MR-proADM Predicts Mortality and Heart Failure Events in ATTR Cardiac Amyloidosis

31 Mar 20264 min read0 viewsJournal Feed

GIST

Circulation, Ahead of Print. BACKGROUND:With the increasing diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) at earlier stages and new therapies, there is a rising demand for tools to stratify risk and prognosis.

We evaluated the prognostic value of multiple circulating biomarkers for predicting outcomes in ATTR-CM.METHODS:We evaluated 12 different circulating biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI], mid-regional pro-adrenomedullin [MR-proADM], carbohydrate antigen 125 [CA125], soluble suppressor of tumorigenicity 2 [sST2], cluster of differentiation antigen 146 [CD146], growth/differentiation factor-15 [GDF-15], alpha-klotho, fibroblast growth factor 23 [FGF-23], galectin-3, insulin-like growth factor-binding protein 7 [IGFBP-7], and estimated glomerular filtration rate [eGFR]) in 337 ATTR-CM patients from Spain. Cox models were employed to determine their predictive abilities.

Findings were validated in 2 independent external cohorts of 210 patients from the United States and 416 patients from the ATTR-ACT trial, respectively.RESULTS:Over a median follow-up of 19.7 months (IQR, 6.5–42.3), 67 patients (19.9%) died/underwent heart transplantation, and 81 (24%) had heart failure events.

Clinical Editorial

Study design and scope

Outcomes included death or heart transplantation (n=67) and heart failure events (n=81).

Researchers assessed 12 circulating biomarkers in 337 patients with transthyretin amyloid cardiomyopathy (ATTR-CM) from Spain to gauge their ability to predict outcomes.
Cox regression models were used to evaluate predictive performance.
Findings were validated in two external cohorts: 210 US patients and 416 from the ATTR-ACT trial.
Follow-up median was 19.7 months (IQR 6.5–42.3).

Major signal: MR-proADM as strongest predictor

Mid-regional pro-adrenomedullin (MR-proADM) emerged as the biomarker with the strongest prognostic signal for all-cause mortality (C-index 0.788; 95% CI 0.723–0.851) and for the composite of death or heart failure events (C-index 0.721; 95% CI 0.669–0.772).
MR-proADM correlated with multiple measures of ATTR-CM severity and independently predicted mortality, heart failure events, and the composite outcome.

Thresholds and incremental value

An MR-proADM level of ≥1.1 nmol/L was identified as the optimal prognostic threshold.
Adding MR-proADM ≥1.1 nmol/L to established staging systems improved predictive performance:
National Amyloid Center: AUC improved from 0.682 to 0.737 (P<0.001)
Mayo staging: AUC improved from 0.659 to 0.749 (P<0.001)
Columbia staging: AUC improved from 0.699 to 0.768 (P<0.001)
The adverse association with outcomes for MR-proADM ≥1.1 nmol/L was confirmed across both external validation cohorts (P<0.001) and also in patients treated with tafamidis.

Context and implications

MR-proADM levels tracked with disease severity and were independently linked to mortality and heart failure events in ATTR-CM.
Across internal and external cohorts, elevated MR-proADM identified higher-risk patients, including those receiving a targeted disease-modifying therapy (tafamidis).

Limitations and caveats

The summary relies on reported associations and statistical thresholds; no causal inferences or treatment guidance are provided.
Although validated in independent cohorts, the practical integration into routine risk stratification would require prospective assessment and consideration of assay availability.

Bottom line

MR-proADM stands out among evaluated biomarkers as a robust prognostic indicator in ATTR-CM, with higher levels (≥1.1 nmol/L) signaling greater risk for mortality and heart failure–related events and offering incremental prognostic value beyond established staging systems.