Troponin I levels in permanent atrial fibrillation-impact of rate control and exercise testing

Anja Wiedswang Horjen, Sara Reinvik Ulimoen, Steve Enger, Jon Norseth, Ingebjørg Seljeflot, Harald Arnesen, Arnljot Tveit, Anja Wiedswang Horjen, Sara Reinvik Ulimoen, Steve Enger, Jon Norseth, Ingebjørg Seljeflot, Harald Arnesen, Arnljot Tveit

Abstract

Background: High-sensitivity troponin I (hs-TnI) and troponin T (hs-TnT) are moderately correlated and independently related to outcome in atrial fibrillation (AF). Rate controlling therapy has been shown to reduce hs-TnT, however the potential impact on hs-TnI levels, and whether this differs from the effects on hs-TnT, has not been investigated previously.

Methods: Sixty patients with stable, permanent AF without heart failure or known ischemic heart disease were included in a randomised crossover study (mean age 71 ± 9 years, 18 women). Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered once daily for three weeks, in a randomised sequence. At baseline and on the last day of each treatment period, hs-TnI was measured at rest and after a maximal exercise test and compared to hs-TnT.

Results: Hs-TnI and hs-TnT correlated moderately at baseline (rs = 0.582, p < 0.001). All drugs reduced both the resting and the peak exercise levels of hs-TnI compared with baseline (p < 0.001 for all). The decline in resting hs-TnI and hs-TnT values relative to baseline levels was similar for all drugs except for verapamil, which reduced hs-TnI more than hs-TnT (p = 0.017). Levels of hs-TnI increased significantly in response to exercise testing at baseline and at all treatment regimens (p < 0.001 for all). The relative exercise-induced increase in hs-TnI was significantly larger compared to hs-TnT at baseline (p < 0.001), on diltiazem (p < 0.001) and on verapamil (p = 0.001).

Conclusions: In our population of stable, permanent AF patients, all four rate control drug regimens reduced hs-TnI significantly, both at rest and during exercise. The decline in hs-TnI and hs-TnT levels associated with beta-blocker and calcium channel blocker treatment was similar, except for a larger relative decrease in hs-TnI levels following verapamil treatment.

Trial registration: www.clinicaltrials.gov ( NCT00313157 ).

Keywords: Atrial fibrillation; Biomarkers; Exercise testing; High-sensitivity cardiac troponin I; High-sensitivity cardiac troponin T; Rate control.

Figures

Fig. 1
Fig. 1
Flow chart of the study. HR, heart rate; n, number of patients; SR, sinus rhythm
Fig. 2
Fig. 2
Resting hs-TnI levels at baseline and during treatments. All drug regimens reduced the resting levels of high-sensitivity troponin I compared to baseline (p < 0.001 for all, p-values derived from the Wilcoxon signed-rank test). Center lines show the medians; box limits indicate the 25th and 75th percentiles; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Abbreviations: hs-TnI, high-sensitivity troponin I
Fig. 3
Fig. 3
Relative decrease in hs-TnI and hs-TnT levels following treatment. The decline in hs-TnI and hs-TnT levels associated with beta-blocker and calcium channel blocker treatment was similar, except for a larger relative decrease in hs-TnI levels following verapamil treatment (p = 0.017) (p-values derived from the Mann–Whitney U-test). Center lines show the medians; box limits indicate the 25th and 75th percentiles; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Abbreviations: hs-TnI, high-sensitivity troponin I; hs-TnT, high-sensitivity troponin T
Fig. 4
Fig. 4
Relative exercise-induced increase in hs-TnI and hs-TnT levels. The relative exercise-induced increase in hs-TnI was significantly larger compared to hs-TnT at baseline (p < 0.001) and at treatment with diltiazem (p < 0.001) and verapamil (p = 0.001) (p-values derived from the Mann–Whitney U-test). Center lines show the medians; box limits indicate the 25th and 75th percentiles; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles. Abbreviations: hs-TnI, high-sensitivity troponin I; hs-TnT, high-sensitivity troponin T
Fig. 5
Fig. 5
Scatterplot showing the association between baseline levels of logarithmically transformed hs-TnI and hs-TnT. Scatterplot with fitted linear regression line and 95 % confidence interval curves. Regression coefficient was 0.35, 95 % CI (0.28, 0.42), p < 0.001, adjusted R2 0.24. Abbreviations: hs-TnI, high-sensitivity troponin I; hs-TnT, high-sensitivity troponin T

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