Is FGF-23 an early indicator of atherosclerosis and cardiac dysfunction in patients with gestational diabetes?

ABSTRACT Objective: Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone and plays a role in the pathogenesis of myocardial hypertrophy. The aim of this study was to evaluate the association of FGF-23 levels with echocardiographic parameters and insulin resistance (IR) in patients with gestational diabetes. Subjects and methods: Fifty-four pregnant patients with gestational diabetes mellitus (GDM) (age, 31.12 ± 5.72 years) and 33 healthy pregnant women (age, 29.51 ± 4.92 years) were involved in the study. Fasting insulin, fasting plasma glucose (FPG), lipid profile, oral glucose tolerance test (OGTT), FGF23, echocardiographic parameters, and carotid artery intima-media thickness (CIMT) were evaluated in the two groups. Results: The two groups were not significantly different in age, sex, body mass index, lipid profile, or blood pressure. Insulin, homeostatic model assessment-insulin resistance (HOMA-IR), FGF-23 levels, CIMT, left ventricular (LV) mass, LV mass index and myocardial performance index (MPI) were significantly higher in the GDM group. HOMA-IR was positively correlated with FGF-23, and insulin was positively correlated with FGF-23. Additionally, FGF-23 was positively correlated with CIMT, LV mass index, and MPI. Conclusion: Our findings suggest that monitoring serum FGF-23 may be useful as a non-invasive indicator of subclinical atherosclerosis in patients with GDM.

Adropin and Irisin in Patients with Cardiac Cachexia / Adropina e Irisina em Pacientes com Caquexia Cardíaca

Abstract Background: Cardiac cachexia is an important predictive factor of the reduction in survival of patients with heart failure with reduced ejection fraction. Objectives: The aims of the present study were to evaluate adropin and irisin levels in cachectic and non-cachectic subjects and the relationships between the levels of these proteins and clinical and laboratory parameters in patients with HFrEF. Methods: The clinical records of patients who were admitted to the cardiology outpatient clinic for heart failure with reduced ejection fraction were screened. Cachectic patients were identified and assigned to the study group (n = 44, mean age, 65.4 ± 11.2 y; 61.4% men). Heart failure with reduced ejection fraction patients without weight loss were enrolled as the control group (n = 42, mean age, 61.0 ± 16.5 y; 64.3% men). The serum adropin and irisin levels of all patients were measured. A p-value < 0.05 was considered significant. Results: Serum adropin and irisin levels were significantly higher in the cachexia group than in the controls (Adropin (ng/L); 286.1 (231.3-404.0) vs 213.7 (203.1-251.3); p < 0.001, Irisin (µg/mL); 2.6 (2.2-4.4) vs 2.1 (1.8-2.4); p = 0.001). Serum adropin and irisin levels were positively correlated with brain natriuretic peptide (BNP) levels and New York Heart Association (NYHA) class and negatively correlated with body mass index (BMI) and serum albumin levels (all p values: < 0.001). In a multivariate analysis, adropin was the only independent predictor of cachexia in the heart failure with reduced ejection fraction patients (OR: 1.021; 95% CI: 1.004−1.038; p = 0.017). Conclusions: The results suggest that adropin and irisin may be novel markers of cardiac cachexia in heart failure with reduced ejection fraction patients. Adropin and irisin are related with the severity of heart failure.

Resumo Fundamento: A caquexia cardíaca é um importante preditor de redução de sobrevida em pacientes com insuficiência cardíaca com fração de ejeção reduzida (ICFER). O objetivo deste estudo foi avaliar os níveis de adropina e irisina em pacientes com ICFER caquéticos e não caquéticos, assim como a relação entre os níveis dessas proteínas e os parâmetros clínicos e laboratoriais nesses pacientes. Objetivos: Os objetivos do presente estudo foram avaliar os níveis de adropina e irisina em indivíduos caquéticos e não caquéticos e as relações entre os níveis dessas proteínas e os parâmetros clínicos e laboratoriais em pacientes com ICFEN. Métodos: Os prontuários de pacientes atendidos no ambulatório de cardiologia para ICFER foram triados. Aqueles com ICFER caquéticos foram identificados e constituíram o grupo de estudo (n = 44; idade média, 65,4 ± 11,2 anos; 61,4% de homens). Aqueles com ICFER e sem perda de peso foram arrolados como grupo controle (n = 42; idade média, 61,0 ± 16,5 anos; 64,3% de homens). Os níveis séricos de adropina e irisina de todos os pacientes foram medidos. Considerou-se significativo um p-valor < 0,05. Resultados: Os níveis séricos de adropina e irisina foram significativamente mais altos nos pacientes caquéticos do que nos controles [adropina (ng/l): 286,1 (231,3-404,0) vs 213,7 (203,1-251,3); p < 0,001; irisina (µg/ml): 2,6 (2,2-4,4) vs 2,1 (1,8-2,4); p = 0,001]. Os níveis séricos de adropina e irisina correlacionaram-se positivamente com os níveis de peptídeo natriurético cerebral (BNP) e a classe funcional da New York Heart Association (NYHA), e negativamente com o índice de massa corporal (IMC) e os níveis séricos de albumina (todos os p-valores: < 0,001). Na análise multivariada, a adropina foi o único preditor independente de caquexia nos pacientes com ICFER (OR: 1,021; IC 95%: 1,004−1,038; p = 0,017). Conclusões: Os resultados sugerem que a adropina e a irisina possam ser novos marcadores de caquexia cardíaca em pacientes com ICFER. Adropina e irisina estão relacionadas com a gravidade da insuficiência cardíaca.

