Cardiac Troponin and Treatment Effects of Omecamtiv Mecarbil: Results From the GALACTIC-HF Study.

BACKGROUND: Omecamtiv mecarbil improves outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We examined the relationship between baseline troponin levels, change in troponin levels over time and the treatment effect of omecamtiv mecarbil in patients enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in Heart Failure (GALACTIC-HF) trial (NCT02929329). METHODS: GALACTIC-HF was a double-blind, placebo-controlled trial that randomized 8256 patients with symptomatic HFrEF to omecamtiv mecarbil or placebo. High-sensitivity troponin I (cTnI) was measured serially at a core laboratory. We analyzed the relationship between both baseline cTnI and change in cTnI concentrations with clinical outcomes and the treatment effect of omecamtiv mecarbil. RESULTS: Higher baseline cTnI concentrations were associated with a risk of adverse outcomes (hazard ratio for the primary endpoint of time to first HF event or CV death = 1.30; 95% CI 1.28, 1.33; P < 0.001 per doubling of baseline cTnI). Although the incidence of safety outcomes was higher in patients with higher baseline cTnI, there was no difference between treatment groups. Treatment with omecamtiv mecarbil led to a modest increase in cTnI that was related to plasma concentrations of omecamtiv mecarbil, and it peaked at 6 weeks. An increase in troponin from baseline to week 6 was associated with an increased risk of the primary endpoint (P < 0.001), which was similar, regardless of treatment assignment (P value for interaction = 0.2). CONCLUSIONS: In a cohort of patients with HFrEF, baseline cTnI concentrations were strongly associated with adverse clinical outcomes. Although cTnI concentrations were higher in patients treated with omecamtiv mecarbil, we did not find a differential effect of omecamtiv mecarbil on either safety or efficacy based on baseline cTnI status or change in cTnI.

Detection of Early Diffuse Myocardial Fibrosis and Inflammation in Chagas Cardiomyopathy with T1 Mapping and Extracellular Volume.

Purpose: To evaluate myocardial T1 mapping and extracellular volume (ECV) parameters in different stages of Chagas cardiomyopathy and determine whether they are predictive of disease severity and prognosis. Materials and Methods: Prospectively enrolled participants (July 2013 to September 2016) underwent cine and late gadolinium enhancement (LGE) cardiac MRI and T1 mapping with a precontrast (native) or postcontrast modified Look-Locker sequence. The native T1 and ECV values were measured among subgroups that were based on disease severity (indeterminate, Chagas cardiomyopathy with preserved ejection fraction [CCpEF], Chagas cardiomyopathy with midrange ejection fraction [CCmrEF], and Chagas cardiomyopathy with reduced ejection fraction [CCrEF]). Cox proportional hazards regression and the Akaike information criterion were used to determine predictors of major cardiovascular events (cardioverter defibrillator implant, heart transplant, or death). Results: In 107 participants (90 participants with Chagas disease [mean age ± SD, 55 years ± 11; 49 men] and 17 age- and sex-matched control participants), the left ventricular (LV) ejection fraction and the extent of focal and diffuse or interstitial fibrosis were correlated with disease severity. Participants with CCmrEF and participants with CCrEF showed significantly higher global native T1 and ECV values than participants in the indeterminate, CCpEF, and control groups (T1: 1072 msec ± 34 and 1073 msec ± 63 vs 1010 msec ± 41, 1005 msec ± 69, and 999 msec ± 46; ECV: 35.5% ± 3.6 and 35.0% ± 5.4 vs 25.3% ± 3.5, 28.2% ± 4.9, and 25.2% ± 2.2; both P < .001). Remote (LGE-negative areas) native T1 and ECV values were also higher (T1: 1056 msec ± 32 and 1071 msec ± 55 vs 1008 msec ± 41, 989 msec ± 96, and 999 msec ± 46; ECV: 30.2% ± 4.7 and 30.8% ± 7.4 vs 25.1% ± 3.5, 25.1% ± 3.7, and 25.0% ± 2.2; both P < .001). Abnormal remote ECV values (>30%) occurred in 12% of participants in the indeterminate group, which increased with disease severity. Nineteen combined outcomes were observed (median follow-up time: 43 months), and a remote native T1 value greater than 1100 msec was independently predictive of combined outcomes (hazard ratio, 12 [95% CI: 4.1, 34.2]; P < .001). Conclusion: Myocardial native T1 and ECV values were correlated with Chagas disease severity and may serve as markers of myocardial involvement in Chagas cardiomyopathy that precede LGE and LV dysfunction.Keywords: MRI, Cardiac, Heart, Imaging Sequences, Chagas Cardiomyopathy Supplemental material is available for this article. © RSNA, 2023.

