ABC | Volume 114, Nº4, April 2020

Original Article Fernandes et al. Galectin-3 in pericardial constriction Arq Bras Cardiol. 2020; 114(4):683-689 Table 3 – Effect of pericardiectomy on functional capacity Variables Pre Post p Velocity (mph) 2.5 [2-2.5] 3 [2.5-3.3] 0.001 Exercise time (min) 9.5 [6.9-11.7] 9.9 [4.5-14] 0.397 Peak HR (bpm) 139 [114-160] 159 [138-178] 0.020 VO 2 at AT (mL/kg/min) 13.5 [11.2-14.6] 16.4 [13.8-20.75] 0.002 AT (%)* 73 [60-81] 69.5 [62.5-78.5] 0.856 peak VO 2 (mL/kg/min) 18.5 [14.6-22.9] 25.4 [22.3-28.6] < 0.001 peak VO 2 (%)* 63 [49.5-70.5] 82 [69.5-95] < 0.001 Peak V E (L/min) 48 [41.3-57.6] 61.7 [44.5-79.9] < 0.001 V E /VCO 2 slope RER 35.5 [30-40] 1.1 29 [28-31.5] 1.1 < 0.001 > 0.05 * Percentage in relation to predicted for age and sex. Continuous variables are presented as median and interquartile range [IQR], categorical data are presented as percentage. VO 2 : oxygen consumption;AT: anaerobic threshold; HR: heart rate; VO 2 : oxygen consumption; VE: pulmonary ventilation; RER: respiratory exchange ratio. points of the study. Overall, after surgical intervention, patients experienced improvement in cardiopulmonary capacity (Table 3) in treadmill speed, peak heart rate, peak oxygen consumption (peak VO 2 ) at anaerobic threshold (AT), AT, VO 2 and V E /VCO 2 slope. BNP values had no correlation with CPET parameters either before or after the pericardiectomy procedure. However, although the Gal-3 marker did not correlate with CPET parameters before the procedure, we observed a moderate inverse correlation with test duration (r = –0.79; p < 0.001), exercise time (r = –0.79; p < 0.001), and heart rate at AT (r = 0.60; p = 0.01) in the postoperative period. Histopathological study Histological study was performed of 21 samples. Severe fibrosis and calcification were a common finding, observed in 19 (90.5%) and 12 (57.1%) of the specimens, respectively. Histopathological examination revealed mild inflammation in 16 cases (76.2%). No statistically significant association was found between Gal-3 and these findings (Table 4). Discussion Our study showed that patients diagnosed with CCP had normal levels of Gal-3 preoperatively, comparable with the control group. Also, we observed no significant correlation of Gal-3 with echocardiographic and CMR measures and BNP. After pericardiectomy, we observed an improvement in peak VO 2 and V E /VCO 2 slope, which are makers of poor prognostic. However, we observed negative associations between Gal‑3 and CPET parameters after pericardiectomy, such as test duration and exercise time. Gal-3 has long been known to be a mediator of fibrosis in multiple organs, including the heart, kidney, pancreas, liver, and lung. 8 Nevertheless, no studies have been performed on clinical data of CCP patients, associating levels of Gal-3 with pericardial structure, function, and functional status. Ntsekhe et al. 5 studied AcSDKP and galectin levels in normal pericardial fluid and tuberculous pericardial effusion. 5 AcSDKP exerts part of its antifibrotic effect by inhibiting Gal-3, which is inactivated by angiotensin-converting enzyme (ACE). The authors concluded that depressed levels of AcSDKP in conjunction with normal or low Gal-3 levels within the pericardium may explain the high incidence of constrictive pericarditis associated with tuberculous pericarditis. Constrictive pericarditis is a heterogeneous disorder and the risk of constriction after an acute episode is correlated with the etiology. Imazio et al. 9 found a incidence of constrictive pericarditis < 0.5% in idiopathic or viral acute pericarditis; 2.8% for connective tissue disease, 4.0% for neoplastic pericarditis; 20% for tuberculous pericarditis, and 33% for purulent pericarditis. In our cohort, most patients (76%) had an idiopathic etiology, and we cannot extrapolate our results to other etiologies. Only a study with more patients and different etiologies may elucidate whether galectin can modulate constriction. Inflammation is a physiological process that acts as a trigger for fibrosis and tissue regeneration following injury. The pericardium is a poorly vascularized structure with fibers composed of collagen that generally do not show the delayed enhancement observed with gadolinium injection. In cases where there is hyperemia and inflammation in the pericardium, there is increased vascularization resulting in an increase in late pericardial enhancement on CMR. 10 Zurik et al. 2 also observed that pericardial delayed hyperenhancement on CMR is common in patients with CCP and is associated with histological markers of chronic inflammation and increased neovascularization, which is indicative of an ongoing, dynamic active inflammatory reaction. 2 Patients with CCP without pericardial delayed hyperenhancement had more pericardial fibrosis and calcification and a less pericardial thickening. We also did not observe any significant association of Gal-3 levels with pericardial thickness and pericardial late enhancement evaluated by CMR. One explanation as to why some patients with CCP do not improve after surgery is myocardial atrophy after prolonged constriction, residual constriction, or a concomitant myocardial process that leads to prolonged cardiac failure in spite of successful pericardiectomy. 11,12 Another possibility is myocardial fibrosis. Probably, the Gal-3-induced fibrosis is restricted to the myocardium and not the pericardium. We also did not 687