Natriuretic Peptide and Clinical Evaluation in the Diagnosis of Heart Failure Hemodynamic Profile: Comparison with Tissue Doppler Echocardiography / Peptídeo Natriurético e Avaliação Clínica no Diagnóstico do Perfil Hemodinâmico da Insuficiência Cardíaca: Comparação com Ecodopplercardiograma Tecidual

Abstract Background: Physical examination and B-type natriuretic peptide (BNP) have been used to estimate hemodynamics and tailor therapy of acute decompensated heart failure (ADHF) patients. However, correlation between these parameters and left ventricular filling pressures is controversial. Objective: This study was designed to evaluate the diagnostic accuracy of physical examination, chest radiography (CR) and BNP in estimating left atrial pressure (LAP) as assessed by tissue Doppler echocardiogram. Methods: Patients admitted with ADHF were prospectively assessed. Diagnostic characteristics of physical signs of heart failure, CR and BNP in predicting elevation (> 15 mm Hg) of LAP, alone or combined, were calculated. Spearman test was used to analyze the correlation between non-normal distribution variables. The level of significance was 5%. Results: Forty-three patients were included, with mean age of 69.9 ± 11.1years, left ventricular ejection fraction of 25 ± 8.0%, and BNP of 1057 ± 1024.21 pg/mL. Individually, all clinical, CR or BNP parameters had a poor performance in predicting LAP ≥ 15 mm Hg. A clinical score of congestion had the poorest performance [area under the receiver operating characteristic curve (AUC) 0.53], followed by clinical score + CR (AUC 0.60), clinical score + CR + BNP > 400 pg/mL (AUC 0.62), and clinical score + CR + BNP > 1000 pg/mL (AUC 0.66). Conclusion: Physical examination, CR and BNP had a poor performance in predicting a LAP ≥ 15 mm Hg. Using these parameters alone or in combination may lead to inaccurate estimation of hemodynamics.

Resumo Fundamento: Exame físico e peptídeo natriurético do tipo B (BNP) foram usados para estimar a hemodinâmica e adequar a terapia de pacientes com insuficiência cardíaca aguda descompensada (ICAD). Entretanto, correlação entre esses parâmetros e a pressão de enchimento do ventrículo esquerdo é controversa. Objetivo: Avaliar a acurácia diagnóstica do exame físico, da radiografia de tórax (RT) e do BNP para estimar a pressão atrial esquerda (PAE) avaliada pelo ecodopplercardiograma tecidual. Métodos: Pacientes admitidos com ICAD foram avaliados prospectivamente. As características diagnósticas dos sinais físicos de insuficiência cardíaca, RT e BNP para predizer elevação da PAE (> 15 mmHg), isolados ou combinados, foram calculadas. Teste de Spearman foi usado para analisar a correlação entre variáveis de distribuição não normal. O nível de significância foi 5%. Resultados: Este estudo incluiu 43 pacientes com idade média de 69,9 ± 11,1 anos, fração de ejeção ventricular esquerda de 25 ± 8.0%, e BNP de 1057 ± 1024,21 pg/mL. Individualmente, todos os parâmetros clínicos, RT e BNP apresentaram fraco desempenho para predizer PAE ≥ 15 mmHg. O escore clínico de congestão teve o pior desempenho [área sob a curva receiver operating characteristic (AUC) 0,53], seguindo-se escore clínico + RT (AUC 0,60), escore clínico + RT + BNP > 400 pg/mL (AUC 0,62) e escore clínico + RT + BNP > 1000 pg/mL (AUC 0,66). Conclusão: Exame físico, RT e BNP tiveram desempenho fraco para predizer PAE ≥15 mmHg. O uso desses parâmetros isoladamente ou em combinação pode levar a estimativa imprecisa do perfil hemodinâmico. (Arq Bras Cardiol. 2018; 110(3):270-277)

Endostatin a Potential Biomarker for Heart Failure with Preserved Ejection Fraction / Endostatina é um Potencial Biomarcador para a Insuficiência Cardíaca com Fração de Ejeção Preservada

Abstract Background: Endostatin is a circulating endogenous angiogenesis inhibitor preventing neovascularization. Previous studies demonstrated the prognostic value of Endostatin among patients with heart failure with reduced ejection fraction (HFrEF). However, the role of Endostatin among patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. Objective: This study aimed to investigate the association between serum Endostatin levels, natriuretic peptide levels and the severity of left ventricular diastolic dysfunction and the diagnosis of HFpEF. Methods: Endostatin serum concentrations were measured in 301 patients comprising 77 HFpEF patients, 169 patients with asymptomatic left ventricular diastolic dysfunction (ALVDD), and 55 controls with normal cardiac function. Results: Endostatin serum levels were significantly elevated in patients with HFpEF (median/interquartile range 179.0 [159-220]) and ALVDD (163.8 [145.4-191.3]) compared to controls (149.1 [130.6-176.9]), p < 0.001 and p = 0.004, respectively) and significant correlated with N-terminal pro B-type natriuretic peptide (NT-proBNP). Conclusions: This hypothesis-generating pilot study gives first evidence that Endostatin correlates with the severity of diastolic dysfunction and may become a novel biomarker for HFpEF. We hypothesize a rise in Endostatin levels may reflect inhibition of adaptive angiogenesis and adverse cardiac remodeling.

