Matrix metalloproteinases 2 and 9 as diagnostic markers in the progression to Chagas cardiomyopathy.

BACKGROUND: Infection with the Trypanosoma cruzi parasite is endemic in parts of Central and South America. Approximately 30% of those infected develop Chagas cardiomyopathy, the most common cause of heart failure in this region. No suitable biomarker is available that reflects the evolution of the disease. Although there is substantial evidence of a strong inflammatory reaction following infection that could activate matrix metalloproteinases (MMPs), their role in the development of Chagas cardiomyopathy is unknown. METHODS: A cross-sectional study was conducted in Bucaramanga, Colombia, from 2002 to 2006, including 144 patients at different stages of Chagas disease and 44 control patients. The potential enzyme activities of MMP-2 and MMP-9 in plasma samples were determined by gelatin zymography. Clinical data including T cruzi serology, electrocardiograms, and echocardiograms were recorded for all patients. RESULTS: Densitometric analysis of potential enzyme activities in plasma samples showed a significant increase of 72-kd MMP-2 (P < .001) and 92-kd MMP-9 (P < .001) in T cruzi seropositive patients compared with control subjects. Matrix metalloproteinase 9 showed significantly increased activity in patients with abnormal electrocardiogram (P < .004) and with dilated cardiomyopathy compared (P < .001) with controls. Analysis of the MMP-2 and MMP-9 results in relation to clinical data revealed that abnormal heart relaxation correlated positively with high MMP-2 levels in patients with dilated cardiomyopathy (r = 0.75, P < .01). CONCLUSIONS: Plasma MMP-2 and MMP-9 both appear to be useful biomarkers for detecting the advent and progression of cardiomyopathy in T cruzi-infected individuals.

Clinical, electrocardiographic and echocardiographic abnormalities in Latin American migrants with newly diagnosed Chagas disease 2005-2009, Barcelona, Spain.

Following Latin American migration, Chagas disease has inevitably appeared in non-endemic countries in Europe and elsewhere. New policies are necessary to prevent transmission in those countries but the long, often undetected chronic period of the early stages of the disease also renders epidemiological studies important. The main objective of our study was to determine the presence of clinical, electrocardiogram (ECG) and echocardiographic abnormalities in a population of Latin American migrants infected with Trypanosoma cruzi at the moment of diagnosis. We performed a hospital-based observational study of 100 adult patients with newly diagnosed Chagas infection between January 2005 and December 2009. Thirty-seven patients were classified within the Brazilian Consensus on Chagas cardiomyopathy early cardiac stages (A or B1) and 49 presented pathological findings (stage B2) according to the Panamerican Health Organization Classification. Overall, 49 patients showed ECG and/or echocardiographic alterations. The presence of ECG and ecocardiographic alterations were significantly associated (p=0.038). The most frequent ECG and echocardiographic findings were right bundle branch block (12 cases) and impaired left ventricular wall relaxation (24 cases), respectively. In conclusion, ECG and echocardiographic alterations coherent with Chagas cardiomyopathy were found in a large proportion of newly diagnosed Latin American migrants infected with T. cruzi. In the mid-term, Chagas disease might become an important cause of chronic cadiomyopathy in our attendance area.

Nuevas perspectivas en el manejo terapéutico de la enfermedad de chagas / New perspectives in the therapeutic management of the Chagas disease

Desde hace un par de décadas y más aun en los últimos cinco años, se ha desarrollado un gran número de estudios que demuestran la actividad tripanocida de diversas drogas, algunas nuevas, muchas viejas, lo cual aunado al conocimiento acerca de la persistencia parasitaria de Trypanosoma cruzi en tejido miocárdico, entre otros, durante las fases crónicas de la enfermedad, permiten hacer patente que existe un nuevo paradigma, nuevas aproximaciones al manejo terapéutico del paciente con enfermedad de Chagas. En el presente artículo se revisan las principales bases que sustentan dichas perspectivas terapéuticas en la tripanosomiasis americana.

For the last couple of decades and particularly during the last five years, it has been reported a significant number of studies demonstrating the trypanocide activity of a large number of drugs, some of them news, others older; which jointly with the knowledge, also of recent date, about parasitary persistence of Trypanosoma cruzi at myocardial tissues, and others, in chronic phase of disease, are letting to do patent that exist a new paradigm, new approaches of the therapeutic management of Chagas’ disease patient. In current article main basis sustaining those therapeutic perspectives in American trypanosomiasis are reviewed.

Cardiac autonomic impairment and early myocardial damage involving the right ventricle are independent phenomena in Chagas' disease.

