Research Summary

Early NT-proBNP Worsening, Heart Failure Hospitalization Predict Mortality at 6 Months in ATTR-CM

Anthony Calabro, MA

Key Highlights

  • This landmark survival analysis evaluated whether established 12-month ATTR-CM progression markers had prognostic value when assessed at 6 months.
  • Among 596 consecutive patients with ATTR-CM, 586 patients (98.3%) were alive at 6 months.
  • In a multivariable Cox regression, worsening NT-proBNP and heart failure hospitalization were the only progression markers independently associated with mortality at 6 months.
  • The findings suggest these 2 markers may serve as early indicators of disease progression in ATTR-CM.

Worsening NT-proBNP levels and hospitalization for heart failure at 6 months were independent predictors of mortality among patients with transthyretin amyloid cardiomyopathy (ATTR-CM), according to findings published in the European Journal of Preventive Cardiology.

ATTR-CM is a serious, progressive disease, and several progression markers have previously demonstrated prognostic value at 12 months. However, the study authors noted that the usefulness of these markers for early identification of patients with an unfavorable disease course remains uncertain.

Researchers conducted a landmark survival analysis of 596 consecutive patients with ATTR-CM. The analysis evaluated 5 established 12-month ATTR-CM progression markers assessed at 6 months from baseline: outpatient loop diuretic dose intensification, worsening NT-proBNP, worsening New York Heart Association (NYHA) functional class, worsening estimated glomerular filtration rate, and hospitalization for heart failure within the first 6 months.

Outpatient loop diuretic dose intensification was defined as any increase in loop diuretic dose. Worsening NT-proBNP was defined as an increase of more than 30% and more than 700 pg/mL, and worsening estimated glomerular filtration rate was defined as a reduction of more than 20%. For each marker, researchers included only patients with available 6-month data and follow-up information.

Study Findings

At 6 months, 586 of 596 patients (98.3%) were alive. Among patients with available data, 189 of 532 patients (35.5%) met the criterion for outpatient loop diuretic dose intensification, 114 of 427 patients (26.7%) met the criterion for worsening NT-proBNP, and 56 of 456 patients (12.3%) met the criterion for worsening estimated glomerular filtration rate.

In addition, 70 of 525 patients (13.3%) had worsening NYHA functional class, and 47 of 586 patients (8%) were hospitalized for heart failure within the first 6 months.

A Kaplan-Meier analysis showed that outpatient loop diuretic dose intensification (P = .018), worsening NT-proBNP (P < .001), heart failure hospitalization (P = .012), and worsening estimated glomerular filtration rate (P = .019) were associated with mortality during follow-up. Worsening NYHA functional class was not reported as associated with mortality in this analysis.

In a Cox analysis, outpatient loop diuretic dose intensification was associated with higher mortality during follow-up (hazard ratio [HR], 1.48; 95% CI, 1.06-2.05; P = .02), as was worsening NT-proBNP (HR, 2.66; 95% CI, 1.80-3.93; P < .001), worsening estimated glomerular filtration rate (HR, 1.74; 95% CI, 1.09-2.78; P = .02), and heart failure hospitalization (HR, 4.07; 95% CI, 2.73-6.07; P < .001).

When the 4 criteria associated with mortality were jointly evaluated with other prognostic variables, including National Amyloid Centre stage and age, only worsening NT-proBNP (HR, 1.91; 95% CI, 1.29-2.84; P = .01) and heart failure hospitalization (HR, 1.98; 95% CI, 1.11-3.52; P = .02) remained independently associated with mortality at 6 months.

Clinical Implications

According to the study authors, assessing 12-month ATTR-CM prognostic markers at 6 months showed that worsening NT-proBNP levels and heart failure hospitalization may help identify patients with ATTR-CM who are experiencing early disease progression.

Expert Commentary

“The evaluation of 12-month prognostic markers in ATTR demonstrated that worsening of NT-proBNP levels and HF hospitalization at 6 months are independent predictors of mortality in patients with ATTR and may serve as early indicators of disease progression,” the researchers concluded.

Reference
De Castro D, Brandão M, Peiró-Aventín B, et al. Early markers of diasease progression in ATTR-CM free. Eur J Prev Cardiol. 2026;33(Suppl 1).002. doi:10.1093/eurjpc/zwag115.002