Resumo Fundamentos: A Endostatina é um inibidor circulante endógeno da angiogênese que previne a neovascularização. Estudos anteriores demonstraram o valor prognóstico da Endostatina em pacientes com insuficiência cardíaca com fracção de ejeção reduzida (ICFEr). No entanto, o papel da Endostatina entre os pacientes com insuficiência cardíaca com fração de ejeção preservada (ICFEp) permanece incerto. Objetivo: Investigar a associação entre os níveis séricos de Endostatina, níveis de peptídeos natriuréticos e a gravidade de disfunção ventricular esquerda e diastólica e o diagnóstico de ICFEp. Métodos: Mediu-se a concentração sérica de Endostatina em 301 pacientes, compreendendo 77 pacientes com ICFEp, 169 pacientes com disfunção ventricular esquerda assintomática diastólica (DVEAD) e 55 controles com a função cardíaca normal. Resultados: Os níveis de Endostatina no soro foram significativamente elevados em pacientes com ICFEp (mediana / intervalo interquartil 179,0 [159-220]) e DVEAD (163,8 [145,4-191,3]) em comparação com os controles (149,1 [130,6-176,9]), p < 0,001 e p = 0,004, respectivamente) e correlação significativa com o terminal do pro-peptídeo natriurético tipo B (NT-proBNP). Conclusões: Este estudo piloto gerador de hipótese fornece a primeira evidência de que a Endostatina se correlaciona com a gravidade da disfunção diastólica e pode tornar-se um novo biomarcador para ICFEp. Nossa hipótese é de que um aumento nos níveis de Endostatina pode refletir inibição da angiogênese adaptativa e remodelação cardíaca adversa.

Collaborative care model improves self-care ability, quality of life and cardiac function of patients with chronic heart failure

Chronic heart failure (CHF) is a common chronic disease that requires much care. This study aimed to explore the effects of collaborative care model (CCM) on patients with CHF. A total of 114 CHF patients were enrolled in this study, and were randomly and equally divided into two groups: control and experimental. Patients in the two groups received either usual care or CCM for 3 continuous months. The impacts of CCM on the self-care ability and quality of life were assessed using self-care of heart failure index and short form health survey 12, respectively. Further, cardiac function was assessed by measuring left ventricular ejection fraction (LVEF) and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), and by the 6-min walking test. Clinical and demographic characteristics of patients in the control and CCM groups were statistically equivalent. Compared with usual care, CCM significantly enhanced self-care abilities of patients with CHF, including self-care maintenance, self-care management and self-care confidence (all P<0.05). The physical and mental quality of life was also significantly improved by CCM (P<0.01 or P<0.05). Compared with usual care, CCM significantly increased the LVEF (P<0.01), decreased the NT-proBNP level (P<0.01), and enhanced exercise capacity (P<0.001). In conclusion, CCM improved the self-care, quality of life and cardiac function of patients with CHF compared with usual care.

Galectin-3: A Link between Myocardial and Arterial Stiffening in Patients with Acute Decompensated Heart Failure? / Galectina-3: Ligação entre Rigidez Miocárdica e Arterial em Pacientes com Insuficiência Cardíaca Descompensada?

Abstract Background: Heart failure is accompanied by abnormalities in ventricular-vascular interaction due to increased myocardial and arterial stiffness. Galectin-3 is a recently discovered biomarker that plays an important role in myocardial and vascular fibrosis and heart failure progression. Objectives: The aim of this study was to determine whether galectin-3 is correlated with arterial stiffening markers and impaired ventricular-arterial coupling in decompensated heart failure patients. Methods: A total of 79 inpatients with acute decompensated heart failure were evaluated. Serum galectin-3 was determined at baseline, and during admission, transthoracic echocardiography and measurements of vascular indices by Doppler ultrasonography were performed. Results: Elevated pulse wave velocity and low arterial carotid distensibility are associated with heart failure in patients with preserved ejection fraction (p = 0.04, p = 0.009). Pulse wave velocity, carotid distensibility and Young’s modulus did not correlate with serum galectin-3 levels. Conversely, raised galectin-3 levels correlated with an increased ventricular-arterial coupling ratio (Ea/Elv) p = 0.047, OR = 1.9, 95% CI (1.0‑3.6). Increased galectin-3 levels were associated with lower rates of left ventricular pressure rise in early systole (dp/dt) (p=0.018) and raised pulmonary artery pressure (p = 0.046). High galectin-3 levels (p = 0.038, HR = 3.07) and arterial pulmonary pressure (p = 0.007, HR = 1.06) were found to be independent risk factors for all-cause mortality and readmissions. Conclusions: This study showed no significant correlation between serum galectin-3 levels and arterial stiffening markers. Instead, high galectin-3 levels predicted impaired ventricular-arterial coupling. Galectin-3 may be predictive of raised pulmonary artery pressures. Elevated galectin-3 levels correlate with severe systolic dysfunction and together with pulmonary hypertension are independent markers of outcome.

Resumo Fundamento: A insuficiência cardíaca é acompanhada por anormalidades na interação ventrículo-vascular devido à rigidez miocárdica e arterial aumentada. A galectina-3 é um biomarcador recentemente descoberto que exerce um importante papel na fibrose miocárdica e vascular, e na progressão da insuficiência cardíaca. Objetivos: O objetivo deste estudo foi determinar se a galectina-3 está correlacionada com marcadores de rigidez arterial e acoplamento ventriculoarterial deficiente em pacientes com insuficiência cardíaca descompensada. Métodos: Um total de 79 pacientes internados com insuficiência cardíaca descompensada foi avaliado. Galectina-3 sérica basal foi determinada e, durante a admissão hospitalar, foram realizadas ecocardiografia transtorácica e medidas de índices vasculares por ultrassonografia Doppler. Resultados: Velocidade de onda de pulso elevada e baixa distensibilidade da artéria carótida estão associadas com insuficiência cardíaca em pacientes com fração de ejeção preservada (p = 0,04, p = 0,009). Velocidade de pulso, distensibilidade da artéria carótida e módulo de Young não se correlacionaram com níveis séricos de galectina-3. Por outro lado, níveis elevados de galectina-3 correlacionaram com razão de acoplamento ventriculoarterial aumentada (Ea/Elv) p = 0,047, OR = 1,9, IC 95% (1,0-3,6). Níveis aumentados de galectina-3 estavam associados com taxas mais baixas de pressão ventricular esquerda na fase inicial da sístole (dp/dt) (p = 0,018), e pressão arterial pulmonar aumentada (p = 0,046). Os resultados mostraram que níveis elevados de galectina-3 (p = 0,038, HR = 3,07) e pressão pulmonar arterial (p = 0,007, HR = 1,06) são fatores de risco independentes para mortalidade de todas as causas e reinternações hospitalares. Conclusões: O estudo mostrou que não houve correlação significativa entre níveis séricos de galectina-3 e marcadores de rigidez arterial. Altos níveis de galectina-3, por outro lado, foi um preditor de acoplamento ventriculoarterial deficiente. A galectina-3 pode ser um preditor de pressões arteriais pulmonares aumentadas. Níveis elevados de galectina-3 correlacionam-se com disfunção sistólica grave e, juntamente com hipertensão pulmonar, é um marcador independente de desfecho.

