Galectin-3 and sST2: associations to the echocardiographic markers of the myocardial mechanics in systemic sclerosis - a pilot study.

BACKGROUND: Progressive cardiac fibrosis is the central aspect of the myocardial involvement in systemic sclerosis (SSc). We hypothesized that circulating biomarkers of the cardiac fibrosis may be useful in the early diagnosis of the cardiac manifestation in this disease. Thus, we investigated the potential correlations between the levels of galectin-3, soluble suppression of tumorigenicity-2 (sST2) and the echocardiographic markers of the myocardial mechanics in SSc patients. METHODS: Forty patients (57.3 ± 13.7 years, 36 female) were investigated. In addition to the conventional echocardiography, tissue Doppler and speckle tracking-derived strain techniques were used to assess the function of both ventricles and atria. To estimate the correlations between galectin-3 and sST2 levels and the echocardiographic variables, partial correlation method was used with age as correcting factor. RESULTS: In age adjusted analysis galectin-3 level showed significant correlation with left ventricular global longitudinal strain (r = 0.460, p = 0.005); grade of left ventricular diastolic dysfunction (r = 0.394, p = 0.013); septal e' (r = - 0.369, p = 0.021); septal E/e' (r = 0.380, p = 0.017) and with the grade of mitral regurgitation (r = 0.323, p = 0.048). No significant correlation was found between sST2 levels and the echocardiographic variables. CONCLUSIONS: Galectin-3 levels, but not sST2 levels show significant correlation with the parameters of the left ventricular systolic and diastolic function. Galectin-3 may be a useful biomarker for the screening and early diagnosis of SSc patients with cardiac involvement.

Impairment of Left Atrial Mechanics Is an Early Sign of Myocardial Involvement in Systemic Sclerosis.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is common in systemic sclerosis (SSc). Less is known, however, about left atrial (LA) mechanics in this context. The aim of this study was to investigate the correlation between LV diastolic function and LA mechanics in SSc patients with the use of volumetric and 2-dimensional speckle tracking-derived strain techniques and to compare the results with those obtained in healthy subjects. METHODS AND RESULTS: Seventy-two SSc patients and 30 healthy volunteers (H) were investigated. LV diastolic function was classified as normal (I), impaired relaxation (II), and pseudonormal pattern (III). LA reservoir (H: 51.8 ± 7.4%; I: 45.1 ± 8.1%; II: 42.2 ± 6.6%; III: 36.6 ± 7.3%; analysis of variance: P < .001) and contractile strain (H: 24.8 ± 4.9%; I: 18.2 ± 4.4%; II: 21.5 ± 2.8%; III: 16.8 ± 3.6%; P < .001) already showed significant worsening in SSc patients with preserved LV diastolic function compared with healthy subjects. LA conduit strain (H: 27.1 ± 4.6%; I: 26.9 ± 5.7%; II: 20.6 ± 6.1%; III: 19.5 ± 5.3%; P < .001) was preserved in this early phase. Further deterioration of reservoir strain was pronounced in the pseudonormal group only. LA contractile strain increased significantly in the impaired relaxation group and then decreased with the further worsening of the LV diastolic function. Regarding phasic volume indices, the differences between groups were not always statistically significant. CONCLUSION: LA mechanics strongly reflects the changes in LV diastolic function in SSc. On the other hand, strain parameters of the LA reservoir and contractile function already show significant worsening in SSc patients with preserved LV diastolic function, suggesting that impairment of the LA mechanics is an early sign of myocardial involvement in SSc.

Left atrial stiffness is superior to volume and strain parameters in predicting elevated NT-proBNP levels in systemic sclerosis patients.

Heart failure with preserved ejection fraction (HFpEF) is common in systemic sclerosis (SSc) and implies a worse prognosis therefore non-invasive assessment of left ventricular (LV) filling pressure is pivotal. Besides E/e' the use of maximal left atrial volume (LA Vmax index) is recommended. LA reservoir strain was also reported to be useful. The utility of LA stiffness, however, was never investigated in SSc. Thus we aimed to compare the diagnostic power of LA Vmax index, reservoir strain and stiffness in predicting elevated LV filling pressure in SSc patients. 72 SSc patients (age: 57 ± 11 years) were investigated. LA stiffness was calculated as ratio of E/e' to LA reservoir strain. Elevated LV filling pressure was defined as NT-proBNP > 220 pg/ml. Receiver-operating characteristic (ROC) curves were used to estimate the diagnostic performance of the investigated parameters. Average NT-proBNP level was 181 ± 154 pg/ml. NT-proBNP > 220 pg/ml was found in 21 SSc patients. LA stiffness showed the highest diagnostic performance in predicting NT-pro-BNP > 220 pg/ml, with a cut off value of 0.314 (Area under the curve: 0.719, specificity: 89.4%, sensitivity: 42.1%). AUC values for LA reservoir strain and Vmax index were 0.595 and 0.521, respectively. LA stiffness was superior to Vmax index and reservoir strain in predicting elevated NT-proBNP levels in SSc patients. Although invasive validation studies on larger samples are required, our data suggest, that the use of LA stiffness may significantly contribute to diagnostic precision in populations with a high suspicion of HFpEF.

Relation of Right Atrial Mechanics to Functional Capacity in Patients With Systemic Sclerosis.

Cardiac involvement in systemic sclerosis (SSc) implies a worse prognosis. Little is known about the right atrial (RA) mechanics in this disease, but recent data suggest that it correlates well with the functional capacity of the patients in conditions with known right heart involvement. Thus we aimed to investigate the abnormalities of the RA function as compared with healthy subjects and to assess the potential correlations between RA mechanics and the functional capacity in SSc patients using 2D speckle tracking technique. A total of 70 SSc patients (age: 57 ± 12 years) were investigated. Functional capacity was measured with 6-minute walk test (6MWT). Echocardiographic parameters of the right ventricular (RV) systolic function (TAPSE, RVFAC), parameters of the tricuspid inflow (E, A), and tricuspid annular systolic (S), early- (e') and late- (a') diastolic myocardial velocities were measured. RV wall thickness was obtained. RA reservoir (εR), conduit (εCD), and contractile (εCT) strain were measured. RA stiffness was calculated as ratio of E/e' to εR. Echocardiographic data were compared with an age- and gender-matched group of 25 healthy volunteers. RA εR (49.3 ± 10.7 vs 59.6 ± 9.9%, p = 0.000) and εCD (26.8 ± 8.1 vs 34.3 ± 7.3%, p = 0.000) were significantly lower in SSc patients. No significant difference was found in εCT (22.9 ± 5.8 vs 25.3 ± 5.7%, p = 0.082). RA stiffness was significantly increased in SSc patients (0.11 ± 0.04 vs 0.08 ± 0.02, p = 0.001). 6MWT distance was 391 ± 95m. In stepwise multiple linear regression analysis RV wall thickness (r = -0.289, p = 0.030) and RA stiffness (r = -0.418, p = 0.002) became independent predictors of 6MWT distance. In conclusion, RA εR and εCD are impaired, while RA stiffness is increased in SSc compared with healthy subjects. Speckle tracking-derived RA stiffness is turned out to be one of the main determinants of the functional capacity in SSc patients.