Muscarinic antibodies and heart rate responses to dynamic exercise and to the Valsalva maneuver in chronic chagasic patients / Anticorpos muscarínicos e resposta da frequência cardíaca ao exercício dinâmico e a manobra de Valsalva na doença de Chagas crônica

We have studied the cardiac chronotropic responses to the Valsalva maneuver and to dynamic exercise of twenty chronic chagasic patients with normal left ventricular function and no segmental wall abnormalities by two-dimensional echocardiogram. The absolute increase in heart rate of the patients (Δ = 21.5 ± 10 bpm, M±SD) during the maneuver was significantly diminished when compared to controls (Δ = 31.30 ± 70, M±SD, p = 0.03). The minimum heart rate (58.24 ± 8.90 vs. 62.80 ± 10, p = 0.68) and the absolute decrease in heart rate at the end of the maneuver (Δ = 38.30 ± 13 vs. Δ = 31.47 ± 17, p = 0.10) were not different from controls. The initial heart rate acceleration during dynamic exercise (Δ = 12 ± 7.55 vs. Δ = 19 ± 7.27, M±SD, p = 0.01) was also diminished, but the heart rate recovery during the first ten seconds was more prominent in the sero-positive patients (Median: 14, Interquartile range: (9.75-17.50 vs. 5(0-8.75, p = 0.001). The serum levels of muscarinic cardiac auto-antibodies were significantly higher in the chagasic patients (Median: 34.58, Interquartile Range: 17-46.5, Optical Density) than in controls (Median: 0, Interquartile Range: 0-22.25, p = 0.001) and correlated significantly and directly (r = 0.68, p = 0.002) with early heart rate recovery during dynamic exercise. The results of this investigation indirectly suggest that, the cardiac muscarinic auto-antibodies may have positive agonist effects on parasympathetic heart rate control of chagasic patients.

Foram estudadas as respostas cronotrópicas cardíacas à manobra de Valsalva e ao exercício dinâmico de vinte pacientes chagásicos com função ventricular esquerda normal e sem alterações da contractilidade segmentar por ecocardiografia bidimensional. O aumento absoluto da frequência cardíaca dos pacientes (Δ = 21,5 ± 10 bpm, M ± DP) durante a manobra de Valsalva foi significativamente menor quando se comparava ao grupo controle (Δ = 31,30 ± 70, p = 0,03). A frequência cardíaca mínima (58,24 ± 8,90 vs 62,80 ± 10, p = 0,68) e a diminuição da frequência cardíaca absoluta no final da manobra (Δ = 38,30 ± 13 vs Δ = 31,47 ± 17, p = 0,10) não foram diferentes em comparação com o grupo controle. A aceleração inicial da frequência cardíaca durante o exercício dinâmico (Δ = 12 ± 7,55 vs Δ = 19 ± 7,27, p = 0,01) também foi menor, mas a recuperação da frequência cardíaca, durante os primeiros dez segundos, foi maior no grupo sero-positivos [mediana:14 (intervalo interquartil: 9,75-17,50) vs 5 (0 - 8,75), p = 0,001]. Os níveis séricos de auto-anticorpos muscarínicos cardíacos foram significativamente maiores nos pacientes chagásicos do que no grupo controle [(mediana: 34,58 densidade óptica (intervalo interquartil 17 - 46,5) vs (mediana: 0, intervalo interquartil 0 - 22,25) p = 0,001] e a correlação é significativa e direta (r = 0,68, p = 0,002) com o início da recuperação da frequência cardíaca durante o exercício dinâmico. Os resultados desta investigação sugerem que indiretamente, os auto-anticorpos muscarínicos cardíacos, podem ter ação agonista positiva sobre o controle parassimpático da frequência cardíaca dos pacientes chagásicos.

Muscarinic antibodies and heart rate responses to dynamic exercise and to the Valsalva maneuver in chronic chagasic patients.

