Prediction of clinical outcome in patients treated with cardiac resynchronization therapy - the role of NT-ProBNP and a combined response score

BMC Cardiovasc Disord. 2018 Apr 24;18(1):70. doi: 10.1186/s12872-018-0802-8.

Abstract

Background: Cardiac resynchronization therapy (CRT) is an established therapy for appropriately selected patients with heart failure. Response to CRT has been heterogeneously defined using both clinical and echocardiographic measures, with poor correlation between the two.

Methods: The study cohort was comprised of 202 CRT-treated patients and CRT response was defined at 6 months post-implant. Echocardiographic response (E+) was defined as a reduction in LVESV ≥ 15%, clinical response as an improvement of ≥ 1 NYHA class (C+), and biomarker response as a ≥ 25% reduction in NT-proBNP(B+). The association of response measures (E+, B+, C+; response score range 0-3) and clinical endpoints at 3 years was assessed in landmarked Cox models.

Results: Echo and clinical responders demonstrated greater declines in NT-proBNP than non-responders (median [E+/B+]: -52%, [E+]: -27%, [C+]: -39% and [E-/C-]: -13%; p = 0.01 for trend). Biomarker (HR 0.43 [95% CI: 0.22-0.86], p = 0.02) and clinical (HR 0.40 [0.23-0.70] p = 0.001) response were associated with a significantly reduced risk of the primary endpoint. When integrating each response measure into a composite score, each 1 point increase was associated with a 31% decreased risk for a composite endpoint of mortality, LVAD, transplant and HF hospitalization (HR 0.69 [95% CI: 0.50-0.96], p = 0.03), and a 52% decreased risk of all-cause mortality (HR 0.48 [95% CI: 0.26-0.89], p = 0.02).

Conclusion: Serial changes in NT-proBNP are associated with clinical outcomes following CRT implant. Integration of biomarker, clinical, and echocardiographic response may discriminate CRT responders versus non-responders in a clinically meaningful way, and with higher accuracy.

Trial registration: The cohort was combined from study NCT01949246 and the study based on local review board approval 2011/550 in Lund, Sweden.

Keywords: Cardiac response; Cardiac resynchronization therapy; Dilated cardiomyopathy; Heart failure; NT-proBNP.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Boston
  • Cardiac Resynchronization Therapy Devices*
  • Cardiac Resynchronization Therapy* / adverse effects
  • Clinical Decision-Making
  • Decision Support Techniques*
  • Echocardiography
  • Female
  • Heart Failure / blood
  • Heart Failure / diagnostic imaging
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Patient Selection
  • Peptide Fragments / blood*
  • Predictive Value of Tests
  • Prospective Studies
  • Recovery of Function
  • Stroke Volume
  • Sweden
  • Time Factors
  • Treatment Outcome
  • Ventricular Function, Left

Substances

  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain

Associated data

  • ClinicalTrials.gov/NCT01949246