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Evidence suggests that myocardial interstitial fibrosis, resulting from cardiac remodeling, may possibly be influenced by mechanisms activated through the inhalation of airborne pollutants. However, limited studies have explored the relationship between lifetime exposure to carbon-based particles and cardiac fibrosis, specially using post-mortem samples. This study examined whether long-term exposure to air pollution (estimated by black carbon accumulated in the lungs) is associated with myocardial fibrosis in urban dwellers of megacity of Sao Paulo. Data collection included epidemiological and autopsy-based approaches. Information was obtained by interviewing the next of kin and through the pathologist's report. The individual index of exposure to carbon-based particles, which we designed as the fraction of black carbon (FBC), was estimated through quantification of particles on the macroscopic lung surface. Myocardium samples were collected for histopathological analysis to evaluate the fraction of cardiac fibrosis. The association between cardiac fibrosis and FBC, age, sex, smoking status and hypertension was assessed by means of multiple linear regression models. Our study demonstrated that the association of FBC with cardiac fibrosis is influenced by smoking status and hypertension. Among hypertensive individuals, the cardiac fibrosis fraction tended to increase with the increase of the FBC in both groups of smokers and non-smokers. In non-hypertensive individuals, the association between cardiac fibrosis fraction and FBC was observed primarily in smokers. Long-term exposure to tobacco smoke and environmental particles may contribute to the cardiac remodeling response in individuals with pre-existing hypertension. This highlights the importance of considering hypertension as an additional risk factor for the health effects of air pollution on the cardiovascular system. Moreover, the study endorses the role of autopsy to investigate the effects of urban environment and personal habits in determining human disease.
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Contaminantes Atmosféricos , Contaminación del Aire , Hipertensión , Humanos , Contaminantes Atmosféricos/análisis , Brasil , Remodelación Ventricular , Pulmón , Fibrosis , Carbono/análisisRESUMEN
BACKGROUND/OBJECTIVES: Myocardial infarction (MI) frequently leads to cardiac remodeling and failure with impaired life quality, playing an important role in cardiovascular deaths. Although physical exercise is a well-recognized effective non-pharmacological therapy for cardiovascular diseases, the effects of strength training (ST) on the structural and functional aspects of cardiac remodeling need to be further documented. In this study, we aimed to investigate the role of a linear block ST protocol in the rat model of MI. METHODS AND RESULTS: After 6 weeks of MI induction or sham surgery, male adult rats performed ST for the following 12 weeks. The ladder-based ST program was organized in three mesocycles of 4 weeks, with one load increment for each block according to the maximal carrying load test. After 12 weeks, the infarcted-trained rats exhibited an increase in performance, associated with reduced cardiac hypertrophy and pulmonary congestion compared with the untrained group. Despite not changing MI size, the ST program partially prevented cardiac dilatation and ventricular dysfunction assessed by echocardiography and hemodynamics, and interstitial fibrosis evaluated by histology. In addition, isolated cardiac muscles from infarcted-trained rats had improved contractility parameters in a steady state, and in response to calcium or stimuli pauses. CONCLUSIONS: The ST in infarcted rats increased the capacity to carry mass, associated with attenuation of cardiac remodeling and pulmonary congestion with improving cardiac function that could be attributed, at least in part, to the improvement of myocardial contractility.
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Insuficiencia Cardíaca , Infarto del Miocardio , Entrenamiento de Fuerza , Humanos , Ratas , Masculino , Animales , Entrenamiento de Fuerza/métodos , Remodelación Ventricular , Ratas Wistar , Insuficiencia Cardíaca/tratamiento farmacológico , Miocardio/patología , Infarto del Miocardio/tratamiento farmacológico , Cardiomegalia , ColágenoRESUMEN
BACKGROUND: Sudden cardiac death (SCD) can be the first clinical event of Chagas heart disease (CHD). However, current guidelines contain no clear recommendation for early cardioverter-defibrillator implantation. Using imaging modalities, we evaluated associations among autonomic denervation, myocardial hypoperfusion, fibrosis and ventricular arrhythmia in CHD. METHODS AND RESULTS: Twenty-nine patients with CHD and preserved left ventricular function underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy, 99mTc-methoxyisobutylisonitrile (MIBI) myocardial perfusion and cardiac magnetic resonance imaging (MRI). They were divided into arrhythmic (≥ 6 ventricular premature complexes/h and/or non-sustained ventricular tachycardia on 24-hour Holter, n = 15) and non-arrhythmic (< 6 ventricular premature complexes/h and no ventricular tachycardia; n = 14) groups. The arrhythmic group had higher denervation scores from MIBG imaging (23.2 ± 18.7 vs 5.6 ± 4.9; P < .01), hypoperfusion scores from MIBI SPECT (4.7 ± 6.8 vs 0.29 ± 0.6: P = .02), innervation/perfusion mismatch scores (18.5 ± 17.5 vs 5.4 ± 4.8; P = .01) and fibrosis by late gadolinium enhancement on MRI (14.3% ± 13.5% vs 4.0% ± 2.9%; P = .04) than the non-arrhythmic group. CONCLUSION: These imaging parameters were associated with ventricular arrhythmia in early CHD and may enable risk stratification and the implementation of primary preventive strategies for SCD.
