Patient trajectories and disease progression in transthyretin amyloid cardiomyopathy: insights from the HANSE ATTR-TRACK real-world registry

Background

Recent randomized controlled trials have provided robust evidence for disease-modifying therapies in transthyretin amyloid cardiomyopathy (ATTR-CM). However, systematic longitudinal follow-up data from real-world registries remain limited.

Methods

Between January 1, 2020, and December 31, 2024, all patients referred for suspected ATTR-CM within the Heart Failure (HF) Network were consecutively included. (1) Clinical, functional, and laboratory parameters were assessed according to current expert consensus criteria for ATTR-CM disease progression (DP). (2) Baseline (BL) and follow up (FU) characteristics were compared between patients with and without DP (+ positiv, - negativ). Outcomes of first (2020–2022) vs. latest referrals (2023–2024) were evaluated for increasing disease awareness.

Results

Overall, 80 patients were referred for diagnostic evaluation with confirmation of 46 ATTR-CM patients (44 wildtype, 2 variant). The annual number of cases increased steadily over time (2020: n=3; 2021: n=6; 2022: n=8; 2023: n=8; 2024: n=21). Five patients did not receive disease-modifying therapy due to advanced HF (n=3) and frailty (n=2). The remaining 41 patients were treated with tafamidis and followed for a median of 793±546 days. Mean age was 78.1±7.5 years, and 90% were male. At BL, concomitant polyneuropathy was present in 45.6% and autonomic dysfunction in 30.4%. All patients had HF (NYHA I: 2.4%; NYHA II: 75.6%; NYHA III: 22.0%), with high prevalence of arterial hypertension (83%) and chronic kidney disease (66%).

DP occurred in 6 patients (DP+, 14.6%), while 35 patients (DP-, 85.4%) showed no progression or only one criterion indicating sustained disease stabilization with long-term therapy. FU NT-proBNP levels (DP- 3,256±3,848 vs. DP+ 12,446±8,432 pg/mL, p<0.001), mortality (DP- 11.4% vs. DP+ 66.6%, p<0.001), and cardiovascular rehospitalizations (DP- 42.9% vs. DP+ 83.3%, p=0.022) were significantly lower in patients without DP.

Patients from 2023–2024 benefited from earlier treatment initiation (Latest 42.1±83.2 vs. First 77.1±235.7 days, p=0.01) better functional status (Latest NYHA class 2.1±0.4 vs. First 2.4±0.5, p=0.04) and lower mortality (Latest 8% vs. First 38%, p=0.02) despite comparable BL NT-proBNP levels and left ventricular ejection fraction.

Among untreated patients, all individuals with progressive HF showed worsening NT-proBNP, renal function decline, intensification of diuretic therapy, and ultimately died during FU (mean time to death: 414.0 days). One ATTRv-CM patient required therapeutic escalation from tafamidis to vutrisiran due to progressive polyneuropathy, while cardiac status remained stable over five years of FU.

Conclusion

In this real-world registry, most ATTR-CM patients demonstrated sustained disease stabilization and favorable clinical trajectories under treatment. HF networks were associated with earlier diagnosis and treatment initiation with improved outcomes.