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Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy.

ABSTRACT: Chronic Chagas cardiomyopathy in humans is characterized by segmental left ventricular wall motion abnormalities (WMA), mainly in the early stages of disease. This study aimed at investigating the detection of WMA and its correlation with the underlying histopathological changes in a chronic Chagas cardiomyopathy model in hamsters.Female Syrian hamsters (n=34) infected with 3.5×10(4) or 10(5) blood trypomastigote Trypanosoma cruzi (Y strain) forms and an uninfected control group (n=7) were investigated. After 6 or 10 months after the infection, the animals were submitted to in vivo evaluation of global and segmental left ventricular systolic function by echocardiography, followed by euthanasia and histological analysis for quantitative assessment of fibrosis and inflammation with tissue sampling in locations coinciding with the left ventricular wall segmentation employed at the in vivo echocardiographic evaluation. Ten of the 34 infected animals (29%) showed reduced left ventricular ejection fraction (<73%). Left ventricular ejection fraction was more negatively correlated with the intensity of inflammation (r=-0.63; P<0.0001) than with the extent of fibrosis (r=-0.36; P=0.036). Among the 24 animals with preserved left ventricular ejection fraction (82.9±5.5%), 8 (33%) showed segmental WMA predominating in the apical, inferior, and posterolateral segments. The segments exhibiting WMA, in comparison to those with normal wall motion, showed a greater extent of fibrosis (9.3±5.7% and 7±6.3%, P<0.0001) and an even greater intensity of inflammation (218.0±111.6 and 124.5±84.8 nuclei/mm², P<0.0001).Isolated WMA with preserved global systolic left ventricular function is frequently found in Syrian hamsters with experimental chronic Chagas cardiomyopathy whose underlying histopathological features are mainly inflammatory.

SUBMITTER: de Oliveira LF

PROVIDER: S-EPMC4859397 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other

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Project description:BackgroundThe term "end stage" has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when left ventricular ejection fraction is <50%. The prognosis of HCM-LVSD has reportedly been poor, but because of its relative rarity, the natural history remains incompletely characterized.MethodsData from 11 high-volume HCM specialty centers making up the international SHaRe Registry (Sarcomeric Human Cardiomyopathy Registry) were used to describe the natural history of patients with HCM-LVSD. Cox proportional hazards models were used to identify predictors of prognosis and incident development.ResultsFrom a cohort of 6793 patients with HCM, 553 (8%) met the criteria for HCM-LVSD. Overall, 75% of patients with HCM-LVSD experienced clinically relevant events, and 35% met the composite outcome (all-cause death [n=128], cardiac transplantation [n=55], or left ventricular assist device implantation [n=9]). After recognition of HCM-LVSD, the median time to composite outcome was 8.4 years. However, there was substantial individual variation in natural history. Significant predictors of the composite outcome included the presence of multiple pathogenic/likely pathogenic sarcomeric variants (hazard ratio [HR], 5.6 [95% CI, 2.3-13.5]), atrial fibrillation (HR, 2.6 [95% CI, 1.7-3.5]), and left ventricular ejection fraction <35% (HR, 2.0 [95% CI, 1.3-2.8]). The incidence of new HCM-LVSD was ?7.5% over 15 years. Significant predictors of developing incident HCM-LVSD included greater left ventricular cavity size (HR, 1.1 [95% CI, 1.0-1.3] and wall thickness (HR, 1.3 [95% CI, 1.1-1.4]), left ventricular ejection fraction of 50% to 60% (HR, 1.8 [95% CI, 1.2, 2.8]-2.8 [95% CI, 1.8-4.2]) at baseline evaluation, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging (HR, 2.3 [95% CI, 1.0-4.9]), and the presence of a pathogenic/likely pathogenic sarcomeric variant, particularly in thin filament genes (HR, 1.5 [95% CI, 1.0-2.1] and 2.5 [95% CI, 1.2-5.1], respectively).ConclusionsHCM-LVSD affects ?8% of patients with HCM. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death equivalent an estimated median time of 8.4 years after developing systolic dysfunction. In addition to clinical features, genetic substrate appears to play a role in both prognosis (multiple sarcomeric variants) and the risk for incident development of HCM-LVSD (thin filament variants).

Project description:BackgroundDespite advancements in pharmacological and device-based treatment, heart failure (HF) continues to impose an enormous burden for health care system worldwide. Decompensation of HF is one of the main causes of hospitalization, therefore the identification of patients with the highest risk of such complication is still of great clinical importance. The prognostic significance and utility of global longitudinal strain (GLS) has been previously studied in patients with the broad spectrum of cardiovascular diseases in various endpoints, however its role in assessing the risk of hospitalization due to HF exacerbation of optimally treated outpatients has not been fully explored. Therefore, the aim of the study was to verify whether the GLS of the left ventricle (LV) derived by 2D speckle tracking echocardiography has, independently of other well-known clinical parameters, an additional impact on the risk of HF decompensation in stable patients with LV systolic dysfunction of ischemic origin.MethodsIn 193 clinically stable HF outpatients with LV ejection fraction (LVEF) ≤ 50%, GLS, additionally to other clinical parameters, was analyzed. During 34 (14-71) months of follow-up, 58 patients were hospitalized due to HF decompensation (EVENT).ResultsEVENT was significantly associated with age, QRS width, NYHA functional class, left atrium diameter, LV systolic and diastolic volume, LVEF, hemoglobin, brain natriuretic peptide, diuretic treatment, absence of beta-blockers, impaired renal function and history of diabetes in univariate Cox analyzes. GLS with pre-specified cut-off value of -9.4% was also significantly associated with the EVENT (HR 15.16; 95% CI 1.81-126.91). After adjusting for above-mentioned parameters GLS was still a significant predictor of hospitalization due to HF decompensation.ConclusionsGLS measurement can provide incremental information on the risk of HF decompensation in stable outpatients with LV systolic dysfunction of ischemic origin.

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Histopathological Correlates of Global and Segmental Left Ventricular Systolic Dysfunction in Experimental Chronic Chagas Cardiomyopathy.

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