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Cardiomiopatía Chagásica , Enfermedad de Chagas , Enfermedad de la Arteria Coronaria , Isquemia Miocárdica , Complejos Prematuros Ventriculares , Humanos , Cardiomiopatía Chagásica/complicaciones , Cardiomiopatía Chagásica/diagnóstico por imagen , 3-Yodobencilguanidina , Medios de Contraste , Gadolinio , Muerte Súbita Cardíaca/prevención & control , Fibrosis , Enfermedad de Chagas/complicaciones , Enfermedad de Chagas/diagnóstico por imagen , Desnervación AutonómicaRESUMEN
AIMS: The consumption of highly refined carbohydrates increases systemic inflammatory markers, but its potential to exert direct myocardial inflammation is uncertain. Herein, we addressed the impact of a high-refined carbohydrate (HC) diet on mice heart and local inflammation over time. MAIN METHODS: BALB/c mice were fed with a standard chow (control) or an isocaloric HC diet for 2, 4, or 8 weeks (HC groups), in which the morphometry of heart sections and contractile analyses by invasive catheterization and Langendorff-perfused hearts were assessed. Cytokines levels by ELISA, matrix metalloproteinase (MMP) activity by zymography, in situ reactive oxygen species (ROS) staining and lipid peroxidation-induced TBARS levels, were also determined. KEY FINDINGS: HC diet fed mice displayed left ventricular hypertrophy and interstitial fibrosis in all times analyzed, which was confirmed by echocardiographic analyses of 8HC group. Impaired contractility indices of HC groups were observed by left ventricular catheterization, whereas ex vivo and in vitro indices of contraction under isoprenaline-stimulation were higher in HC-fed mice compared with controls. Peak levels of TNF-α, TGF-ß, ROS, TBARS, and MMP-2 occur independently of HC diet time. However, a long-lasting local reduction of the anti-inflammatory cytokine IL-10 was found, which was linearly correlated to the decline of systolic function in vivo. SIGNIFICANCE: Altogether, the results indicate that short-term consumption of HC diet negatively impacts the balance of anti-inflammatory defenses and proinflammatory/profibrotic mediators in the heart, which can contribute to HC diet-induced morphofunctional cardiac alterations.
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Tejido Adiposo , Citocinas , Animales , Ratones , Carbohidratos de la Dieta , Especies Reactivas de Oxígeno , Sustancias Reactivas al Ácido Tiobarbitúrico , Dieta , InflamaciónRESUMEN
Background: Chagas disease is characterized by intense myocardial fibrosis stimulated by the exacerbated production of inflammatory cytokines, oxidative stress, and apoptosis. Air pollution is a serious public health problem and also follows this same path. Therefore, air pollution might amplify the inflammatory response of Chagas disease and increase myocardial fibrosis. Methods: We studied groups of Trypanosoma cruzi infected Sirius hamsters (Chagas=CH and Chagas exposed to pollution=CH+P) and 2 control groups (control healthy animals=CT and control exposed to pollution=CT+P). We evaluated acute phase (60 days post infection) and chronic phase (10 months). Echocardiograms were performed to assess left ventricular systolic and diastolic diameter, in addition to ejection fraction. Interstitial collagen was measured by morphometry in picrosirius red staining tissue. The evaluation of inflammation was performed by gene and protein expression of cytokines IL10, IFN-γ, and TNF; oxidative stress was quantified by gene expression of NOX1, MnSOD, and iNOS and by analysis of reactive oxygen species; and apoptosis was performed by gene expression of BCL2 and Capsase3, in addition to TUNEL analysis. Results: Chagas groups had increased collagen deposition mainly in the acute phase, but air pollution did not increase this deposition. Also, Chagas groups had lower ejection fraction in the acute phase (p = 0.002) and again air pollution did not worsen ventricular function or dilation. The analysis of the inflammation and oxidative stress pathways were also not amplified by air pollution. Apoptosis analysis showed increased expression of BCL2 and Caspase3 genes in chagasic groups in the acute phase, with a marginal p of 0.054 in BCL2 expression among infected groups, and TUNEL technique showed amplified of apoptotic cells by pollution among infected groups. Conclusions: A possible modulation of the apoptotic pathway was observed, inferring interference from air pollution in this pathway. However, it was not enough to promote a greater collagen deposition, or worsening ventricular function or dilation caused by air pollution in this model of Chagas cardiomyopathy.