Copeptin in Hemodialysis Patients with Left Ventricular Dysfunction

PURPOSE: Copeptin has been considered as a useful marker for diagnosis and prediction of prognosis in heart diseases. However, copeptin has not been investigated sufficiently in hemodialysis patients. This study aimed to investigate the general features of copeptin in hemodialysis and to examine the usefulness of copeptin in hemodialysis patients with left ventricular dysfunction (LV dysfunction). MATERIALS AND METHODS: This study included 41 patients on regular hemodialysis. Routine laboratory data and peptides such as the N-terminal of the prohormone brain natriuretic peptide and copeptin were measured on the day of hemodialysis. Body fluid volume was estimated by bioimpedance spectroscopy, and the E/Ea ratio was estimated by echocardiography. RESULTS: Copeptin increased to 171.4 pg/mL before hemodialysis. The copeptin had a positive correlation with pre-dialysis body fluid volume (r=0.314; p=0.04). The copeptin level decreased along with body fluid volume and plasma osmolality during hemodialysis. The copeptin increased in the patients with LV dysfunction more than in those with normal LV function (218.7 pg/mL vs. 77.6 pg/mL; p=0.01). Receiver operating characteristic curve analysis showed that copeptin had a diagnostic value in the hemodialysis patients with LV dysfunction (area under curve 0.737; p=0.02) and that the cut-off value was 125.48 pg/mL (sensitivity 0.7, specificity 0.8, positive predictive value 0.9, negative predictive value 0.6). CONCLUSION: Copeptin increases in hemodialysis patients and is higher in patients with LV dysfunction. We believe that copeptin can be a useful marker for the diagnosis of LV dysfunction in hemodialysis patients.

Péptido natriurético tipo B en pacientes con enfermedad de Chagas: utilidad diagnóstica en la insuficiencia cardíaca / Natriuretic peptide in patients with Chagas disease: diagnostic utility in heart failure

La determinación de los niveles sanguíneos del péptido natriurético tipo B (BNP) ha demostrado ser de utilidad como marcadora de diagnóstico y pronóstico en la insuficiencia cardíaca congestiva. El objetivo del estudio fue cuantificar el BNP para conocer su asociación con el grado de disfunción sistólica en la enfermedad de Chagas. Se evaluaron 64 pacientes de la consulta de Chagas en la Unidad Cardiopulmonar del Hospital Universitario “Dr. Luis Razetti”, Barcelona, estado Anzoátegui, Venezuela, durante el periodo 2010-2011. Luego de la confirmación de la seropositividad a anticuerpos anti T. cruzi mediante tres pruebas inmunoserológicas (ELISA, inmunofluorescencia indirecta y hemaglutinación indirecta), los pacientes fueron clasificados en los Grupos I, II y III de la enfermedad cardíaca mediante la valoración del electrocardiograma, ecocardiograma y radiografía de tórax. En el estudio se incluyeron como controles a 33 pacientes cardiópatas seronegativos y a ocho voluntarios sanos. Los valores de BNP en los grupos fueron: Chagas I=18,87±18,00 pg/mL (n=20), Chagas II=99,88±171,52 pg/mL (n=24) y Chagas III=365,80±280,54 pg/mL (n=20). Se empleó como parámetro de referencia a la fracción de eyección del ventrículo izquierdo (FEVI <40%), los valores de sensibilidad y especificidad del BNP fueron 85,0% y 93,2% respectivamente (p< 0,0001; IC 95%), con un valor pronóstico del 89,0% (p=0,006). Estos resultados colocan al BNP en una posición equivalente a la del ecocardiograma para la evaluación de los pacientes cardiópatas, con las ventajas de simplicidad y rapidez de esta prueba bioquímica que la hace aplicable a estudios de campo en zonas endémicas de acceso limitado a los estudios ecocardiográficos.

The assessment of the type-B natriuretic peptide (BNP) has shown utility as a diagnostic and prognostic tool of heart failure. The aim of this study was to evaluate the BNP levels and to know its association within the systolic dysfunction level on Chagas disease. During the period 2010-2011, 64 patients were evaluated in the Chagas clinic of the Cardiopulmonary Unit of the University Hospital Dr. Luis Razetti, Barcelona- Anzoátegui state, Venezuela. After confirming the seropositive state to antibodies anti-T. cruzi with three inmunoserological tests (ELISA, indirect inmunofluorescence and indirect hemaglutination), patients were classified into Groups I, II and III of cardiac disease, by the evaluation with electrocardiogram, echocardiogram and thorax radiography. Thirty three seronegative cardiological patients and eight healthy volunteers were included in the study as controls. BNP groups levels were as follow: Chagas I = 18.87±18.00 pg/mL (n=20), Chagas II = 99.88±171.52 pg/mL (n=24) y Chagas III = 365.80±280.54 pg/mL (n=20). The sensitivity and specificity of BNP were 85.0% y 93.2%, respectively, (p< 0.0001; IC 95%), employing as parameter of reference the left ventricle fraction ejection (LVFE <40%), with a prognostic value of 89.0% (p=0.006). These results place the BNP in an equivalent position with the echocardiogram for the evaluation of cardiological patients, with the benefits of rapidity and simplicity, which makes the determination of this biochemical parameter a useful tool to perform field studies in endemic zones with limited access to the echocardiographic test.