Effect of exercise training on cardiovascular autonomic and muscular function in subclinical Chagas cardiomyopathy: a randomized controlled trial.

PURPOSE: Patients with chronic chagasic cardiomyopathy with preserved ventricular function present with autonomic imbalance. This study evaluated the effects of exercise training (ET) in restoring peripheral and cardiac autonomic control and skeletal muscle phenotype in patients with subclinical chronic chagasic cardiomyopathy. METHODS: This controlled trial (NCT02295215) included 24 chronic chagasic cardiomyopathy patients who were randomized www.random.org/lists/ into two groups: those who underwent exercise training (n = 12) and those who continued their usual activities (n = 12). Eight patients completed the exercise training protocol, and 10 patients were clinically followed up for 4 months. Muscular sympathetic nerve activity was measured by microneurography and muscle blood flow (MBF) using venous occlusion plethysmography. The low-frequency component of heart rate variability in normalized units (LFnuHR) reflects sympathetic activity in the heart, and the low-frequency component of systolic blood pressure variability in normalized units reflects sympathetic activity in the vessels. The infusion of vasoactive drugs (phenylephrine and sodium nitroprusside) was used to evaluate cardiac baroreflex sensitivity, and a vastus lateralis muscle biopsy was performed to evaluate atrogin-1 and MuRF-1 gene expression. RESULTS: The baroreflex sensitivity for increases (p = 0.002) and decreases (p = 0.02) in systolic blood pressure increased in the ET group. Muscle blood flow also increased only in the ET group (p = 0.004). Only the ET group had reduced resting muscular sympathetic nerve activity levels (p = 0.008) and sympathetic activity in the heart (LFnu; p = 0.004) and vessels (p = 0.04) after 4 months. Regarding skeletal muscle, after 4 months, participants in the exercise training group presented with lower atrogin-1 gene expression than participants who continued their activities as usual (p = 0.001). The reduction in muscular sympathetic nerve activity was positively associated with reduced atrogin-1 (r = 0.86; p = 0.02) and MuRF-1 gene expression (r = 0.64; p = 0.06); it was negatively associated with improved baroreflex sensitivity both for increases (r = -0.72; p = 0.020) and decreases (r = -0.82; p = 0.001) in blood pressure. CONCLUSIONS: ET improved cardiac and peripheral autonomic function in patients with subclinical chagasic cardiomyopathy. ET reduced MSNA and sympathetic activity in the heart and vessels and increased cardiac parasympathetic tone and baroreflex sensitivity. Regarding peripheral muscle, after 4 months, patients who underwent exercise training had an increased cross-sectional area of type I fibers and oxidative metabolism of muscle fibers, and decreased atrogin-1 gene expression, compared to participants who continued their activities as usual. In addition, the reduction in MSNA was associated with improved cardiac baroreflex sensitivity, reduced sympathetic cardiovascular tone, and reduced atrogin-1 and MuRF-1 gene expression. TRIAL REGISTRATION: ID: NCT02295215. Registered in June 2013.

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

BACKGROUND: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS: During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.).

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction: GALACTIC-HF baseline characteristics and comparison with contemporary clinical trials.

AIMS: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials. METHODS AND RESULTS: Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N-terminal pro-B-type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC-HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m2 (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594). CONCLUSIONS: GALACTIC-HF enrolled a well-treated, high-risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation.

Left Atrial Function in Patients with Chronic Chagasic Cardiomyopathy / Função Atrial Esquerda em Pacientes com Miocardiopatia Chagásica Crônica

Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks.

A doença de Chagas é uma causa de miocardiopatia dilatada, sendo ainda pouco conhecida a função do átrio esquerdo (AE) nessa doença.