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Contaminación del Aire , Cardiomiopatía Chagásica , Enfermedad de Chagas , Trypanosoma cruzi , Animales , Colágeno , Cricetinae , Citocinas , Fibrosis , Inflamación , Modelos Teóricos , Proteínas Proto-Oncogénicas c-bcl-2 , Remodelación VentricularRESUMEN
Clinical trials have shown that sodium glucose co-transporter 2 (SGLT2) inhibitors improve clinical outcomes in diabetes mellitus (DM) patients. As most studies were performed in Type 2 DM, the cardiovascular effects of SGLT2 inhibition still require clarification in Type 1 DM. We analyzed the effects of SGLT2 inhibitor dapagliflozin on cardiac remodeling in rats with streptozotocin-induced diabetes, an experimental model of Type 1 DM. Methods: Male Wistar rats were assigned into four groups: control (C, n = 14); control treated with dapagliflozin (C + DAPA, n = 14); diabetes (DM, n = 20); and diabetes treated with dapagliflozin (DM + DAPA, n = 20) for 8 weeks. Dapagliflozin dosage was 5 mg/kg/day. Statistical analyses: ANOVA and Tukey or Kruskal−Wallis and Dunn. Results: DM + DAPA presented decreased blood pressure and glycemia and increased body weight compared to DM (C 507 ± 52; C + DAPA 474 ± 50; DM 381 ± 52 *; DM + DAPA 430 ± 48 # g; * p < 0.05 vs. C; # p < 0.05 vs. C + DAPA and DM + DAPA). DM echocardiogram presented left ventricular and left atrium dilation with impaired systolic and diastolic function. Cardiac changes were attenuated by dapagliflozin. Myocardial hydroxyproline concentration and interstitial collagen fraction did not differ between groups. The expression of Type III collagen was lower in DM and DM + DAPA than their controls. Type I collagen expression and Type I-to-III collagen ratio were lower in DM + DAPA than C + DAPA. DM + DAPA had lower lipid hydroperoxide concentration (C 275 ± 42; C + DAPA 299 ± 50; DM 385 ± 54 *; DM + DAPA 304 ± 40 # nmol/g tissue; * p < 0.05 vs. C; # p < 0.05 vs. DM) and higher superoxide dismutase and glutathione peroxidase activity than DM. Advanced glycation end products did not differ between groups. Conclusion: Dapagliflozin is safe, increases body weight, decreases glycemia and oxidative stress, and attenuates cardiac remodeling in an experimental rat model of Type 1 diabetes mellitus.
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Resumo Fundamento: Na cardiomiopatia chagásica crônica (CCC), impõem-se estudos com a proposta de identificar fatores de risco arritmogênicos em pacientes nos quais a disfunção ventricular de moderada a grave não está presente. Objetivos: Verificar a dependência entre arritmias ventriculares frequentes (ARV), fração de ejeção de ventrículo esquerdo (FEVE), extensão da fibrose pela ressonância magnética cardíaca (RMC) e dosagem de norepinefrina urinária (NOREPI) na CCC com FEVE preservada ou minimamente comprometida. Métodos: Foi analisada no Holter a presença de extrassístoles ventriculares >30/hora. Na RMC, avaliou-se a FEVE e a quantificação de massa fibrosada. Foi realizada a dosagem de NOREPI pelo método de Muskiet. A matriz de correlação foi calculada para aferir a capacidade de as variáveis preverem outra sendo considerado significante p<0,05. Resultados: Foram incluídos no estudo 59 pacientes, com idade média de 57,9±10,94 anos. Arritmia ventricular frequente (ARV) foi detectada em 28 pacientes. A variável fibrose mostrou-se inversamente proporcional à fração de ejeção de ventrículo esquerdo (FEVE) (R de −0,61) e à norepinefrina urinária (NOREPI) (R de −0,68), assim como a variável ARV mostrou-se inversamente proporcional à FEVE (R de −0,33) e à NOREPI (R de −0,27). Já a FEVE mostrou-se diretamente proporcional à NOREPI (R de 0,83). Conclusão: Nesta amostra, em pacientes com CCC com FEVE preservada ou discretamente reduzida, observa-se a integridade do sistema nervoso autonômico em corações com pouca fibrose e FEVE mais elevada, apesar da presença de tradicionais fatores de risco para morte súbita cardíaca. Há dependência entre os níveis de NOREPI, FEVE e fibrose miocárdica, mas não com ARV.
