IJCS | Volume 31, Nº2, March / April 2018

178 commonly mild in the advanced stages of the disease, compared to the more exuberant systemic congestion, and the pulmonary semiology may be more affected by the signs of pleural effusion than by crepitations, as well as by lower systemic pressure levels in this group of patients. The progression to acute pulmonary edema in these cases is even more rare. 20 These particularities in the clinical presentation may relate to the most frequent concomitance of biventricular dysfunction, with right ventricular heart failure, sometimes earlier and more pronounced than the left one in T. cruzi infected patients. Thromboembolic manifestations Pulmonary and systemic embolisms are common manifestations in patients with CCC, as a result of murine thrombosis from cardiac chambers and systemic vein thrombosis, and are a major cause of embolic stroke and other morbidities. Thromboembolic accidents are often the first manifestation of the disease and may occur in stages without ventricular dysfunction (Stage B2). However, as in several other cardiopathies, cavity dilation and HF syndrome are known associated risk factors. Nevertheless, it is chronic regional ventricular dyskinesia, mainly apical, such as the classic aneurysm of the glove finger, which has shown a special propensity for the formation of mural thrombi and the consequent embolic events, particularly the systemic ones. As predicted, atrial fibrillation, even when present in the minority of this population, as a relatively late and secondary manifestation to the ventricular dysfunction, also constitutes an additional thrombogenic factor. Pulmonary embolization, which can originate from peripheral venous thrombi and right cardiac cavities, is much less frequently clinically diagnosed, but its incidence is certainly underestimated, compared to its prevalence in necropsy material. 29 There is a clear lack of data to provide an estimate of the actual incidence of clinical thromboembolism in CCC, but series of autopsies and clinical studies indicate high rates of intracardiac thrombi and thromboembolic events in this population. In a revision of 1345 necropsies of patients with chronic chagasic cardiomiopathy, thromboemboli and/or intracardiac thrombi were observed in 44% of cases. 29 Thrombi were equally frequent in right and left cardiac cavities. Systemic circulation thromboembolism was more frequent, but more associated with fatal events. Atransthoracic and transesophageal echocardiography study showed that thromboembolism frequently originated from the heart in 75 T. cruzi chronically infected patients without symptoms of heart failure, or with mild symptoms. Left ventricular mural thrombi were found in 23% of patients and were associated with previous history of stroke. Apical aneurysm was identified in 47% of patients and was significantly related to mural thrombosis and the occurrence of stroke. Left and right atrial appendage thrombosis was present in 4 and 1 patient, respectively. During the 24-month follow-up period, 1 non-fatal stroke event and 13 deaths were observed, 7 of which were sudden, 5 due to HF progression and 1 death by stroke. 30,31 Systematic revision of 8 observational studies, involving 4158 patients, addressed the association between CCC and the risk of stroke. 32 The results indicate that chronically T. cruzi infected patients, when compared to the non-infected, had an excess risk of stroke of about 70% (RR = 1.70; HF 95%: 1.06 to 2.71). When the analysis was limited to 3 studies, with more strict criteria for stroke, an even higher excess risk was found (RR = 6.02; HF 95%: 1.86 to 19.49). The characteristics of stroke patients with CCC were explored in a study of 94 patients with acute ischemic stroke, comparedwith the characteristics of a control group of patients without CCC. T. cruzi infected individuals showed higher rates of cardioembolic stroke (56% versus 9%), left ventricular dilatation (23%versus 5%), LVmural thrombosis (12%versus 2%), apical aneurysm (37%versus 1%) and atrial fibrillation (14% versus 5%). 23 Prevention of cardioembolic stroke in patients with CCC The I Latin American Guideline for the Diagnosis and Treatment of Chagas Cardiopathy adopted recommendations for estimation and prevention of cardioembolic stroke risk through the use of oral antithrombotic agents, 1 based on a prospective cohorte study of 1,043 patient with CCC. The total incidence reported in this event was 3.0%, or 0.56%/year. In the final risk model for cardioembolic stroke prediction, a score was calculated in which the presence of LV systolic dysfunction added two points, and apical aneurysm, alteration of the ventricular repolarization at the ECG and age > 48 years added one point for each alteration. Considering the risk-benefit ratio, warfarin would be Simões et. al. Chagas Disease Cardiomyopathy Int J Cardiovasc Sci. 2018;31(2)173-189 Review Article