| Part One:Significance and Determinants of Cardiac Troponin I in Patients with Obstructive Hypertrophic CardiomyopathyObjectives:Serum cardiac troponins have been demonstrated to have important clinical implications in patients with hypertrophic cardiomyopathy (HCM). However, little is known about their roles in patients with obstructive HCM. The aim of this study was to explore the clinical significance and determinants of serum cardiac troponin I (cTnI) in patients with obstructive HCM using cardiovascular magnetic resonance imaging.Methods:We investigated the relations between serum cTnI levels and clinical, echocardiographic, and cardiovascular magnetic resonance parameters and assessed the determinants of serum cTnI in 149 consecutive patients with obstructive HCM.Results:The median level of serum cTnI was 0.019 ng/ml (interquartile range 0.009 to 0.044). CTnI was elevated (≥0.04 ng/ml) in 42 (28%) of the overall cohort. Patients with elevated cTnI had greater maximum wall thickness (P <0.001), larger left ventricular mass index (LVMI, P<0.001), more frequency of left atrium diameter≥50 mm (P = 0.020), higher plasma values of N-terminal pro-B-type natriuretic peptide (P<0.001), and less hypertension (P = 0.014). Serum cTnl levels were positively correlated with maximum wall thickness (r = 0.444, P<0.001), LVMI (r = 0.556, P <0.001), N-terminal pro-B-type natriuretic peptide (r= 0.305, P <0.001), left ventricular end-diastolic volume index (r = 0.246, P = 0.002), and left ventricular end-systolic volume index (r = 0.272, P = 0.001), but negatively with left ventricular ejection fraction (r = -0.180, P = 0.028). On multivariate analysis, LVMI was independently associated with both elevated cTnl (odds ratio 1.032, P = 0.001) and increasing serum cTnI levels (β= 0.556, P <0.001). In addition, the presence of hypertension was independently related to less likely elevated cTnI (odds ratio 0.307, P = 0.029) and decreasing levels of serum cTnI (β= -0.165, P = 0.015).Conclusions:Serum cTnI are elevated in a significant proportion of our patients. Serum cTnl is associated with multiple parameters of disease severity, suggesting its great significance in assessing cardiac remodeling in patients with obstructive HCM. Left ventricular hypertrophy, as indicated by LVMI, is the major determinant of serum cTnl levels.Part Two:Predictive Values of N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin I for Myocardial Fibrosis in Obstructive Hypertrophic CardiomyopathyObjectives:Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), in patients with non-obstructive hypertrophic cardiomyopathy (HCM). However, their values to predict myocardial fibrosis in obstructive HCM remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and cardiac troponin I (cTnl) to identify LGE-CMR in patients with obstructive HCM.Methods:Peripheral concentrations of NT-proBNP and cTnI were determined in patients with obstructive HCM (n= 163; age= 47.2 ± 10.8 years; 38.7% females). Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis.Results:LGE was detected in 120 of 163 patients (73.6%). Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6-2340.8] vs.866.6 [707.2-1875.2] pmol/L, P= 0.003; 0.024 [0.010-0.049] vs. 0.010 [0.005-0.021] ng/ml, P<0.001, respectively). The extent of LGE was positively correlated with log cTnI (r= 0.371, P <0.001) and log NT-proBNP (r= 0.211, P= 0.007). On multivariable analysis, both log cTnI and maximum wall thickness (MWT) were independent predictors of the presence of LGE (OR= 3.193, P= 0.033; OR= 1.410, P< 0.001, respectively), whereas log NT-proBNP was not. According to the ROC curve analysis, combined measurements of MWT≥21 mm and/or cTnI≥0.025ng/ml indicated good diagnostic performance for the presence of LGE, with specificity of 95% or sensitivity of 88%.Conclusions:Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with obstructive HCM.Part Three:Gender-related Differences in the Association between Serum Uric Acid and Left Ventricular Mass Index in Patients with Obstructive Hypertrophic CardiomyopathyObjectives:Serum uric acid (SUA) is associated with left ventricular hypertrophy in a wide spectrum of study population. However, whether this association exists in patients with hypertrophic cardiomyopathy (HCM, including obstructive HCM), and if present, whether gender has any impact on this association, remains unknown.Methods:A total of 161 patients with obstructive HCM (age 47.2 ± 10.8 years,99 [62%] men) were included in this study. All patients underwent extensive clinical, laboratory, echocardiographic and cardiac magnetic resonance (CMR) imaging examinations. Left ventricular mass index (LVMI) was assessed using CMR.Results:The mean value of SUA was 353.4 ± 87.5 μmol/L. Both SUA levels (381.2 ± 86.4 vs.309.0 ± 69.3μmol/L, p <0.001) and LVMI (96.2 ± 32.1 vs.84.4 ± 32.4 g/m2, p= 0.025) were significantly higher in men than in women. LVMI increased progressively across sex-specific tertiles of SUA in women (p = 0.030), but not in men (p = 0.177). SUA was positively correlated with LVMI in female patients (r = 0.372, p = 0.003), but not in males (r = 0.112, p = 0.269). On multivariate linear regression analysis, SUA was independently associated with LVMI in females (p = 0.375, p = 0.002), but not in males.Conclusions:SUA levels are significantly and independently associated with LVMI in women with obstructive HCM, but not in men. Our findings imply the potential significance of urate-lowering regimens in female patients with obstructive HCM. |
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