Abstract Background: In Chronic Chagas Cardiomyopathy (CCC), studies are needed to identify arrhythmogenic risk factors in patients in which moderate to severe ventricular dysfunction is not present. Objective: To verify the correlation between frequent ventricular arrhythmias (PVC), left ventricular ejection fraction (LVEF), extension of fibrosis by cardiac magnetic resonance (CMR), and urinary norepinephrine measurement (NOREPI) in CCC with preserved or mildly compromised LVEF. Methods: The presence of ventricular extrasystoles > 30/h was analyzed on Holter. At CMR, LVEF and quantification of fibrosis mass were evaluated. The dosage of NOREPI was performed using the Muskiet method. The correlation coefficient matrix was calculated to measure the predictive ability of the variables to predict another variable, with p < 0.05 being considered significant. Results: A total of 59 patients were included. The mean age was 57.9 + 10.94 years. PVC was detected in 28 patients. The fibrosis variable was inversely proportional to LVEF (R of −0.61) and NOREPI (R of −0.68). Also, the variable PVC was inversely proportional to LVEF (R of −0.33) and NOREPI (R of −0.27). On the other hand, LVEF was directly proportional to NOREPI (R of 0.83). Conclusion: In this sample, in patients with CCC with preserved or slightly reduced LVEF, integrity of the autonomic nervous system is observed in hearts with little fibrosis and higher LVEF despite the presence of traditional risk factors for sudden cardiac death. There is correlation between the levels of NOREPI, LVEF, and myocardial fibrosis, but not with PVC.
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Electrocardiographic (ECG) abnormalities are frequently identified in Chronic Chagas cardiomyopathy (CCC) patients and advanced abnormalities are related to a worse prognosis. Cardiac Magnetic Resonance (CMR) can precisely assess ventricular systolic dysfunction and quantify myocardial fibrosis (MF), both identified as prognostic factors. We sought to investigate if ECG abnormalities in CCC patients were associated with more severe myocardial involvement as evaluated by CMR. METHODS: CCC patients with 12lead ECG and CMR closely obtained were included. ECG analysis evaluated rhythm, presence, and type of intraventricular conduction disturbances (IVCD) and, ventricular premature beats (VPB). CMR short-axis cine and late gadolinium enhancement images were evaluated to obtain left and right ventricular ejection fractions and MF mass, respectively. Statistical significance was set in 5%. RESULTS: 194 CCC patients (98 women, 56 ± 14 years) were evaluated, and no IVCD was detected in 71. The most common IVCD was the association of right bundle branch block and left anterior fascicular block (RBBB+LAFB) in 58 patients, followed by isolated RBBB in 34, isolated LAFB in 17, and left bundle branch block (LBBB) in 14 patients. Of patients with no IVCD, 63% had MF and the burden of fibrosis (no IVCD - 7.4 ± 8.6%; RBBB - 6.6 ± 6.5%; p = 1.00), as well as left ventricular ejection fraction (LVEF) (no IVCD - 52 ± 14%; RBBB - 55 ± 10%; p = 1.00) were similar to patients with isolated RBBB. Left conduction system impairment was associated with lower LVEF (LAFB - 39 ± 15%; RBBB+LAFB- 41 ± 15%; and LBBB - 35 ± 15%; p < 0.001) and more MF (RBBB+LAFB - 12.2 ± 10.4%; LBBB - 10.6 ± 7.5%; and LAFB - 12.0 ± 7.0%; p < 0.001). The univariable model showed that the presence of MF was related to RBBB+LAFB (OR 5.0; p = 0.001) and VPB (OR 6.3; p = 0.014). After adjustment for age, gender, and different risk factors in a multivariable model, the same findings were still significantly related to CMR myocardial fibrosis (RBBB+LAFB OR 5.0; p = 0.002 / VPB OR 6.9; p = 0.015). CONCLUSIONS: ECG without IVCD does not exclude serious cardiac abnormalities in CCC, and isolated RBBB seems to have a benign course. The presence of VPB and left branch conduction impairment, especially LAFB associated with RBBB, indicate a more severe cardiac involvement.
