Chagas disease (CD) is the major cause of disability secondary to tropical diseases in young
adults from Latin America. In this region 20 million people are currently infected by T.
cruzi, the etiologic agent for CD. In Colombia, 18 percent of the population live in CD
endemic areas, 900,000 people are infected and over three million are at high risk of being
infected. Heart failure due to Chagas cardiomyopathy (CCM) is the main clinical form of CD in
Colombia. However, the incidence of CCM among T. cruzi infected people is unknown and the
mechanisms that lead from infection to CCM are uncertain. Besides the poor prognosis of CHF
due to Chagas disease, it is important to estimate the risk of complications and death in
patient infected with T. cruzi Unfortunately, few clinical studies have addressed this issue.
Most T. cruzi infected patients have mild or no clinical disease, however, the percentage of
infected people that will develop detectable cardiac abnormalities is approximately 30 to 40
percent, but only 20 percent of them will develop symptomatic cardiac involvement. Like CHF
from other causes, CHF due to CD responds to digital, diuretics and vasodilators therapy.
Also, some studies have shown that angiotensin-converting enzyme (ACE) inhibitors improve
survival in patients with moderate to severe CHF due to CD. Increased sympathetic drive
results in an increased risk of cardiac arrhythmia and sudden death. Beta-adrenoreceptor
antagonism seems to protect against the deleterious effects of chronic sympathetic
stimulation. The effects of the selective beta-adrenergic receptor blocker Bisoprolol on
cardiovascular mortality, hospital readmission due to progressive heart failure and
functional status in patients with CHF secondary to CCM has not been explored to-date. To
evaluate the benefit of Bisoprolol in CHF due to CCM, a cohort of T. cruzi seropositive
patients will be selected from several institutions in Colombia. Patients will be classified
according to a modified version of the Panamerican Health Organization recommendations for
patients with CCM. Overall one year mortality in patients with CHF due to Chagas disease has
been reported as 34 percent. However, one year mortality is only 3 percent in patients in
NYHA functional class II, 27 percent in those in NYHA functional class III, and 62 percent
among those in functional class IV (22). The sample size has been calculated assuming an
event rate of 40 percent in two years in the placebo group, and using a 95 percent confidence
level and power of 80 percent, we will need to recruit 250 patients per treatment arm to
detect a reduction of 30 percent in the risk of the primary outcome. The event rate we have
used to estimate sample size is similar to the expected two-year mortality in patients with
CHF due to Chagas disease in NYHA functional class II. Therefore, the estimated sample size
should be enough to measure significant changes in the composite primary outcome (death, HF
hospitalizations, SMVT, SCD). The recruitment process will follow guidelines set out by the
FCV Ethics Committee. Most participants will be recruited from the Chagas disease and the
Heart Failure clinics located in Bucaramanga, Bogotá and Cucuta. During the pretreatment
period an initial evaluation visit will be scheduled in which participants will sign consent
forms, baseline measurements and tests will be conducted at the FCV including blood pressure
measurements obtained with patients in the sitting and standing positions. Laboratory test
such as twelve-lead ECG will be recorded in each patient. Left ventricular ejection fraction
at rest will be determined by 2D echocardiography, using a modified Simpsons rule to
calculate LV volumes. Quality of life questionnaire will be performed two weeks apart during
baseline examination using the Minnesota living with heart failure questionnaire. Minimum of
two 6-minutes corridor walk test once a week over a two-week period will be performed to
measure the functional class. During the treatment period patients will be randomly assigned
to receive double-blind Bisoprolol or placebo, initially taking a total daily dose of 2.5
mgrs qd. The dose will be increased every two weeks to 5 up to 7.5 and 10 mgrs qd (maximum
maintenance dose). Follow-up assessment will include clinical check-up, and blood collection
for future measurements of inflammatory reactants and markers. Quality of life measurements
will be obtained at six months. Following the descriptive analysis we will compare the
patient survival and hospitalization rates using Kaplan-Meier estimates and survival graphs.
Cox regression will be used for the multivariate analysis of time to death and time to
hospitalization. This analysis will allow us to explore the pattern of changes in patients
with chronic heart failure due to Chagas disease such as the effect of beta-blockers in this
special type of cardiomyopathy.