Cardiac autonomic impairment and right side heart failure are prominent features in patients with Chagas' disease, but no causal relationship between these phenomena has been disclosed and the pathophysiology of such manifestations is unclear. Aim of study was to assess the cardiac autonomic control and biventricular function in chagasic patients in early stages of the disease, using radionuclide angiography, Valsalva manoeuvre, head-up tilt and baroreflex sensitivity evaluation. Thirty-one chagasic patients with no clinical signs of Chagas' heart disease-16 in the indeterminate phase and 15 with sole organic digestive involvement-were studied, and results compared with those obtained in 14 normal volunteers. No significant differences were observed among the three groups, in regard to any systolic or diastolic parameter of LV function, including ejection fraction, peak ejection and filling rates and correspondent times, time to end-systole, and the standard deviation of phase values. The indeterminate and digestive groups of chagasics had significantly lower right ventricular ejection fraction (45.7 +/- 6.3 and 46.2 +/- 10.1 respectively) and peak ejection rate (respectively 2.8 +/- 0.6 and 2.9 +/- 0.6) and higher right ventricular phase standard deviation (22.4 +/- 5.9 and 20.1 +/- 5.6 degrees, respectively), as compared with the control group (53.6 +/- 4.3, 3.5 +/- 0.5, and 15.8 +/- 3.8 respectively for right ventricular ejection fraction, peak ejection rate and phase standard deviation). No significant differences were found between the results of autonomic evaluation in the control and indeterminate groups of chagasic patients. The group of digestive disease patients showed abnormally lower Valsalva ratio (1.5 +/- 0.15), baroreflex sensitivity (8.85 +/- 2.05 ms/mmHg) and parasympathetically-dependent heart rate response to tilt (8.85 +/- 8.42 beats/mm) and higher Valsalva delay (15.67 +/- 1.35 s) values, compared with the control group (respectively 1.85 +/- 0.49, 20.23 +/- 12.66 ms/mmHg, 21.61 +/- 5.77 beats/mm and 10.1 +/- 2.5 s). Thus, cardiac autonomic impairment is a prominent feature in chagasic patients with the digestive but not the indeterminate form of Chagas' disease. It bears no causative relationship to the early myocardial damage that is apparent only regarding right ventricular function, in both groups of patients. Early right ventricular dysfunction is a likely mechanism for the marked predominance of systemic over pulmonary congestion when heart failure supervenes in patients with Chagas' disease.

Seroepidemiological and clinical study of Chagas diseases in Nicaragua

Con el objetivo de determinar la prevalencia, perfil imunologico de la poblacion y conocer las alteraciones electrocardiograficas; se realizo un estudio seroepidemiologico y clinico de la enfermedad de Chagas en tres localidades ubicadas al Norte, Oriente y Occidente de Nicaragua. Como muestra se tomo suero a 803 personas, a las que se les realizo busqueda de anticuerpos anti T. cruzi por Immunoflurescencia (IFI) y hemaglutinacion indirecta (HAI)...

Utilidad de la ecocardiografia en la cardiopatia chagasica cronica / Use of the ultrasound ecchocardiography in chagasic cardiopathy

Considerando que el compromiso cardiaco cosntituye la mas importante manifestacion de la fase cronica de la enfermedad de chagas, el aporte de la ecocardiografia en la valoracion de la cardiografia chagasica cronica ha permitido la deteccion precoz del compromiso miocardico, en etapas en que otros metodos de diagnostico no eran utiles, tambien la valoracion de la funcion ventricular constituye un parametro importante en estos casos y la posibilidad de efectuar seguimiento mediante este metodo de diagnostico no invasivo es de gran ayuda. El objetivo del presente estudio de revision retrospectiva es establecer cuales son las principales alteraciones ecocardiograficas en las diferentes fases de la enfermedad de chagas enfatizando en la evaluacion de funcion ventricular y, al mismo tiempo, comparar estos parametros con similares de la literatura internacional. El presente trabajo realizado en base a la experiencia de un estudio sobre 98 pacientes evaluados en el IBBA y 22 pacientes evaluados en el Instituto Nal. del Torax, utilizando ecocardiografia modo M y bidimensional, los pacientes fueron divididos en grupos de acuerdo a la clasificacion OMS/OPS de la cariopatia chagasica cronica. Los parametros ecocardiograficos analizados y comparados con los reportados de la literatura, nos han permitido plantear un espectrum de hallazgos ecocardiograficos en las diferentes fases de la cardiopatia chagasica cronica.

Estudio clínico de seguimiento a lo largo de la enfermedad de chagas en grandes alturas / Clinic study at Chagas disease at high altitude

Se efectuó un seguimiento clínico, electrocardiográfico en 64 pacientes ambulatorios, Clase I-II procedentes de áreas endémicas de enfermedad de Chagas a baja altitud, y actualmente residentes en altura (3,700 m) con serología positiva para enfermedad de Chagas, seguidos durante 6 años (2 a 12 años). Clínicamente no se observó desmejoría sintomática, ni insuficiencia cardíaca durante el seguimiento. El electrocardiograma fue normal en 27 por ciento de los casos al principio del seguimiento, persistiendo normal en el 19 por ciento hasta el fin del estudio. Las alteraciones electrocardiográficas observadas incluyeron: Bradicardia sinusual, hemobloqueo ántero-superior izquierdo, bloquepo de rama derecha, extrasistolia ventricular. La bradicardia sinusual constituye la característica electrocardiográfica más importante en este grupo. Los transtornos de conducción presentes en 20 por ciento de los pacientes al inicio del estudio, se observaron en 25 por ciento al concluir el mismo. Los pacientes con hemibloqueo ántero-superior izquierdo (14 por ciento del grupo al inicio del seguimiento, 15 por ciento al final) no presentaron evolución desfavorable, ninguno sintomática ni electrocardiográfica; los pacientes con bloqueo de Rama Derecha (6 por ciento al inicio, y 10,7 por ciento al final), tampoco tuvieron evolución desfavorable, ninguno desarrolló bloqueo aurículo ventricular completo. El ecocardiograma no mostró diferencias significativas en las dimensiones de cavidades ventriculares, tampoco en el grosor de paredes del ventrículo izquierdo. La función ventricular: fracción de eyección y fracción de acortamiento, no se detrioró durante este período. El seguimiento de este grupo de pacientes con enfermedad de Chagas mostró una evolución benigna, sin deterioro sintomático, ni alteraciones significativas del electrocardiograma ni ecocardiograma. No se detectó compromiso de la función ventricular ni insuficiencia cardíaca en el transcurso del estudio