Asociación entre marcadores bioquímicos y disfunción ventricular izquierda en infarto con elevación del segmento ST / Association between biochemical markers and left ventricular dysfunction in the ST-elevation acute myocardial infarction

Resumen Objetivo: La asociación entre marcadores serológicos y fracción de expulsión en el infarto no ha sido completamente estudiada. Nuestro objetivo es estudiar la asociación existente entre marcadores bioquímicos y disfunción ventricular izquierda en el infarto agudo de miocardio con elevación del segmento ST. Métodos: Con un diseño observacional, prospectivo, incluimos a pacientes con infarto con elevación ST en las primeras 24 h. Se analizaron al ingreso: recuento de leucocitos, glucemia, péptido natriurético tipo B y troponina T, y creatinfosfocinasa total y fracción MB al ingreso y en forma seriada. Estos parámetros se correlacionaron con la fracción de expulsión estimada por ecocardiograma. Resultados: Se incluyeron 108 pacientes. Mediana de fracción de expulsión 48% (intervalo intercuartílico 41-57). En el análisis de regresión lineal simple, el péptido natriurético tipo B (p = 0.005), el pico de creatinfosfocinasa fracción MB (p = 0.01), el recuento leucocitario (p = 0.001) y la glucemia (p = 0.033) se asociaron inversa y significativamente con la fracción de expulsión. No mostraron asociación los otros parámetros. En el análisis de regresión lineal múltiple, solo el péptido natriurético tipo B (p = 0.01) y el pico de creatinfosfocinasa fracción MB (p = 0.02) presentaron correlación significativa con la fracción de expulsión. Ambos parámetros se asociaron significativamente con una fracción de expulsión < 50%, de manera independiente a otras variables clínicas. Conclusiones: En la etapa aguda del infarto con elevación ST, el péptido natriurético tipo B y la creatinfosfocinasa fracción MB se asociaron significativamente con la disfunción ventricular izquierda independientemente de la presencia de otros marcadores bioquímicos y variables clínicas determinantes de disfunción ventricular.

Objective: The association between biochemical markers and left ventricular ejection fraction in patients with myocardial infarction was not completely studied. Our goal is to study the association between biochemical markers and left ventricular dysfunction in patients with ST-elevation acute myocardial infarction. Methods: With an observational and prospective design we included patients with less than 24 h ST-elevation myocardial infarction. Leukocytes, glucose, B-type natriuretic peptide and T troponin were measured at admission, and creatine-phosphokinase and creatine-phosphokinase-MB were measured at admission and serially, and correlated with the ejection fraction estimated by echocardiography. Results: A total of 108 patients were included. The median left ventricular ejection fraction was 48% (interquartile range 41-57). Simple linear regression analysis showed that B-type natriuretic peptide (P = .005), peak creatine-phosphokinase-MB (P = .01), leukocyte count (P = .001) and glucose (P = .033) were inversely and significantly associated with the left ventricular ejection fraction. The other parameters showed no association. B-type natriuretic peptide (P = .01) and peak creatine-phosphokinase-MB (P = .02) were the only two variables significantly associated with the left ventricular ejection fraction in the multiple linear regression analysis. Both markers were significantly associated with a left ventricular ejection fraction < 50%, independently of other clinical variables. Conclusion: B-type natriuretic peptide and peak creatine-phosphokinase-MB showed significant association with left ventricular ejection fraction in the acute phase of ST elevation acute myocardial infarction. This association was independent of the presence of other biochemical markers and clinical variables related to ventricular dysfunction.

Função diastólica na estenose aórtica: correlação com NT-ProBNP e remodelamento pós-operatório / Correlation to NT-ProBNP and remodeling after cardiac surgery

FUNDAMENTO: A função diastólica em portadores de estenose aórtica (EAO) é pouco estudada. Não é possível estabelecer uma possível correlação entre biomarcadores e disfunção diastólica. OBJETIVO: Avaliar a função diastólica em portadores de EAO submetidos à troca valvar através de ecocardiografia transtorácica e correlacionar com valores de NT-proBNP. MÉTODOS: Estudamos 31 pacientes com EAO (11 homens), com idade entre 21 e 81 anos (média de 61±15 anos), submetidos a tratamento cirúrgico de EAO. Foi realizada dosagem sérica de NT-proBNP e o resultado, comparado com variáveis ecocardiográficas obtidas pelo Doppler pulsado em fluxo mitral, Doppler pulsado em veias pulmonares e Doppler tecidual, tanto no pré quanto no pós-operatório. RESULTADOS: Observou-se melhora na Fração de Ejeção (FE) de AE e Tempo de Relaxamento Isovolumétrico (TRIV), além de redução nos seguintes parâmetros: a) Relação da velocidade diastólica precoce mitral (onda E) com a velocidade do anel mitral (onda E´) (E/E'), b) Volume sistólico de átrio esquerdo (AE), c) Volume sistólico de AE indexado, d) Diâmetro diastólico de ventrículo esquerdo (DDVE), e) Diâmetro sistólico de VE (DSVE), f) Volume diastólico final (VDF), g) Massa indexada de VE e h) Relação Volume/Massa de ventrículo esquerdo (VE). Os valores do NT-proBNP correlacionaram-se de modo positivo com os diversos graus de disfunção diastólica, tanto no pré como no pós-operatório. CONCLUSÃO: 1) A cirurgia de troca valvar para correção de EAO resultou em melhora significativa da função diastólica ventricular. 2) Os valores de NT-proBNP correlacionaram-se positivamente com as variáveis ecocardiográficas que determinam disfunção diastólica, sendo o NT-proBNP um bom marcador para caracterizar essa disfunção em portadores de EAO.