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Cardiomiopatías , Cardiomiopatía Chagásica , Enfermedad de Chagas , Disfunción Ventricular Izquierda , Arritmias Cardíacas/complicaciones , Bloqueo de Rama , Cardiomiopatías/complicaciones , Cardiomiopatía Chagásica/complicaciones , Cardiomiopatía Chagásica/diagnóstico por imagen , Enfermedad de Chagas/complicaciones , Cicatriz/complicaciones , Medios de Contraste , Electrocardiografía , Femenino , Gadolinio , Humanos , Imagen por Resonancia Magnética , Volumen Sistólico , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/etiología , Función Ventricular IzquierdaRESUMEN
ABSTRACT Background: We aimed to describe the morphology of the border zone of viable myocardium surrounded by scarring in patients with Chagas heart disease and study their association with clinical events. Methods: Adult patients with Chagas heart disease (n=22; 55% females; 65.5 years, SD 10.1) were included. Patients underwent high-resolution contrast-enhanced cardiac magnetic resonance using myocardial delayed enhancement with postprocessing analysis to identify the core scar area and border zone channels number, mass, and length. The association between border zone channel parameters and the combined end-point (cardiovascular mortality or internal cardiac defibrillator implantation) was tested by multivariable Cox proportional hazard regression analyses. The significance level was set at 0.05. Data are presented as the mean (standard deviation [SD]) or median (interquartile range). Results: A total of 44 border zone channels (1[1-3] per patient) were identified. The border zone channel mass per patient was 1.25 (0.48-4.39) g, and the extension in layers of the border zone channels per patient was 2.4 (1.0-4.25). Most border zone channels were identified in the midwall location. Six patients presented the studied end-point during a mean follow-up of 4.9 years (SD 1.6). Border zone channel extension in layers was associated with the studied end-point independent from left ventricular ejection fraction or fibrosis mass (HR=2.03; 95% CI 1.15-3.60). Conclusions: High-resolution contrast-enhanced cardiac magnetic resonance can identify border zone channels in patients with Chagas heart disease. Moreover, border zone channel extension was independently associated with clinical events.
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Bisphenol-A (BPA) is an endocrine disruptor associated with higher risk of insulin resistance, type 2 diabetes, and cardiovascular diseases especially in susceptible populations. Because malnutrition is a nutritional disorder associated with high cardiovascular risk, we sought to compare the effects of short-term BPA exposure on cardiovascular parameters of healthy and protein-malnourished mice. Postweaned male mice were fed a normo- (control) or low-protein (LP) diet for 8 weeks and then exposed or not to BPA (50 µg kg-1 day-1) for the last 9 days. Systolic blood pressure was higher in BPA or LP groups compared with the control group. However, diastolic blood pressure was enhanced by BPA only in malnourished mice. Left ventricle (LV) end diastolic pressure (EDP), collagen deposition, and CTGF mRNA expression were higher in the control or malnourished mice exposed to BPA than in the respective nonexposed groups. Nevertheless, mice fed LP diet exposed to BPA exhibited higher angiotensinogen and cardiac TGF-ß1 mRNA expression than mice treated with LP or BPA alone. Wall:lumen ratio and cross-sectional area of intramyocardial arteries were higher either in the LP or BPA group compared with the control mice. Taken together, our data suggest that short-term BPA exposure results in LV diastolic dysfunction and fibrosis, and intramyocardial arteries inward remodeling, besides potentiate protein malnutrition-induced hypertension and cardiovascular risk.
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INTRODUCTION: Few data exist regarding the late clinical impact of the Selvester score prediction of myocardial fibrosis after transcatheter aortic valve replacement (TAVR). This study evaluated the predictive power of the Selvester score on survival in patients with aortic stenosis (AS) undergoing TAVR. METHODS AND RESULTS: Patients with severe AS who had preoperative electrocardiograms were included. Clinical follow-up was obtained retrospectively. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular death and major adverse cardiac events (MACEs). Two-hundred twenty-eight patients were included (mean age, 81.5 ± 7.4 years; women, 58.3%). Deceased patients had a higher mean score (4.6 ± 3.2 vs. 1.4 ± 1.3; p < .001). At a mean follow-up of 36.2 ± 21.2 months, the Selvester score was independently associated with all-cause mortality (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.48-1.84; p < .001), cardiovascular death (HR, 1.59; 95% CI, 1.38-1.74; p < .001), and MACE (HR, 1.55; 95% CI, 1.30-1.68; p < .001). After 5 years, the mortality risk was incrementally related to the Selvester score. The involvement of the inferior wall of the left ventricle was a lower mortality risk factor (HR, 0.42; 95% CI, 0.18-0.98; p = .046). For a Selvester score of 3, the area under the curve showed 0.92, 0.94, and 0.86 (p < .001), respectively, for 1, 2, and 3 years. CONCLUSIONS: Elevated Selvester scores increase the risk of poor outcomes in patients with AS undergoing TAVR. The involvement of the anterior or lateral wall presents worse prognosis.
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Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Femenino , Humanos , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
Resumen La enfermedad de Chagas es un problema de salud pública en Latinoamérica, donde afecta a aproximadamente a 6 millones de personas. En Costa Rica se ha descrito la enfermedad desde 1941, con varios reportes de casos confirmados agudos y crónicos. La miocardiopatía chagásica afecta al 30% de los individuos con infección crónica y es la manifestación más grave de la enfermedad, con una morbimortalidad mayor que otras miocardiopatías. La resonancia magnética cardíaca, debido a su capacidad de caracterización tisular permite identificar con alta correlación histopatológica la presencia de fibrosis, edema e inflamación en la miocardiopatía chagásica. Esto ha permitido una mejor comprensión de la compleja fisiopatología de la enfermedad y además permite el diagnóstico diferencial con otras patologías simuladoras como lo es la cardiopatía isquémica. En la MCh la presencia de fibrosis miocárdica predice de manera independiente eventos adversos mayores tales como taquicardia ventricular sostenida y muerte cardiovascular. Debido a lo anterior la resonancia magnética cardíaca es una robusta herramienta capaz de mejorar el diagnóstico, la estratificación de riesgo y el pronóstico de estos pacientes, con miras a mejores y oportunas intervenciones terapéuticas.
