = 4) are less prevalent. Increased awareness over time led to a marked ATTR diagnostic surge, steep non-invasive diagnostic approach increment and increased nuclear medicine and external cardiologist referrals (all p < 0.001). A total of 41% (n = 57/139) of patients were referred by non-cardiology specialist disciplines. Specific referral to rule out CA (24–36%) and diagnostic time lag from symptom onset (9 ± 12 to 8 ± 14 months), however, did not improve (all p > 0.050). Multiple early red flag events preceded CA diagnose several years in ATTR: Left ventricular hypertrophy (LVH, 60%, 4.9 ± 4.3 y), heart failure (54%, 2.5 ± 3.5 y), atrial fibrillation (47%, 5.9 ± 6.7 y), bilateral carpal tunnel syndrome (43%, 9.5 ± 5.7 y) and spinal stenosis (40%, 7.4 ± 6.5 y). LVH ≥ 12 mm was absent in 11% ATTR (n = 13/114) and 5% AL (n = 1/21) patients. Hypertension was common in both ATTR (n = 70/114, 62%) and AL (n = 10/21, 48%). 56% (n = 78/139) of CA presented with heart failure. Cumulative 1 and 5-year mortality of 10%/66%, 40%/52% and 75%/75% for ATTR, AL, and AA, respectively, remains high.

Conclusions

Although CA diagnostic uptake and referral improve, specialist-specific disease and diagnostic red flag ignorance result in non-timely diagnosis and unfavourable outcome.

Keywords:

• ATTR amyloidosis
• cardiac amyloidosis
• transthyretin
• outcome
• red flags

Acknowledgements

We are indebted to our research nurse team Kelly De Jaegher, Tineke De Grande and Katrien Derycker for their daily care for our amyloidosis patients and scientific and administrative help. No specific funding related to this study.

Disclosure statement

He is local principal investigator for the ATTRibute-CM and CARDIO-TTRansform amyloidosis trials. No potential conflict of interest was reported by the author(s).

Additional information

Funding

Dr. Debonnaire reports personal fees for speaker activities and company consulting for Pfizer and Alnylam.