BACKGROUND: Few data are available on diastolic function in patients with aortic stenosis (AOS) with indication of surgical treatment. A potential correlation between biomarkers and diastolic function has not been established. OBJECTIVE: The aim of our study was to evaluate diastolic function in patients with AOS waiting for aortic valve replacement (AVR) echocardiographically, and to verify its correlation with serum brain natriuretic peptide (NT-proBNP). METHODS: Thirty-one AOS patients (11 male), 21 to 81 years old (mean age, 61±15 years old) were studied before and after AVR. Diastolic function was assessed with Doppler methods: transvalvar mitral flow, tissue Doppler imaging (TDI) and pulmonary venous Doppler (PVD), correlating with serum brain natriuretic peptide (NT-proBNP) before and 6 months after AVR. RESULTS: Comparing pre to post-operative period, we observed an increase of the left atrial ejection fraction and isovolumetric relaxation time (IRT), and the decrease of the mitral velocity to early diastolic velocity of the mitral annulus ratio (E/E'), the difference between the pulmonary A wave duration and mitral A duration, left atrial systolic volume, left atrial systolic volume index, left ventricular diastolic diameter, left ventricular systolic diameter, end diastolic volume (LVEDV), left ventricular mass index, left ventricular volume and mass index ratio. The values of NT-proBNP were positively correlated to diastolic dysfunction, both before and after surgery. CONCLUSION: AOS patients' ventricular diastolic function improved after AVR. The biomarker NT-proBNP might be a useful biomarker of diastolic function in these patients, before and after AVR. NT-proBNP values show a positive correlation with echocardiographic variables that determine diastolic dysfunction, and is a good marker for the characterization of this dysfunction in AOS patients.

Dessincronia ventricular e aumento dos níveis de BNP na estimulação apical do ventrículo direito / Ventricular dyssynchrony and increased BNP levels in right ventricular apical pacing / Disincronía ventricular y aumento de los niveles de BNP en la estimulación apical del ventrículo derecho

FUNDAMENTO: A estimulação apical crônica do ventrículo direito pode ocasionar dessincronia ventricular e, secundariamente, alterações neuro-humorais e aumento da morbimortalidade cardíaca. OBJETIVO: Pesquisar dessincronia ventricular e seus efeitos sobre os níveis de BNP em pacientes com marca-passo estimulados cronicamente no ápice do ventrículo direito (VD). MÉTODOS: Estudo transversal com 85 pacientes com marca-passo uni ou bicameral, em classe funcional I e II da NYHA e fração de ejeção do ventrículo esquerdo (FEVE) > 35 por cento. A avaliação de dessincronia foi realizada utilizando-se várias técnicas ecocardiográficas, incluindo o Tissue Synchronization Imaging (TSI), com análise dos 12 segmentos. O BNP foi dosado junto com o ecocardiograma, porém com o examinador cego. RESULTADOS: Quarenta e seis mulheres e 39 homens, com idade de 58 ± 12 anos, chagásicos (56 por cento) e hipertensos controlados (62 por cento), foram incluídos. A fração de ejeção do VE foi 52 ± 8 por cento e a duração média do QRS de 139 ms (120-180 ms). O BNP mostrou-se alterado em 36,5 por cento da amostra (ponto de corte de 60 pg/ml). Na análise multivariada de regressão linear, o BNP correlacionou-se com a idade (p = 0,024), FEVE (p < 0,0001) e tempo pré-ejetivo do VE (p = 0,009), que é índice de dessincronia intraventricular. CONCLUSÃO: Em pacientes com estimulação cardíaca convencional, estáveis clinicamente, a dessincronia intraventricular foi um preditor independente do aumento dos níveis de BNP, após ajuste pela idade e FEVE.

BACKGROUND: Long-term right ventricular apical pacing can cause ventricular dyssynchrony and, secondarily, neurohumoral alterations and increase in cardiac morbimortality. OBJECTIVE: To analyze ventricular dyssynchrony and its effects on BNP levels in patients with pacemakers and long-term right ventricular (RV) apex pacing. METHODS: Cross-sectional study of 85 patients with single or dual chamber pacemaker, NYHA functional class I or II and left ventricular ejection fraction (LVEF) > 35 percent. The dyssynchrony assessment was carried out using several echocardiographic techniques, including Tissue Synchronization Imaging (TSI), with the analysis of the 12 segments. BNP was measured at the same time when the echocardiogram was performed, but the examiner was blinded to the results. RESULTS: Forty-six women and 39 men, aged 58 ± 12 years, with Chagas' disease (56 percent) and controlled hypertensive individuals (62 percent), were included in the study. LVEF was 52 ± 8 percent and the mean QRS duration was 139 ms (120-180 ms). BNP levels were altered in 36.5 percent of the sample (cutoff = 60 pg/ml). At the multivariate linear regression analysis, BNP was correlated with age (p = 0.024), LVEF (p < 0.0001) and left ventricular (LV) pre-ejection time (p = 0.009), which is an intraventricular dyssynchrony index. CONCLUSION: In clinically stable patients receiving conventional cardiac pacing, the intraventricular dyssynchrony was an independent predictor of BNP level increase after adjusted for age and LVEF.