Abstract Chagas disease is a public health problem in Latin America, where it affects approximately 6 million people. In Costa Rica the disease has been described since 1941, with several reports of acute and chronic confirmed cases. Chagas cardiomyopathy affects 30% of individuals with chronic infection and is the most serious manifestation of the disease, with a higher morbidity and mortality than other cardiomyopathies. Cardiac magnetic resonance, due to its capacity for tissue characterization, identifies the presence of fibrosis, aedema and inflammation in Chagas cardiomyopathy with high histopathological correlation. This has allowed a better understanding of the complex pathophysiology of the disease and also allows differential diagnosis with other pathologies that can simulate, such as ischemic heart disease. In Chagas cardiomyopathy, the presence of myocardial fibrosis independently predicts major adverse events such as sustained ventricular tachycardia and cardiovascular death. Due to the above, cardiac magnetic resonance is a robust tool capable of improving the diagnosis, risk stratification and prognosis of these patients, with a view to better and timely therapeutic interventions.
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Humanos , Espectroscopía de Resonancia Magnética/uso terapéutico , Cardiomiopatía Chagásica/diagnóstico por imagen , Enfermedad de Chagas/terapiaRESUMEN
Chronic Chagas' cardiomyopathy is the most severe and frequent manifestation of Chagas disease, and has a high social and economic burden. New imaging modalities, such as strain echocardiography, nuclear medicine, computed tomography and cardiac magnetic resonance imaging, may detect the presence of myocardial fibrosis, inflammation or sympathetic denervation, three conditions associated with risk of sudden death, providing additional diagnostic and/or prognostic information. Unfortunately, despite its high mortality, there is no clear recommendation for early cardioverter-defibrillator implantation in patients with Chagas heart disease in the current guidelines. Ideally, the risk of sudden cardiac death may be evaluated in earlier stages of the disease using new image methods to allow the implementation of primary preventive strategies.
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BACKGROUND: The relationship between microvasculopathy, autonomic denervation, and myocardial fibrosis, in Chagas cardiomyopathy is incompletely understood. The aim of this study was to explore the relative extent and anatomic distribution of myocardial hypoperfusion, autonomic denervation, and myocardial scarring using Single-Photon Emission Computerized Tomography (SPECT) imaging and Magnetic Resonance Imaging (MRI). METHODS: Thirteen patients with Chagas disease all had Iodine-123-metaiodobenzylguanidine (MIBG) SPECT, 99mTc-Sestamibi (MIBI) rest-stress SPECT, and gadolinium late enhancement MRI imaging within a 2-month interval. The anatomic location and extent of denervation, of stress-induced hypoperfusion and fibrosis, were assessed through image co-registration and quantification of abnormal tissue areas as a percent of total myocardium. RESULTS: The results showed a strong general anatomic concordance between areas of hypoperfusion, denervation, and fibrosis, suggesting that the three abnormal features may be correlated. Myocardial denervation was anatomically and quantitatively closely associated areas of stress hypoperfusion. CONCLUSION: Combined myocardial analysis of the extent and location of autonomic denervation, hypoperfusion, and scarring may allow for better understanding of the pathophysiology of Chagas cardiomyopathy. Autonomic myocardial denervation may be a more sensitive marker of cardiac involvement in Chagas Disease than finding by other imaging modalities.