Left Atrial Function in Patients with Chronic Chagasic Cardiomyopathy.

BACKGROUND: Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks. OBJECTIVE: To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions. METHODS: 10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging. RESULTS: Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e' (average) with the reservoir and pump functions (TEF and AEF), and a positive correlation of e' (average) with s' wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions. CONCLUSION: An impairment of LA functions in Chagas cardiomyopathy was observed.

Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.

BACKGROUND: Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

Anomalous right coronary artery arising from the pulmonary artery and constrictive pericarditis: an unusual association.

The association of anomalous right coronary artery originating from the pulmonary artery and constrictive pericarditis has never been showed in the literature. We present the first case of this unusual association in a patient with right heart failure. After diagnosis, the patient was referred to surgery and underwent phrenic-to-phrenic pericardiectomy; graft implant of right internal thoracic artery to right coronary artery; and ligation of the anomalous origin of the right coronary artery from the pulmonary artery. Such procedures solved the potential risk of sudden death related to anomalous right coronary artery originating from the pulmonary artery and alleviated the symptoms of heart failure caused by constrictive pericarditis.

Artéria coronária direita anômala com origem na artéria pulmonar e pericardite constritiva: uma associação inusitada / Anomalous right coronary artery arising from the pulmonary artery and constrictive pericarditis: an unusual association

A associação da artéria coronária direita anômala com origem na artéria pulmonar e pericardite constritiva ainda não foi descrita na literatura. Apresentamos aqui o primeiro caso dessa associação inusitada em um paciente com quadro de insuficiência cardíaca direita. Após o diagnóstico, o paciente foi encaminhado para tratamento cirúrgico, sendo submetido a pericardiectomia frênico a frênico, implante de enxerto da artéria mamária interna direita para a coronária direita e ligadura da origem anômala da coronária direita da artéria pulmonar. Tais procedimentos resolveram o potencial risco de morte súbita pela anomalia coronária e aliviaram os sintomas de insuficiência cardíaca causados pela pericardite constritiva.

The association of anomalous right coronary artery originating from the pulmonary artery and constrictive pericarditis has never been showed in the literature. We present the first case of this unusual association in a patient with right heart failure. After diagnosis, the patient was referred to surgery and underwent phrenic-to-phrenic pericardiectomy; graft implant of right internal thoracic artery to right coronary artery; and ligation of the anomalous origin of the right coronary artery from the pulmonary artery. Such procedures solved the potential risk of sudden death related to anomalous right coronary artery originating from the pulmonary artery and alleviated the symptoms of heart failure caused by constrictive pericarditis.

Prognostic value of the collagen volume fraction in hypertrophic cardiomyopathy.

BACKGROUND: In hypertrophic cardiomyopathy (HCM), interstitial myocardial fibrosis is an important histological modification that has been associated with sudden death and evolution toward myocardial dilation. OBJECTIVE: To prospectively evaluate the prognostic value of the collagen volume fraction in HCM. METHODS: An endomyocardial biopsy of the right ventricle was successfully performed in 21 symptomatic patients with HCM. The myocardial collagen volume fraction (CVF) was determined by histology. The CVF was also determined in fragments of nine normal hearts from subjects deceased from non-cardiac causes. The patients were divided into above-median CVF and below-median CVF groups, and their clinical and echocardiographic characteristics and survival curves were compared. RESULTS: Among the patients, the CVF ranged from 1.86% to 29.9%, median 6.19%; in normal hearts, from 0.13% to 1.46%, median 0.61% (p <0.0001 between HCM and control). There were no significant correlations between CVF and baseline echocardiographic measures. Patients with CVF < or =6.19% and CVF> 6.19% were compared and no baseline differences were observed. However, after an average follow-up period of 110 months, four deaths occurred (two sudden, two due to heart failure) in the group with increased CVF, whereas the patients of the group with lower CVF were all alive at the end of the period (p = 0.02). CONCLUSION: For the first time, myocardial fibrosis was prospectively associated with a worse prognosis in patients with HCM. Efforts should be directed to the quantification of myocardial fibrosis in HCM, on the premise that its association with the prognosis can aid in the stratification of risk for defibrillator implantation, and in the prescription of drugs that potentially promote myocardial repair.