FUNDAMENTO: La estimulación apical crónica del ventrículo derecho puede ocasionar disincronía ventricular y, secundariamente, alteraciones neurohumorales y aumento de la morbimortalidad cardíaca. OBJETIVO: Investigar disincronía ventricular y sus efectos sobre los niveles de BNP en pacientes con marcapasos estimulados crónicamente en el ápice del ventrículo derecho (VD). MÉTODOS: Estudio transversal con 85 pacientes con marcapasos uni o bicameral, en clase funcional I y II de la NYHA y fracción de eyección del ventrículo izquierdo (FEVI) > 35 por ciento. La evaluación de disincronía fue realizada utilizando varias técnicas ecocardiográficas, incluyendo el Tissue Synchronization Imaging (TSI), con análisis de los 12 segmentos. El BNP fue dosado junto con el ecocardiograma, aunque con el examinador ciego. RESULTADOS: Cuarenta y seis mujeres y 39 hombres, con edad de 58 ± 12 años, chagásicos (56 por ciento) e hipertensos controlados (62 por ciento), fueron incluidos. La fracción de eyección del VI fue 52 ± 8 por ciento y la duración media del QRS de 139 ms (120-180 ms). El BNP se mostró alterado en 36,5 por ciento de la muestra (punto de corte de 60 pg/ml). En el análisis multivariado de regresión lineal, el BNP se correlacionó con la edad (p = 0,024), FEVI (p < 0,0001) y tiempo pre-eyectivo del VI (p = 0,009), que es índice de disincronía intraventricular. CONCLUSIÓN: En pacientes con estimulación cardíaca convencional, estables clínicamente, la disincronía intraventricular fue un predictor independiente del aumento de los niveles de BNP, después de ajuste por edad y FEVI.

Comparison of B-type natriuretic peptide and left ventricular dysfunction in patients with constrictive pericarditis undergoing pericardiectomy.

Chronic constrictive pericarditis (CCP) due to tuberculosis has high morbidity and mortality in the periopeartive period following pericardiectomy because of left ventricular (LV) dysfunction. Brain-type natriuretic peptide (BNP) is considered a marker for both LV systolic and diastolic dysfunction. We undertook this prospective study in 24 patients, to measure the BNP levels and to compare it with transmitral Doppler flow velocities, that is, the E/A ratio (E = initial peak velocity during early diastolic filling and A = late peak flow velocity during atrial systole), as a marker of diastolic function and systolic parameters, pre- and post-pericardiectomy, at the time of discharge. The latter parameters have been taken as a flow velocity across the mitral valve on a transthoracic echo. There was a significant decrease in the mean values of log BNP (6.19 ± 0.33 to 4.65 ± 0.14) (P = 0.001) and E/A ratio (1.81 ± 0.21 to 1.01 ± 0.14) (P = 0.001) post pericardiectomy, with a positive correlation, r = 0.896 and 0.837, respectively, between the two values at both the time periods. There was significant improvement in the systolic parameters of the LV function, that is, stroke volume index, cardiac index, systemic vascular resistance index, and delivered oxygen index. However, no correlation was observed between these values and the BNP levels. We believe that BNP can be used as a marker for LV diastolic dysfunction in place of the E/A ratio in patients with CCP, undergoing pericardiectomy. However, more studies have to be performed for validation of the same.

An equation to explain variations in blood NT-proBNP in ambulatory cardiac subjects.

BACKGROUND: NT-proBNP is being used as a biomarker for prognosticating and delineating cardiac dysfunction. The cut-off value for deciding normal versus abnormal levels has always been a point of contention since it depends on the degree of dysfunction as well as other associated conditions often termed non-cardiac factors and parameters. Such association had not been formally presented. OBJECTIVE: To determine the direction and magnitude of effect of cardiac and non-cardiac parameters on NT-proBNP variability. MATERIAL AND METHOD: The present study included 78 cardiac ambulatory patients with a history of heart failure and/or low left ventricular ejection fraction. Their cardiac and non-cardiac parameters were recorded at the time of blood sampling for NT-proBNP. Multivariate linear regression analysis was used to correlate cardiac and non-cardiac parameters with NT-proBNP level and, from this, a predictive equation was derived. RESULTS: Log [NT-proBNP (pmol/l)] was 1.424 + 0.348 (for EF of 18-27) + 0.636 (for EF < 18) + 0.021 CTR - 0.002 SMW- 0.326 for female + 0.430 Cr - 0.010 BW [EF = LV ejectionfraction in %; CTR = cardio-thoracic ratio in %; SMW = 6-minute walking distance in meters; Cr = serum creatinine in mg/dl; BW = body weight in kg]. The adjusted R-square for this regression was 0.659. Omitting the non-cardiac variables (sex, Cr, BW) would decrease the adjusted R-square to 0.493. CONCLUSION: Cut-off value for NT-proBNP concentration in subjects without severe systolic heart failure has to account for these non-cardiac factors.

Comparison of pro B-natriuretic peptide in hypertensive patients with and without diastolic dysfunction.

AIM: to evaluate whether pro BNP can be used for detection of diastolic dysfunction. METHODS: thirty nine hypertensive patients with normal systolic function, consecutively referred for echocardiography examination between October and December 2004 were recruited in the study. Diastolic dysfunction was diagnosed when echocardiographic mitral flow pattern demonstrated impaired relaxation, pseudonormalization or restrictive like patterns. NT-pro BNP levels were assessed using electro chemiluminescence Immunoassay (ECLIA) method. Unpaired t test was used to analyze the results. RESULTS: twelve out of thirty nine subjects had normal diastolic function. All base line characteristics, except for uric acid, were equally distributed between normal and abnormal diastolic function group. NT-pro BNP levels were nearly significantly higher in the diastolic dysfunction group (P=0.053). CONCLUSION: NT-pro BNP levels trends to be higher in hypertensive subjects with diastolic dysfunction.