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Desnervación Autonómica , Cardiomiopatía Chagásica/diagnóstico por imagen , Fibrosis/patología , Imagen por Resonancia Magnética/métodos , Microcirculación , Miocardio/patología , Tomografía Computarizada de Emisión de Fotón Único/métodos , 3-Yodobencilguanidina , Adulto , Anciano , Sistema Nervioso Autónomo/cirugía , Femenino , Corazón , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Persona de Mediana Edad , Imagen de Perfusión Miocárdica , Radiofármacos/farmacología , Factores de Riesgo , Tecnecio Tc 99m SestamibiRESUMEN
We evaluated the influence of aerobic training on cardiac remodeling in untreated spontaneously hypertensive rats (SHR). Four experimental groups were used: sedentary (W-SED, n=27) and trained (WEX, n=31) normotensive Wistar rats, and sedentary (SHR-SED, n=27) and exercised (SHR-EX, n=32) hypertensive rats. At 13 months old, trained groups underwent treadmill exercise five days a week for four months. Statistical analysis: ANOVA or Kruskal-Wallis. Exercised groups had higher physical capacity. Hypertensive groups presented left ventricular (LV) concentric hypertrophy with impaired function. Left atrium diameter, LV posterior wall thickness and relative thickness, and isovolumetric relaxation time were lower in SHR-EX than SHR-SED. Interstitial collagen fraction and Type I-Type III collagen ratio were higher in SHR-SED than W-SED. In SHR-EX these parameters had intermediate values between W-EX and SHRSED with no differences between either group. Myocardial matrix metalloproteinase-2 activity, evaluated by zymography, was higher in SHR-SED than W-SED and SHR-EX. TIMP-2 was higher in hypertensive than normotensive groups. In conclusion, low intensity aerobic exercise reduces left atrium dimension and LV posterior wall thickness, and improves functional capacity, diastolic function, and metalloproteinase-2 activity in adult SHR.
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Aorta/fisiopatología , Hipertensión/fisiopatología , Condicionamiento Físico Animal/fisiología , Remodelación Ventricular/fisiología , Animales , Aorta/metabolismo , Presión Sanguínea/fisiología , Corazón/fisiopatología , Hipertensión/metabolismo , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Miocardio/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas WistarRESUMEN
Chronic Chagas cardiomyopathy (CCC) is responsible for the disease's greater morbidity and poor prognosis. Although understanding the pathophysiology of CCC and the fundamentals of its clinical management derives from research related to other cardiomyopathies, there are peculiarities that distinguish CCC from the others. CCC is the most fibrous heart disease, and its myocardial involvement is important as it disorganizes or disrupts the extracellular matrix, creating an environment conducive to the formation of arrhythmogenic foci. It is also considered the most arrhythmogenic of the known heart diseases, giving rise to complex arrhythmias, usually associated with varying degrees of stimulus conduction disorders. The central proposal of this review is to describe a possible association between the distribution and degree of myocardial fibrosis and cardiac arrhythmogenicity in patients with Chagas cardiomyopathy, drawing attention to the importance of noninvasive biomarkers for the quantification of myocardial fibrosis.
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Cardiomiopatía Chagásica/patología , Miocardio/patología , Arritmias Cardíacas/patología , Biomarcadores/análisis , Cardiomiopatía Chagásica/fisiopatología , Enfermedad Crónica , Fibrosis , Humanos , NecrosisRESUMEN
BACKGROUND AND AIMS: Although many studies have reported the effects of AT1 receptor on dietary salt overload, the role of AT2 receptor in this model is far from completely elucidated. The present study aimed to better understand the role of AT2 receptor in cardiac structure alterations in response to chronic high salt intake in rats. METHODS AND RESULTS: Male Wistar rats were fed a normal or high salt diet from weaning until 18 weeks of age. Both groups were subdivided into two groups. Starting at 7 weeks of age, rats were treated with or without compound 21 (0.3 mg/kg/day, n = 16), an AT2 receptor agonist. Metabolics and structural parameters were measured. BP, transverse cardiomyocyte and intersticial fibrose was higher in animals fed with high salt diet compared with normal salt fed animals. CONCLUSION: Compound 21 prevented the development of cardiac hypertrophy and fibrosis, reduced the increase in blood pressure and prevented the lower weight gain in animals fed a high salt diet.
Asunto(s)
Cardiomegalia/prevención & control , Fármacos Cardiovasculares/farmacología , Miocitos Cardíacos/efectos de los fármacos , Receptor de Angiotensina Tipo 2/agonistas , Cloruro de Sodio Dietético , Sulfonamidas/farmacología , Tiofenos/farmacología , Remodelación Ventricular/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/metabolismo , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Modelos Animales de Enfermedad , Fibrosis , Hipertensión/metabolismo , Hipertensión/fisiopatología , Hipertensión/prevención & control , Masculino , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratas Wistar , Receptor de Angiotensina Tipo 2/metabolismo , Transducción de Señal , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND: Hypertrophic cardiomyopathy (HCM), a genetically transmitted disease, is the most common genetic cardiovascular disease. Current strategies to stratify risk are expensive and concentrated in wealthy centers. Twelve-lead electrocardiography (ECG) is inexpensive, universally available, and can be readily used for Selvester QRS scoring, which estimates scar size. This study aimed to establish the relation between ECG scar quantification and myocardial fibrosis (extent of myocardial delayed enhancement) in multidetector computed tomography (MDCT). HYPOTHESIS: There is a significant association between ECG scar quantification and the extent of myocardial delayed enhancement in MDCT. METHODS: Seventy-five patients with HCM underwent a routine clinical evaluation and echocardiography, 12-lead ECG, and MDCT study. Patients with and without an implantable cardioverter-defibrillator were included. RESULTS: The estimated Selvester QRS score of myocardial fibrosis was correlated significantly (R = 0.70; P < 0.01) with the quantified MDCT fibrosis. Compared with MDCT, the QRS score had 84.8% sensitivity and 88.8% specificity. Myocardial fibrosis was present in 88% of these patients with HCM (fibrotic mass, 9.87 ±10.8 g) comprising 5.66% ±6.16% of the total myocardial mass seen on the MDCT images. The Selvester QRS score reliably predicted the fibrotic mass in 76% of patients, which estimated 8.44% ±7.39% of the total myocardial mass. CONCLUSIONS: The Selvester QRS score provides reliable quantification of myocardial fibrosis and was well correlated with MDCT in patients with HCM.
