Pharmacological interventions for treating heart failure in patients with Chagas cardiomyopathy.
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ABSTRACT:
SUBMITTER: Marti-Carvajal AJ
PROVIDER: S-EPMC6457883 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
Pharmacological interventions for treating heart failure in patients with Chagas cardiomyopathy.
Martí-Carvajal Arturo J AJ Kwong Joey S W JS
The Cochrane database of systematic reviews 20160708
<h4>Background</h4>Chagas disease-related cardiomyopathy is a major cause of morbidity and mortality in Latin America. Despite the substantial burden to the healthcare system, there is uncertainty regarding the efficacy and safety of pharmacological interventions for treating heart failure in people with Chagas disease. This is an update of a Cochrane review published in 2012.<h4>Objectives</h4>To assess the clinical benefits and harms of current pharmacological interventions for treating heart ...[more]
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Project description:Chronic Chagas cardiomyopathy (CCC) is the most frequent and severe clinical form of chronic Chagas disease, representing one of the leading causes of morbidity and mortality in Latin America, and a growing global public health problem. There is currently no approved treatment for CCC; however, omics technologies have enabled significant progress to be made in the search for new therapeutic targets. The metabolic alterations associated with pathogenic mechanisms of CCC and their relationship to cellular and immunopathogenic processes in cardiac tissue remain largely unknown. This exploratory study aimed to evaluate the potential underlying pathogenic mechanisms in the failing myocardium of patients with end-stage heart failure (ESHF) secondary to CCC by applying an untargeted metabolomic profiling approach. Cardiac tissue samples from the left ventricle of patients with ESHF of CCC etiology (n = 7) and healthy donors (n = 7) were analyzed using liquid chromatography-mass spectrometry. Metabolite profiles showed altered branched-chain amino acid and acylcarnitine levels, decreased fatty acid uptake and oxidation, increased activity of the pentose phosphate pathway, dysregulation of the TCA cycle, and alterations in critical cellular antioxidant systems. These findings suggest processes of energy deficit, alterations in substrate availability, and enhanced production of reactive oxygen species in the affected myocardium. This profile potentially contributes to the development and maintenance of a chronic inflammatory state that leads to progression and severity of CCC. Further studies involving larger sample sizes and comparisons with heart failure patients without CCC are needed to validate these results, opening an avenue to investigate new therapeutic approaches for the treatment and prevention of progression of this unique and severe cardiomyopathy.
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Project description:Physicians working in Europe and the United States should suspect Chagas heart failure in every patient coming from Latin America with chronic heart failure. Diagnosis should be confirmed by positive serology. Right bundle branch block and left anterior fascicular block on 12-lead electrocardiogram, enlarged cardiac silhouette with no pulmonary congestion on chest X-ray and left ventricular apical aneurysm on echocardiography are the distinctive features of this condition. The clinical course is poorer than that of non-Chagas heart failure; however, medical treatment is similar. Implantable cardioverter-defibrillators are useful in the primary and secondary prevention of sudden cardiac death. Cardiac resynchronisation therapy can be given to patients on optimal medical therapy and with lengthened QRS complex. Heart transplantation is the treatment of choice for patients with end-stage Chagas heart failure.
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Project description:BackgroundChronic Chagas cardiomyopathy (CCC) constitutes the most life-threatening consequence of the Trypanosoma cruzi infection. Our goal was to test in CCC the associations of the myocardial tissue phenotype with cardiac dysfunction, and heart failure (HF) severity, using cardiac magnetic resonance (CMR).MethodsWe performed a prospective observational cohort of patients with consecutive CCC with a CMR protocol, including ventricular function, myocardial T1, and late gadolinium enhancement (LGE). Extracellular volume (ECV), and intracellular water lifetime, τic, a measure of cardiomyocyte diameter, were compared to CCC disease progression, including Rassi score and New York Heart Association (NYHA) class. An exploratory prognostic analysis was performed to investigate the association of both ECV and τic with CV death.ResultsA total of 37 patients with intermediate-to-high-risk CCC were enrolled (Chagas Rassi score ≥7, mean left ventricle (LV) ejection fraction (EF) 32 ± 16%). Myocardial ECV (0.40 ± 0.07) was correlated with Rassi score (r = 0.43; P = 0.009), higher NYHA class, and LV EF (r = -0.51; P = 0.0015). τic decreased linearly with NYHA class (P = 0.007 for non-parametric test of linear trend) and showed a positive association with LV EF (r = 0.47; P = 0.004). Over a median follow-up of 734 days (range: 6-2,943 days), CV death or cardiac transplantation occurred in 10 patients. The Rassi score (heart rate [HR] = 1.3; 95% CI = [1.0, 1.8]; P = 0.028) and ECV (HR = 3.4 for 0.1 change, 95% CI = [1.1, 11.0], P = 0.039) were simultaneously associated with CV death.ConclusionIn patients with intermediate-to-high-risk CCC, an expanded ECV and regression of cardiomyocyte diameter were associated with worsening systolic function and HF severity, respectively. The exploratory analysis indicates that ECV may have a prognostic value to identify patients with CCC at a higher risk for cardiovascular events.
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Project description:Aims: We aimed to assess diabetes outcomes in heart failure (HF) patients with hypertrophic cardiomyopathy (HCM). Methods: The National Inpatient Sample database was analyzed to identify records from 2005 to 2015 of patients hospitalized for HF with concomitant HCM. We examined the prevalence of diabetes in those patients, assessed the temporal trend of in-hospital mortality, ventricular fibrillation, atrial fibrillation, and cardiogenic shock and compared diabetes patients to their non-diabetes counterparts. Results: Among patients with HF, 0.26% had HCM, of whom 29.3% had diabetes. Diabetes prevalence increased from 24.8% in 2005 to 32.7% in 2015. The mean age of patients with diabetes decreased from 71 ± 13 to 67.6 ± 14.2 (p < 0.01), but the prevalence of cardiovascular risk factors significantly increased. In-hospital mortality decreased from 4.3% to 3.2% between 2005 and 2015. Interestingly, cardiogenic shock, VF, and AF followed an upward trend. Age (OR = 1.04 [1.03-1.05]), female gender (OR = 1.50 [0.72-0.88]), and cardiovascular risk factors were associated with a higher in-hospital mortality risk in diabetes. Compared to non-diabetes patients, the ones with diabetes were younger and had more comorbidities. Unexpectedly, the adjusted risks of in-hospital mortality (aOR = 0.88 [0.76-0.91]), ventricular fibrillation (aOR = 0.79 [0.71-0.88]) and atrial fibrillation (aOR 0.80 [0.76-0.85]) were lower in patients with diabetes, but not cardiogenic shock (aOR 1.01 [0.80-1.27]). However, the length of stay was higher in patients with diabetes, and so were the total charges per stay. Conclusion: In total, we observed a temporal increase in diabetes prevalence among patients with HF and HCM. However, diabetes was paradoxically associated with lower in-hospital mortality and arrhythmias.
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Project description:Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients' myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.
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2007-10-31 | E-CVDE-1 | biostudies-arrayexpress