Leptin levels in different forms of Chagas' disease

Leptin is produced primarily by adipocytes. Although originally associated with the central regulation of satiety and energy metabolism, increasing evidence indicates that leptin may be an important mediator in cardiovascular pathophysiology. The aim of the present study was to investigate plasma leptin levels in patient with Chagas' heart disease and their relation to different forms of the disease. We studied 52 chagasic patients and 30 controls matched for age and body mass index. All subjects underwent anthropometric, leptin and N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements and were evaluated by echocardiography, 12-lead electrocardiogram (ECG), and chest X-ray. All patients had fasting blood samples taken between 8:00 and 9:00 am. Chagasic patients were divided into 3 groups: group I (indeterminate form, IF group) consisted of 24 subjects with 2 positive serologic reactions for Chagas' disease and no cardiac involvement as evaluated by chest X-rays, ECG and two-dimensional echocardiography; group II (showing ECG abnormalities and normal left ventricular systolic function, ECG group) consisted of 14 patients; group III consisted of 14 patients with congestive heart failure (CHF group) and left ventricular dysfunction. Serum leptin levels were significantly lower (P < 0.001) in the CHF group (1.4 ± 0.8 ng/mL) when compared to the IF group (5.3 ± 5.3 ng/mL), ECG group (9.7 ± 10.7 ng/mL), and control group (8.1 ± 7.8 ng/mL). NT-proBNP levels were significantly higher (P < 0.001) in the CHF group (831.8 ± 800.1 pg/mL) when compared to the IF group (53.2 ± 33.3 pg/mL), ECG group (83.3 ± 57.4 pg/mL), and control group (32 ± 22.7 pg/mL). Patients with Chagas' disease and an advanced stage of CHF have high levels of NT-ProBNP andlow plasma levels of leptin. One or more leptin-suppressing mechanisms may operate in chagasic patients.

Relación entre hiperinsulinemia, disfunción diastólica e hipertrofia del ventrículo izquierdo en pacientes con hipertensión arterial sistémica / Association of hyperinsulinemia with left ventricular hypertrophy and diastolic dysfunction in patients with hypertension

Background: Hypertension is the main independent cardiovascular risk factor. However, there are additional factors that induce organic damage. Aim: To assess the association between hyperinsulinemia, ventricular hypertrophy and left ventricular diastolic function. Patients and Methods: Seventy-four patients aged 30 to 65 years, with mild or moderate systemic hypertension, with overweight or mild obesity and normal glucose tolerance curve (GTC), were studied. Serum insulin was measured during GTC. The maximum levels of insulin and glucose were observed 60 minutes after the oral glucose load and they were expressed as rG/1. Patients were stratified in three groups according to their glucose and insulin fasting levels (I0) and post-glucose challenge levels (rG/I): Group 1 (normoinsulinemic patients) I0 <17 mU/mL and rG/I >2 (2.45+0.4). Group 2 (post-prandial hyperinsulinemic patients) I0 <17 mU/mL and rG/I <2> 1 (1.34+0.3). Group 3 (persistently hyperinsulinemic patients) I0 >17 mU/mL and <1 (0.7+0.3). Left ventricular mass and its diastolic function were measured by Doppler echocardiography. Results: No differences in blood pressure or age were observed between groups. There was a negative correlation between ventricular mass and rG/1 (r =-0.282, p =0.015). Left ventricular diastolic dysfunction was significantly more deteriorated in group 3, as compared with group 1 (p <0.001 ANOVA). There was a significant correlation between g/GI and diastolic dysfunction (r =0.232 p =0.047). Conclusions: Fasting, post challenge hyperinsulinemia and a rG/I <1 are associated with higher ventricular mass and left ventricular diastolic dysfunction, independent of blood pressure and age.

B-natriuretic peptide level as a predictor for the severity of LV dysfunction

B -Natriuretic peptide is a neurohormone normally synthesized in ventricular heart muscle and known to be released in situations when left ventricular wall stress increases, it has a variety of physiological functions on its own, that are thought to be compensatory. The aim of this study was to apply B-natriuretic peptide [BNP] as a biomarker and to correlate its levels with the severity of heart failure using certain selected parameters as indicators of cardiac function. Forty Six [46] patients with provisional diagnosis of heart failure were chosen for this work, thirty six [36] males and ten [10] females, their age ranged between 33 and 80 years. All underwent complete physical examination and ECG tracing together with ECHO/DOPPLER examination for heart failure. Eleven [11] healthy subjects were chosen as control group for purpose of comparison. The patients were divided into groups, according to Age, Gender, BMI whether they had the following selected associated diseases: [IHD, hypertension, and diabetes mellitus], smoking habit. Drugs intake, cardiac chambers dilatation including [LV in systole and diastole, RV, and LA], EF%, FS%, degree of diastolic impairment, LV Segmental wall motion abnormalities. Five ml [5ml] specimen of venous blood were aspirated from each patient, and also the control group for estimation of BNP level using ELIZA technique. There was a significant difference in mean serum BNP levels between cases of congestive heart failure and control group. Considering the subject as a positive for heart failure if his BNP level was >/= 375pmol/l, at this cutoff value there will be a sensitivity of 80.4% and specificity of 100%. Also the study showed highest values of mean BNP in those patients having restrictive pattern of diastolic dysfunction. BNP was used as a biomarker for the first time in Iraq to diagnose congestive heart failure. The role of BNP as a guide to determine the severity of heart failure and the efficacy of treatment was promising, so BNP fulfill most of the criteria in patients with suspected heart failure. At this point it was found that the mean of the right ventricular dimensions were significantly higher in the group with highest BNP quartile compared to lowest quartile BNP group, probably reflecting more severe form of impaired cardiac function and heart failure, a finding which has not been mentioned in any earlier studies in the same field

Pressure and time dependence of the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15 and -40 mmHg, we observed a similar response in both groups at the 1st min, but a marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P = 0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as another neurohumoral measurement of cardiopulmonary receptor response to LBNP, and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P = 0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy is blunted at lower levels of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal initial response that decreases progressively with time. As a consequence of the time-dependent response, the cardiopulmonary reflex response should be measured over small intervals of time in clinical studies.