We have studied the cardiac chronotropic responses to the Valsalva maneuver and to dynamic exercise of twenty chronic chagasic patients with normal left ventricular function and no segmental wall abnormalities by two-dimensional echocardiogram. The absolute increase in heart rate of the patients (Δ = 21.5 ± 10 bpm, M±SD) during the maneuver was significantly diminished when compared to controls (Δ = 31.30 ± 70, M±SD, p = 0.03). The minimum heart rate (58.24 ± 8.90 vs. 62.80 ± 10, p = 0.68) and the absolute decrease in heart rate at the end of the maneuver (Δ = 38.30 ± 13 vs. Δ = 31.47 ± 17, p = 0.10) were not different from controls. The initial heart rate acceleration during dynamic exercise (Δ = 12 ± 7.55 vs. Δ = 19 ± 7.27, M±SD, p = 0.01) was also diminished, but the heart rate recovery during the first ten seconds was more prominent in the sero-positive patients (Median: 14, Interquartile range: (9.75-17.50 vs. 5(0-8.75, p = 0.001). The serum levels of muscarinic cardiac auto-antibodies were significantly higher in the chagasic patients (Median: 34.58, Interquartile Range: 17-46.5, Optical Density) than in controls (Median: 0, Interquartile Range: 0-22.25, p = 0.001) and correlated significantly and directly (r = 0.68, p = 0.002) with early heart rate recovery during dynamic exercise. The results of this investigation indirectly suggest that, the cardiac muscarinic auto-antibodies may have positive agonist effects on parasympathetic heart rate control of chagasic patients.

Hipertiroidismo subclínico exógeno: efecto en el sistema cardiovascular / Exogenous subclinical hyperthyroidism: Effect on the cardiovascular system

Objetivo: Evaluar los efectos del hipertiroidismo subclínico exógeno en la estructura y la función del ventrículo izquierdo. Material y método: Se estudió a 23 pacientes, de ambos sexos, de entre 27 y 70 años, con diagnóstico de hipertiroidismo subclínico exógeno (tirotropina [TSH] sérica, # 0,4 mU/ml, y tiroxina libre [T4l], normal) que habían recibido tratamiento con levotiroxina, a dosis supresora, durante un promedio de 6,7 (1-35) años. Se seleccionó a 20 sujetos con función tiroidea normal, ajustados por edad, sexo e índice de masa corporal, como controles. Se les realizó historia clínica y se cuantificaron las manifestaciones de hipertiroidismo. La estructura y la función del ventrículo izquierdo, así como el tiempo de conducción auricular, se evaluaron mediante un ecocardiograma bidimensional, un eco-Doppler pulsado y tisular con registro electrocardiográfico. Se calculó el índice de compensación hemodinámica de la masa del ventrículo izquierdo. Resultados: La puntuación de las manifestaciones de hipertiroidismo fue significativamente mayor (p = 0,0001) en los pacientes que en los controles. Se obtuvo una correlación positiva de la puntuación de hipertiroidismo con la T4l (p = 0,005) y la fracción de eyección (p = 0,04) y una correlación negativa con las concentraciones de TSH (p = 0,03). El volumen diastólico final, el volumen latido, el gasto cardíaco y el trabajo latido fueron significativamente más altos en los pacientes con hipertiroidismo subclínico (p = 0,04; p = 0,02; p = 0,05, y p = 0,01, respectivamente). Hubo una correlación positiva del acortamiento fraccional con la concentración de T4l (p = 0,022) y la dosis de levotiroxina (p = 0,016) y del trabajo latido con la concentración de T4l (p = 0,034). La masa del ventrículo izquierdo, la función diastólica y el tiempo de conducción auricular no fueron diferentes de los controles. Conclusiones: Nuestros resultados indican que en pacientes con hipertiroidismo subclínico exógeno se producen cambios hemodinámicos adaptativos al efecto biológico de la levotiroxina en el sistema cardiovascular, sin llegar a producirse cambios estructurales (AU)