Valor prognóstico da fração de volume de colágeno na cardiomiopatia hipertrófica / Prognostic value of the collagen volume fraction in hypertrophic cardiomyopathy / Valor pronóstico de la fracción de volumen de colágeno en la cardiomiopatía hipertrófica

FUNDAMENTO: Na cardiomiopatia hipertrófica (CMH), a fibrose miocárdica intersticial é uma importante alteração histológica que tem sido associada com morte súbita e evolução para dilatação. OBJETIVO: Avaliar, prospectivamente, o valor prognóstico da fração de colágeno na CMH. MÉTODOS: Biópsia endomiocárdica do ventrículo direito foi realizada com sucesso em 21 pacientes sintomáticos com CMH. A fração de volume de colágeno (FVC) miocárdico foi determinada por histologia. A FVC também foi determinada em fragmentos de nove corações normais de indivíduos falecidos por causas não-cardíacas. Os pacientes foram divididos em grupos supra e infra-medianos em relação à FVC, sendo comparadas as características clínico-ecocardiográficas e as curvas de sobrevida. RESULTADOS: Entre os pacientes, a FVC variou de 1,86% a 29,9%, mediana 6,19%; nos corações normais, de 0,13% a 1,46%, mediana 0,36% (p<0,0001 entre CMH e controle). Não foram observadas correlações significativas entre FVC e medidas ecocardiográficas basais. Pacientes com FVC<6,19% e FVC>6,19% foram comparados e não foram observadas diferenças basais. Entretanto, após um período de seguimento médio de 110 meses, quatro mortes ocorreram (duas súbitas, duas por insuficiência cardíaca) no grupo com FVC maior, enquanto os pacientes do grupo com FVC menor estavam vivos ao final do período (p=0,02). CONCLUSÃO: Pela primeira vez, a fibrose miocárdica foi prospectivamente associada a um pior prognóstico em pacientes com CMH. Esforços devem ser direcionados para quantificação da fibrose miocárdica na CMH, assumindo que a associação com o prognóstico pode auxiliar na estratificação de risco para implante de desfibrilador e na prescrição de fármacos potencialmente reparadores miocárdicos.

BACKGROUND: In hypertrophic cardiomyopathy (HCM), interstitial myocardial fibrosis is an important histological modification that has been associated with sudden death and evolution toward myocardial dilation. OBJECTIVE:To prospectively evaluate the prognostic value of the collagen volume fraction in HCM. METHODS: An endomyocardial biopsy of the right ventricle was successfully performed in 21 symptomatic patients with HCM. The myocardial collagen volume fraction (CVF) was determined by histology. The CVF was also determined in fragments of nine normal hearts from subjects deceased from non-cardiac causes. The patients were divided into above-median CVF and below-median CVF groups, and their clinical and echocardiographic characteristics and survival curves were compared. RESULTS: Among the patients, the CVF ranged from 1.86% to 29.9%, median 6.19%; in normal hearts, from 0.13% to 1.46%, median 0.61%(p <0.0001 between HCM and control). There were no significant correlations between CVF and baseline echocardiographic measures. Patients with CVF < 6.19% and CVF> 6.19% were compared and no baseline differences were observed. However, after an average follow-up period of 110 months, four deaths occurred (two sudden, two due to heart failure) in the group with increased CVF, whereas the patients of the group with lower CVF were all alive at the end of the period (p = 0.02). CONCLUSION: For the first time, myocardial fibrosis was prospectively associated with a worse prognosis in patients with HCM. Efforts should be directed to the quantification of myocardial fibrosis in HCM, on the premise that its association with the prognosis can aid in the stratification of risk for defibrillator implantation, and in the prescription of drugs that potentially promote myocardial repair.

