Browsing by Author "Pedro, M. M. Mendes"
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- Association of circulating levels of collagen turnover biomarkers with the phenotype in a population with sarcomeric hypertrophic cardiomyopathyPublication . Brito, D. A.; Pedro, M. M. Mendes; Calisto, C.; Pires, R.; Moldovan, O.; Silva, D.; Francisco, A. R.; Guimarães, T.; Pinto, Fausto J.; Madeira, H. C.Background and aim: In patients (pts) with sarcomeric hypertrophic cardiomyopathy (sHCM) and left ventricular hypertrophy (LVH), cardiac fibrosis and diastolic dysfunction are typical features. Studies suggest that collagen turnover (ColT) is increased in sHCM, but its clinical significance and relationship with cardiac LVH and function is doubtful. In order to address this question, we evaluated the association of circulating levels of biomarkers of ColT (bioColT) with clinical, morphological and functional echocardiographic (echo) features. Methods: Thirty nine sHCM pts (49±17y, 54% female) major echo criteria and positive genotype, nondilated left ventricle (LV) and preserved ejection fraction were enrolled, after exclusion of conditions that might influence circulating levels of bioColT. On the same day, clinical evaluation, ECG, echo study and laboratorial tests (including measurement of 6 bioColT related to collagen synthesis and degradation PICP, PIIINP, CITP, MMP1, MMP9 and TIMP) were performed. Associations were looked for between bioColT and: 1) structural and functional parameters and indices of systolic and diastolic function evaluated by echo/tissue Doppler imaging; 2) current NYHA functional class, hospitalization due to sHCM and nonsustained ventricular tachycardia (NSVT) on Holter, during the preceding year. Associations were considered statistically significant if p<0.05. Results: Controlling for age and body mass index, TIMP1 levels (a measure of tissue inhibition of collagentype 1 degradation) correlated with LV mass index (LVMI; r=0.49), septal thickness (ST; r=0.43), maximal wall thickness (MWT; r=0.44), LVWT score (r=0.44), lateral E' (r=−0.49), septal E/E' (r=0.55), and lateral E/E' (r=0.64); and CITP (a measure of collagentype I degradation) levels correlated with LVMI (r=0.38), ST (r=0.36), MWT (r=0.38), LVWT score (r=0.37) and lateral E' (r=−0.45). No correlations were found between PICP or other bioColT levels and echodata. Only TIMP1 levels were significantly increased in the presence of symptoms and hospitalizations (p=0.031). None bioColT was associated with the occurrence of NSVT on Holter. Conclusions: In pts with sHCM and LVH, collagen turnover is active, and acts in favor of a predominance of inhibition of collagen degradation over collagen degradation. Both, TIMP1 and CITP levels were associated with the degree and extension of LVH, but only TIMP1 levels were also positively associated with echoindices of diastolic dysfunction, left ventricular filling pressures and morbidity. Therefore, it appears in this series to be the biomarker of choice amongst ColT biomarkers, for future research.
- Relationship of galectine3 and NTproBNP circulating levels with cardiac hypertrophy and function in patients with sarcomeric hypertrophic cardiomyopathyPublication . Brito, D.; Calisto, C.; Pires, R.; Pedro, M. M. Mendes; Gonçalves, F.; Moldovan, O.; Silva, D.; Guimarães, T.; Francisco, A.R.; Pinto, Fausto J.; Madeira, H. C.Background and aim: Cardiac fibrosis, a hallmark of sarcomeric hypertrophic cardiomyopathy (sHCM) with left ventricular hypertrophy (LVH), is a substrate for ventricular arrhythmias and heart failure. NTproBNP plasma levels in sHCM patients (pts) are associated with LVH, cardiac dysfunction and adverse outcomes. Galectin3 (Gal3), a biomarker of fibrosis, may be also a marker of severity thus reflecting prognosis. We tested this hypothesis evaluating both biomarkers in sHCM pts and their association with clinical, morphological and functional echocardiographic (echo) data. Methods: Sixty sHCM pts (49.8±16.3y, 52% female) – major echo criteria and positive genotype, nondilated well contracting left ventricle (LV), stable clinical condition and no diseases that might influence Gal3 levels – were enrolled. ECG, echo study, and complete laboratorial panel were performed. Associations between circulating Gal3 and NTproBNP levels, and between both biomarkers and imaging data (structural and functional evaluation by echoDoppler/tissue Doppler imaging), current symptoms, hospitalization due to sHCM or presence of nonsustained ventricular tachycardia (NSVT) on Holter, were looked for. Statistical analyses were conducted, first including and then excluding 6 pts under cardiovascular drugs that might influence Gal3 levels. Associations were considered statistically significant if p<0.05. Results: No association was found between Gal3 (14.95±9.29ng/ml) and NTproBNP (1207.02±1779.9 pg/ml) levels or between Gal3 and LVH degree, cardiac dimensions or functional echo parameters or indices, even after adjusting for age and body mass index (BMI). NTproBNP levels were associated with maximal wall thickness (WT), r=0.58), LVWT score (r=0.40), left atrial dimension (r=0.39), septal E' (r=−0.54), lateral E' (r=−0.58), septal E/E' (r=0.49), lateral E/E' (r=0.59), and septal S' (r=−0.58), independently of age and BMI. Higher levels of NTproBNP were found in the presence of symptoms (p<0.001) and hospitalizations due to sHCM (p=.001). None of the biomarkers was associated with NSVT occurrence. Results were similar after the exclusion of pts under potentially confounding therapies. Conclusions: In sHCM pts, NTproBNP but not Gal3 levels are associated with LVH degree, echoindices of LV function, LV diastolic pressure, symptoms and hospitalization. These findings favor NTproBNP but not Gal3 as a helpful tool to identify and characterize sHCM pts at a higher risk for cardiac related morbidity.