Timing of Dynamic NT-proBNP and hs-cTnT Response to Exercise Challenge in Asymptomatic Children with Moderate Aortic Valve Regurgitation or Moderate Aortic Valve Stenosis

Abstract

Patients with congenital aortic valve stenosis (AVS) can remain asymptomatic but may develop progressive and often underestimated exercise intolerance. The risk of increased left ventricular (LV) wall stress, irreversible myocardial fibrosis and sudden death in untreated patients warrants earlier intervention. The timing for curative therapy for severe AVS is clear, but optimal timing for moderate stenosis (modAS) is unknown. AVS often coexists with aortic regurgitation, which adds a volume overload to an already pressure-overloaded LV, adding an additional challenge to the estimation of disease severity. We investigated the possible value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) upon treadmill exercise challenge in children with asymptomatic modAS versus moderate regurgitation (modAR). The aim was to determine optimal timing of peak biochemical response. Blood samples were obtained at rest, and then at 20, 40 and 60 min after peak exercise comparing modAS and modAR to healthy controls. Exercise performance was equivalent in all groups, with no difference for biomarker levels at rest. The increase in NT-proBNP was significant in modAR at 40 min (99.2 ± 48.6 ng/L; p = 0.04) and 60 min into recovery (100.0 ± 53.7 ng/L; p = 0.01), but not in modAS. The increase in hs-cTnT was significant only at 60 min into recovery for modAS and modAR. NT-proBNP and hs-cTnT following exercise challenge are possible discriminant biomarkers of modAR from modAS and controls at 60 min into recovery despite comparable exercise performance. This offers a promising avenue for future stratification of aortic valve disease and optimal timing of intervention.

Natriuretic Peptide Release during Exercise in Patients with Valvular Heart Disease: a Systematic Review.

“…The resting blood samples were taken after 20-30 minutes after supine rest and the post exercise sample was taken 2-3 minutes after the cessation of exercise. There were only three studies where blood samples were taken at serial intervals post exercise (12)(13)(14).…”

Natriuretic peptide release during exercise in patients with valvular heart disease: A systematic review

“…Highly sensitive troponin, however, was significantly higher at rest in both disease groups and the levels remained similar at 20 and 40 minutes into recovery. 14 The results suggest a novel way to assess valvular heart disease.…”

“…The increase in hs-cTnT was significant only at 60 minutes into recovery for moderate AS and AR. 14 The study looking at CT-ADP and HMWM during exercise showed that these levels did not change significantly between rest and exercise (P = .45 and P = .65, respectively). In 4 out of the 10 subjects, no valid aortic valve velocity could be recorded on exercise; however, in the remaining six patients, CT-ADP during exercise correlated well with aortic valve peak velocity (rho 0.82, P = .04).…”

“…There were only three studies where blood samples were taken at serial intervals post-exercise. [12][13][14] 3 studies described the effect of exercise BNP on cardiovascular outcomes. 10,15,16 Tertiles of exercise BNP were used (Table 2).…”

“…3 out of the 10 study investigators sought to determine the optimal timing of biomarker response, by blood sampling at different timepoints after exercise. [12][13][14] Mawad et al carried out a study to determine the optimal timing of biochemical response of NT pro-BNP and highly sensitive cardiac troponin (hs-cTnT) in children with asymptomatic moderate AS, moderate AR and healthy controls. Following treadmill exercise, NT-proBNP increased significantly at 40 minutes (99.2 ± 48.6 ng/L; P = .04) into recovery and remained elevated at 60 minutes (100.0 ± 53.7 ng/L; P = .01) into recovery, in the AR group.…”