Longitudinal strain by speckle tracking and echocardiographic parameters as predictors of adverse cardiovascular outcomes in chronic Chagas cardiomyopathy

To analyze the prognostic value of left ventricular global longitudinal strain (LV-GLS) and other echocardiographic parameters to predict adverse outcomes in chronic Chagas cardiomyopathy (CCM). Prospective cohort study conducted in 177 consecutive patients with different CCM stages. Transthoracic echocardiography measurements were obtained following the American Society of Echocardiography recommendations. By speckle-tracking echocardiography, LV-GLS was obtained from the apical three-chamber, apical two-chamber, and apical four-chamber views. The primary composite outcome (CO) was all-cause mortality, cardiac transplantation, and a left ventricular assist device implantation. After a median follow-up of 42.3 months (Q1 = 38.6; Q3 = 52.1), the CO incidence was 22.6% (95% CI 16.7–29.5%, n = 40). The median LV-GLS value was − 13.6% (Q1 = − 18.6%; Q3 = − 8.5%). LVEF, LV-GLS, and E/e′ ratio with cut-off points of 40%, − 9, and 8.1, respectively, were the best independent CO predictors. We combined these three echocardiographic markers and evaluated the risk of CO according to the number of altered parameters, finding a significant increase in the risk across the groups. While in the group of patients in which all these three parameters were normal, only 3.2% had the CO; those with all three abnormal parameters had an incidence of 60%. We observed a potential incremental prognostic value of LV-GLS in the multivariate model of LVEF and E/e′ ratio, as the AUC increased slightly from 0.76 to 0.79, nevertheless, this difference was not statistically significant (p = 0.066). LV-GLS is an important predictor of adverse cardiovascular events in CCM, providing a potential incremental prognostic value to LVEF and E/e′ ratio when analyzed using optimal cut-off points, highlighting the potential utility of multimodal echocardiographic tools for predicting adverse outcomes in CCM.

The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

Background: The Trypanosoma cruzi infection renders the transfer of the mitochondrion kinetoplast DNA minicircle sequences into the host’s genome. The Aves are refractory to the infection, but chicks hatched from the T. cruzi inoculated eggs integrate the DNA minicircle sequences into the germ line cells. Rabbits, mice and chickens with the minicircle sequences mutations develop the Chagas cardiomyopathy and the DNA transfer underpins the heart disease. Methodology: The PCR with the specific primer sets revealed the Protist nuclear DNA and the kinetoplast DNA in the agarose gels bands probed with the radiolabel specific sequences from tissues of the T. cruzi-infected rabbits and of the mice. A targetprimer TAIL-PCR amplification employing primer sets from the chickens, rabbits and mice, in combination with primer sets from the the T. cruzi kinetoplast minicircle sequences was used. This approach led us to disclose the integration sites of the kinetoplast DNA biomarker, then, used to monitor the effect of multidrug treatment of the T. cruzi infected mice. Principal findings: The Southern hybridization, clone and sequence of the amplification products revealed the DNA minicircle sequences integrations sites in the LINE transposable elements. An array of inhibitors of eukaryote cells division was used to arrest the DNA transfer. It was shown that nine out of 12 inhibitors prevented the kinetoplast DNA integration into the macrophage genome. The multidrug treatment of the acutely T. cruzi-infected mice with Benznidazole, Azidothymidine and Ofloxacin lessened circa 2.5-fold the rate of the minicircle sequences integrations in the mouse genome and inhibited the rejection of the target heart cells. Conclusion and significance: The T. cruzi mitochondrion kinetoplast minicircle sequences transfer driven pathogenesis of Chagas disease is an ancient Cross-Kingdom DNA phenomenon of evolution and, therefore, paradigm research with effective purposing inhibitors is needed.

Cardiovascular Biomarkers and Diastolic Dysfunction in Patients With Chronic Chagas Cardiomyopathy

Background: Chronic Chagas Cardiomyopathy is a unique form of cardiomyopathy, with a significantly higher mortality risk than other heart failure etiologies. Diastolic dysfunction (DD) plays an important role in the prognosis of CCM; however, the value of serum biomarkers in identifying and stratifying DD has been poorly studied in this context. We aimed to analyze the correlation of six biochemical markers with diastolic function echocardiographic markers and DD diagnosis in patients with CCM.Methods: Cross-sectional study of 100 adults with different stages of CCM. Serum concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), high-sensitivity troponin T (hs-cTnT), soluble (sST2), and cystatin-C (Cys-c) were measured. Tissue Doppler imaging was used to measure echocardiographic parameters indicating DD. Multivariate logistic regression models adjusted by age, sex, BMI, and NYHA classification were used to evaluate the association between the biomarkers and DD.Results: From the total patients included (55% male with a median age of 62 years), 38% had a preserved LVEF, but only 14% had a normal global longitudinal strain. Moreover, 64% had a diagnosis of diastolic dysfunction, with most of the patients showing a restrictive pattern (n = 28). The median levels of all biomarkers (except for sST2) were significantly higher in the group of patients with DD. Higher levels of natural log-transformed NTproBNP (per 1-unit increase, OR = 3.41, p < 0.001), Hs-cTnT (per 1-unit increase, OR = 3.24, p = 0.001), NGAL (per 1-unit increase, OR = 5.24, p =0.003), and Cys-C (per 1-unit increase, OR = 22.26, p = 0.008) were associated with increased odds of having diastolic dysfunction in the multivariate analyses. Finally, NT-proBNP had the highest AUC value (88.54) for discriminating DD presence.Conclusion: Cardiovascular biomarkers represent valuable tools for diastolic dysfunction assessment in the context of CCM. Additional studies focusing mainly on patients with HFpEF are required to validate the performance of these cardiovascular biomarkers in CCM, allowing for an optimal assessment of this unique population.

Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy

Chagas disease is a parasitic infection caused by the intracellular protozoan Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC) is the most severe manifestation of the disease, developed by approximately 20-40% of patients and characterized by occurrence of arrhythmias, heart failure and death. Despite having more than 100 years of discovery, Chagas disease remains without an effective treatment, especially for patients with CCC. Since the pathogenesis of CCC depends on a parasite-driven systemic inflammatory profile that leads to cardiac tissue damage, the use of immunomodulators has become a rational alternative for the treatment of CCC. In this context, different classes of drugs, cell therapies with dendritic cells or stem cells and gene therapy have shown potential to modulate systemic inflammation and myocarditis in CCC models. Based on that, the present review provides an overview of current reports regarding the use of immunomodulatory agents in treatment of CCC, bringing the challenges and future directions in this field.