High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis

Abstract

Aims: High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome.

Methods and results: Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm(2)) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact of REgression (SALTIRE) study, had long-term follow-up for the occurrence of aortic valve replacement (AVR) and cardiovascular deaths. Over a median follow-up of 10.6 years (1178 patient-years), 24 patients died from a cardiovascular cause and 60 patients had an AVR. Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 (95% CI, 1.22 to 2.55) independent of age, sex, systolic ejection fraction, and aortic stenosis severity.

Conclusions: In patients with aortic stenosis, plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death.

Keywords: Aortic stenosis; Cardiac magnetic resonance; High-sensitivity troponin; Left ventricular hypertrophy; Myocardial fibrosis.

Figure 1

Comparison of two patients with severe aortic stenosis. Both had similar severity of aortic valve narrowing (peak aortic jet velocity in Patient A was 4.8 m/s and Patient B 5.1 m/s) and neither had significant coronary artery disease. However, the high-sensitivity troponin I concentration was more than four-fold higher in Patient A (11.9 ng/L) compared with Patient B (2.5 ng/L), consistent with the more advanced hypertrophic response observed in this patient (left ventricular mass index in Patient A was 114 g/m² and Patient B was 81 g/m²). Furthermore, Patient A had evidence of focal mid-wall fibrosis on late gadolinium imaging (LGE) and myocardial T1 mapping (Patient B did not) and more extensive collagen staining with picrosirius red staining on myocardial biopsy.

Figure 2

Correlation between indexed left ventricular mass and plasma cardiac troponin I concentrations (log-transformed). Similar correlation was seen in patients with (A) and without (B) coronary artery disease.

Figure 3

Patients with aortic stenosis and mid-wall late gadolinium enhancement (LGE) had a two-fold increase in cardiac troponin I concentrations compared with those without LGE and age- and sex-matched healthy patients.

Figure 4

Ten-year event-free survival for composite endpoint of aortic valve replacement or cardiovascular death by tertiles of cardiac troponin I concentrations. Patients in the highest tertile were associated with lower survival rates compared with patients in the other tertiles (log rank test for trend, P = 0.016).