FUNDAMENTO: En la cardiomiopatía hipertrófica (CMH), la fibrosis miocárdica intersticial es una importante alteración histológica, que ha sido asociada con muerte súbita y evolución hacia dilatación. OBJETIVO:Evaluar, prospectivamente, el valor pronóstico de la fracción de colágeno en la CMH. MÉTODOS:Se realizó, con éxito, biopsia endomiocárdica del ventrículo derecho en 21 pacientes sintomáticos con CMH. La fracción de volumen de colágeno (FVC) miocárdico se determinó por medio de histología. Se determinó la FVC también en fragmentos de nueve corazones normales de individuos fallecidos por causas no cardiacas. Respecto a la FVC, se dividieron a los pacientes en grupos supra e inframedianos (FVC elevada y FVC baja, respectivamente), y se compararon las características clínicas y ecocardiográficas y las curvas de sobrevida. RESULTADOS: Entre los pacientes, la FVC tuvo variación del 1,86% al 29,9%, con mediana en el 6,19%. Ya en los corazones normales, del 0,13% al 1,46%, mediana en el 0,36% (p<0,0001 entre CMH y control). No se verificaron correlaciones significativas entre FVC y medidas ecocardiográficas basales. Se compararon a pacientes con FVC<6,19 por ciento y FVC>6,19%, sin que se observara diferencias basales. Sin embargo, tras un período de seguimiento promedio de 110 meses, cuatro muertes ocurrieron (dos súbitas, y otras dos por insuficiencia cardiaca) en el grupo con FVC mayor, mientras que los pacientes del grupo con FVC menor estaban vivos al final del período (p=0,02). CONCLUSIÓN: Por primera vez, se asoció prospectivamente la fibrosis miocárdica a un peor diagnóstico en pacientes con CMH. Se deben encaminar esfuerzos hacia la cuantificación de la fibrosis en la CMH, al aceptar que la asociación con el pronóstico puede auxiliar tanto en la estratificación de riesgo para implante de desfibrilador, como en la prescripción de fármacos potencialmente reparadores...

Disfunção ventricular esquerda em hamsters com doença de Chagas tratados com etanercept / Left ventricular dysfunction in hamsters with Chagas disease and treated with etanercept

Objetivo: a doença afeta mais de 10 milhões de pessoas na América Latina. Leva a cardiomiopatia dilatada inflamatória em 30% dos pacientes como conseqüência tardia da infecção pelo protozoário Trypanosoma cruzi, com pior prognóstico que as outras cardiomiopatias dilatadas. estudos prévios mostram aumento dos níveis circulantes do fator de necrose tumoral-alfa (TNF-x) em pacientes com cardiomiopatia chagásica crônica. Assim, o objetivo do presente trabalho foi avaliar efeito do bloqueio do TNF-x com Etanercept na função ventricular esquerda em hamsters sírios cronicamente infectados pelo T. cruzi...

Aldosterone antagonism in an inflammatory state: evidence for myocardial protection.

INTRODUCTION: Chagas' disease is one of the most important causes of dilated cardiomyopathy in South and Central America. It is an inflammatory cardiomyopathy. We wanted to investigate whether it could have the same response to aldosterone antagonism as demonstrated before in other dilated cardiomyopathies. OBJECTIVE: To evaluate the role of spironolactone in myocardial remodelling in a Chagas cardiomyopathy model. MATERIAL AND METHODS: We studied 60 Sirius Hamsters divided into: control (C) infected (Inf) and Inf plus spironolactone (Infsp, 40 mg/kg/day) groups, for 11 months. Echocardiography with colour doppler was performed. Left ventricular end diastolic diameter (LVEDD), fractional shortening (FS) and corrected isovolumic relaxation time (IRT) were evaluated, as well as interstitial collagen volume fraction (ICVF) and myocardial inflammation. RESULT: The results demonstrated that survival was improved by use of spironolactone in the chronic phase (p<0.04). Body weight (BW) was C:190 g, Inf:167 g*, Infsp:198 g (*p<0.05, compared to C and Infsp), LVEDD/BW was C:0.31, Inf: 0.35*, Infsp: 0.29 (*p<0.05, compared to C and Infsp), FS was C:38, Inf: 35.5, Infsp: 38 (with no statistical difference) and IRT was C: 23 msec, Inf: 26 msec*, Infsp: 22 msec (p<0.05, compared to C and Infsp). ICVF (%) was attenuated at LV (C: 0.34+/-0.1, Inf: 1.75+/-0.7*, Infsp: 0.95+/-0.2*; *p<0.05, p<0.05). CONCLUSION: Spironolactone attenuated the myocardial remodelling in Chagas cardiomyopathy, reduced mortality during the chronic phase and reduced inflammatory infiltration.