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Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cicatriz/diagnóstico por imagen , Electrocardiografía , Tomografía Computarizada Multidetector , Miocardio/patología , Adulto , Cardiomiopatía Hipertrófica/patología , Cardiomiopatía Hipertrófica/fisiopatología , Cicatriz/patología , Cicatriz/fisiopatología , Femenino , Fibrosis , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: To investigate the correlation between the extent of myocardial sympathetic denervation and fibrosis and the presence of degrees of severity of ventricular arrhythmias in chronic Chagas cardiomyopathy (CCC). METHODS: Forty-three CCC patients with left ventricular ejection fraction (LVEF) ≥ 35% were divided into three groups: SVT group-presenting Sustained Ventricular Tachycardia (SVT) (n = 15), NSVT group-exhibiting episodes of non-SVT (NSVT) on 24-h Holter monitoring (n = 11), and Control group-exhibiting neither SVT nor episodes of NSVT (n = 17). The patients underwent SPECT imaging for myocardial sympathetic innervation with 123Iodine-MIBG (MIBG) and myocardial perfusion with 99mTc-Sestamibi (MIBI) for the evaluation of regional myocardial fibrosis. RESULTS: The summed rest perfusion scores were similar in the three groups. The summed difference score between MIBG and MPI images, which evaluated the extent of denervated but viable myocardium, was significantly higher in SVT group (20.0 ± 8.0) as compared with the control group (2.0 ± 5.0, P < .0001) and with the NSVT group (11.0 ± 8.0, P < .05). CONCLUSIONS: The occurrence of ventricular arrhythmias of different degrees of severity correlates quantitatively with the extent of cardiac sympathetic denervation, but not with the extent of fibrosis, suggesting that myocardial sympathetic denervation plays a major role in triggering ventricular arrhythmia in CCC.
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Arritmias Cardíacas/diagnóstico por imagen , Cardiomiopatía Chagásica/diagnóstico por imagen , Imagen de Perfusión Miocárdica , Simpatectomía , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Anciano , Ecocardiografía , Electrocardiografía , Femenino , Fibrosis , Corazón/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Miocardio/patología , Perfusión , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Sístole , Tecnecio Tc 99m SestamibiRESUMEN
BACKGROUND: In peripartum cardiomyopathy, the prevalence of focal myocardial damage detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance is important to elucidate mechanisms of myocardial injury and cardiac dysfunction. LGE equates irreversible myocardial injury, but LGE prevalence in peripartum cardiomyopathy is uncertain. METHODS AND RESULTS: Among 100 women enrolled within the Investigations of Pregnancy Associated Cardiomyopathy cohort, we recruited 40 women at 13 centers to undergo LGE cardiovascular magnetic resonance, enrolled within the first 13 weeks postpartum. Follow-up scans occurred at 6 months postpartum, and death/transplant rates at 12 months. Baseline characteristics did not differ significantly in the parent cohort according to cardiovascular magnetic resonance enrollment except for mechanical circulatory support. LGE was noted only in 2 women (5%) at baseline. While left ventricular dysfunction with enlargement was prevalent at baseline cardiovascular magnetic resonance scans (eg, ejection fraction 38% [Q1-Q3 31-50%], end diastolic volume index=108 mL/m2 [Q1-Q3 83-134 mL/m2]), most women demonstrated significant improvements at 6 months, consistent with a low prevalence of LGE. LGE was not related to baseline clinical variables, ejection fraction, New York Heart Association heart failure class, or mortality. Neither of the 2 women who died exhibited LGE. LGE was inversely associated with persistent left ventricular ejection fraction at 6 months (P=0.006). CONCLUSIONS: Factors other than focal myocardial damage detectable by LGE explain the initial transient depressions in baseline left ventricular ejection fraction, yet focal myocardial damage may contribute to persistent myocardial dysfunction and hinder recovery in a small minority. Most women exhibit favorable changes in ventricular function over 6 months. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01085955.