Objective: To evaluate the effects of exogenous subclinical hyperthyroidism on left ventricular structure and function. Material and method: Twenty-three patients of both sexes, aged 27 to 70 years, with a diagnosis of exogenous subclinical hyperthyroidism (serum thyroid-stimulating hormone [TSH] # 0.4 mU/ml and normal free thyroxine [FT4]) were evaluated. The patients had been taking levothyroxine in suppressive doses for an average of 6.7 years (1 to 35 years). Twenty euthyroid individuals matched for age, sex and body mass index were selected as controls. A medical history was obtained and symptoms of thyrotoxicosis were quantified in all subjects. To evaluate left ventricular structure and function, as well as atrial conduction time, a two-dimensional echocardiogram and pulsed echo and tissue echo Doppler with electrocardiography monitoring were performed. The index of hemodynamic compensation of the left ventricular mass was calculated. Results: Hyperthyroid symptom scores were significantly higher in patients than in controls (p = 0.0001). A positive correlation was found between hyperthyroidism scores and FT4 (p = 0.005) and ejection fraction (p = 0.04) and a negative correlation was found with TSH levels (p = 0.03). End-diastolic volume, stroke volume, cardiac output and stroke work were significantly higher in patients with SH (p = 0.04, p = 0.02, p = 0.05 and p = 0.01, respectively). A positive correlation was found between fractional shortening and FT4 level (p = 0.022) and levothyroxine dose (p = 0.016) and between stroke work and FT4 level (p = 0.034). Left ventricular mass, diastolic function and atrial conduction time were similar in patients and controls. Conclusions: Our study suggests that patients with exogenous subclinical hyperthyroidism have hemodynamic changes resulting from adaptation to the biological effects of levothyroxine on the cardiovascular system. However, structural changes are not produced (AU)

Exogenous subclinical hyperthyroidism: effect on the cardiovascular system.

OBJECTIVE: To evaluate the effects of exogenous subclinical hyperthyroidism on left ventricular structure and function. MATERIAL AND METHOD: Twenty-three patients of both sexes, aged 27 to 70 years, with a diagnosis of exogenous subclinical hyperthyroidism (serum thyroid-stimulating hormone [TSH] ≤ 0.4mU/ml and normal free thyroxine [FT4]) were evaluated. The patients had been taking levothyroxine in suppressive doses for an average of 6.7 years (1 to 35 years). Twenty euthyroid individuals matched for age, sex and body mass index were selected as controls. A medical history was obtained and symptoms of thyrotoxicosis were quantified in all subjects. To evaluate left ventricular structure and function, as well as atrial conduction time, a two-dimensional echocardiogram and pulsed echo and tissue echo Doppler with electrocardiography monitoring were performed. The index of hemodynamic compensation of the left ventricular mass was calculated. RESULTS: Hyperthyroid symptom scores were significantly higher in patients than in controls (p=0.0001). A positive correlation was found between hyperthyroidism scores and FT4 (p=0.005) and ejection fraction (p=0.04) and a negative correlation was found with TSH levels (p=0.03). End-diastolic volume, stroke volume, cardiac output and stroke work were significantly higher in patients with SH (p=0.04, p=0.02, p=0.05 and p=0.01, respectively). A positive correlation was found between fractional shortening and FT4 level (p=0.022) and levothyroxine dose (p=0.016) and between stroke work and FT4 level (p=0.034). Left ventricular mass, diastolic function and atrial conduction time were similar in patients and controls. CONCLUSIONS: Our study suggests that patients with exogenous subclinical hyperthyroidism have hemodynamic changes resulting from adaptation to the biological effects of levothyroxine on the cardiovascular system. However, structural changes are not produced.

Cambios hemodinamicos precoces en pacientes con resistencia insulínica

Objetivos: Determinar cambios hemodinámicos, estructurales y funcionales de pacientes con resistencia insulínica y sin síndrome metabólico. Métodos: Se seleccionaron diez pacientes de ambos sexos con diagnóstico de resistencia insulínica. Diez pacientes sanos ajustados por edad, sexo e índice de masa corporal (IMC) constituyeron el grupo control. El IMC y la presión arterial fueron registrados. Los pacientes fueron sometidos a una prueba de tolerancia oral a la glucosa. El índice de HOMAIR fue utilizado para el cálculo de la resistencia insulínica (HOMAIR: valor ≥ 2,5). La concentración de norepinefrina plasmática (NE) se cuantifico por HPLC. Los parámetros hemodinámicos, estructurales y funcionales del corazón fueron evaluados mediante el ecocardiograma bidimensional, eco doppler pulsado y doppler pulsado tisular. Resultados: La glucemia, la insulina basal y post-carga y el HOMAIR fueron significativamente más altos en el grupo de pacientes. El índice cardiaco resultó significativamente más bajo en el grupo de pacientes. La concentración de NE se correlacionó en forma positiva y estadísticamente significativa con las concentraciones de insulina basal y post-carga. La presión arterial diastólica se correlacionó en forma negativa y estadísticamente significativa con la insulina post-carga solo en el grupo control. El volumen diastólico final del ventrículo izquierdo se correlacionó en forma positiva y estadísticamente significativa con la insulina y el HOMAIR en el grupo de pacientes pero no en el grupo control. Conclusiones: Los niveles de insulina plasmática podrían desempeñar un papel muy importante en la modulación de los niveles plasmáticos de NE en pacientes con resistencia insulínica. La sobreactivación del sistema nervioso simpático podría condicionar anormalidades en el volumen sistólico final y el índice cardiaco, los cuales constituirían los cambios hemodinámicos adaptativos precoces en pacientes con resistencia insulínica sin síndrome metabólico.

Objective: To determine the haemodynamic, structural and functional changes in insulin-resistant subjects Methods: Ten insulin-resistant subjects were studied. Asymptomatic subjects were studied as a control group. Blood pressure and body mass index were registered. Standard oral glucose tolerance test was performed. Plasma glucose and insulin were measured at baseline and 2 hours post glucose load. Insulin resistance index HOMAIR was calculated. Insulin resistance was considered if HOMAIR value was ≥ 2.5. Plasma norepinephrine (NE) was measured by HPLC. In order to examine the mass and cardiac function, bi-dimensional echocardiogram and imaging doppler tissue were performed. Results: Plasma glucose, insulin and HOMAIR were significantly higher in insulin-resistant subjects. There was no significant difference in plasma NE concentration between groups. The cardiac index was the only haemodynamic variable found to be significantly lowers in insulin resistant subjects. A significant positive correlation between NE with fasting and post load insulin concentration was observed. In control group, a significant negative correlation between diastolic blood pressure and post load insulin concentration was observed. The left ventricle systolic end-volume was positively and significantly correlated with insulin and HOMAIR in insulin-resistant subjects, but not in controls. Conclusions: Insulin levels may play role in modulating plasma NE levels, particularly in insulin-resistant subjects. The increased sympathetic activity in these subjects might lead to an abnormality in the left ventricle systolic end-volume and cardiac index, which might be the earlier adaptative haemodynamic changes due to cardiac post-load.

Mechanisms of neurohormonal activation in chronic congestive heart failure: pathophysiology and therapeutic implications.

Patients with chronic congestive heart failure have a sequential and incessant activation of those neurohormonal systems, which control body fluids, cardiac output and systemic blood pressure. Neurohormonal activation is initially selective and regional. Generalized activation is a late event in the natural history of congestive heart failure. Although the ultimate stimulus responsible for the activation of these neurohormonal systems is unknown, a decreased cardiac output and diminished effective blood volume have been proposed as the responsible mechanisms. However, extensive clinical and experimental research suggest that cardiac remodeling and loading of low-pressure cardiac receptors with sympathetic afferents could be the triggering events followed by unloading of high-pressure carotid receptors by decreased cardiac output and diminished effective blood volume.