Biomarkers, medical treatment and fetal intrapartum surveillance in intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterized by maternal pruritus and elevated liver enzymes. It usually begins in the third trimester of pregnancy and resolves spontaneously after delivery. ICP is considered benign for the pregnant woman, but it is associated with an increased risk for unexplained term stillbirth and preterm delivery. There are no specific laboratory markers to diagnose ICP. The diagnosis is currently based on the presence of maternal pruritus and elevated values of alanine aminotransaminases (ALT) and serum bile acids (BA). Recently, ursodeoxycholic acid (UDCA) has been used for treatment. Mechanisms leading to intrauterine fetal death (IUFD) may be multifactorial and are unknown at present. For this thesis, 415 pregnant women with ICP were studied. The aim was to evaluate the value of the liver enzyme glutathione S-transferase alpha (GSTA) as a specific marker of ICP and to assess the effect of maternal UDCA therapy on maternal laboratory values and fetal outcome. The specific markers predisposing the fetus to heart arrhythmia were studied by comparing waveform analysis of fetal electrocardiograms (FECG) during labor in pregnancies complicated by ICP with controls. The levels of maternal GSTA were high and the values correlated with the value of ALT in patients with ICP. UDCA therapy reduced the values of the liver enzymes and alleviated maternal pruritus, but it did not influence maternal hormonal values. Although the newborns experienced an uneventful perinatal outcome, severe ICP was still associated with preterm birth and admission to the neonatal intensive care unit (NICU). There were no significant differences in intrapartum FECG findings between fetuses born to ICP women and controls.

Prolongation de l’intervalle QT corrigé chez les adultes atteints de lupus érythémateux disséminé porteurs de l’anticorps anti-Ro/SSA

La prolongation de l’intervalle électrocardiographique QT est un facteur de risque d’arythmie ventriculaire et de mort subite. Cette anomalie, retrouvée chez certains patients atteints de lupus érythémateux disséminé, pourrait contribuer à la mortalité cardiovasculaire élevée dans cette population. L’anti-Ro/SSA, un auto-anticorps retrouvé chez environ 30% des patients atteints de lupus, est associé à la présence de blocs cardiaques chez le nouveau-né et pourrait aussi augmenter le risque de prolongation pathologique de l’intervalle QT chez l’adulte. Le présent mémoire est constitué de cinq chapitres traitant de l’association potentielle entre l’anticorps anti-Ro/SSA et la prolongation de l’intervalle QT. Le premier chapitre constitue une introduction permettant de mettre en contexte les éléments essentiels à la compréhension du projet d’étude. Le deuxième chapitre constitue une revue de l’état des connaissances actuelles sur le lien potentiel entre anti-Ro/SSA et intervalle QT. Le troisième chapitre présente le projet d’étude par l’intermédiaire d’un article publié dans Arthritis Care and Research. Dans cette étude, les patients de la cohorte de lupiques du Centre Universitaire de santé McGill ont subi des électrocardiogrammes dans l’objectif d’estimer l’association entre l’anti-Ro/SSA et les anomalies électrocardiographiques, en tenant compte d’autres facteurs démographiques et cliniques. L’association entre la prolongation de l’intervalle QT et la présence de l’anti-Ro/SSA a été démontrée (rapports de cotes ajustés de 5.1 à 12.6) et les patients porteurs de l’anti-Ro/SSA pourraient donc bénéficier de dépistage électrocardiographique systématique. Les points faibles et forts de cet article sont discutés dans le quatrième chapitre et des perspectives de recherches futures sont finalement abordées.

Influence de la testostérone sur les paramètres électrocardiographiques des hommes et des femmes

Les hommes et les femmes diffèrent devant la survenue de plusieurs types d’arythmies cardiaques. Ainsi, la prévalence des fibrillations auriculaires, ou celle du syndrome de Brugada est plus élevée chez les hommes, tandis que les femmes sont plus susceptibles de développer des torsades de pointe. La survenue de ces arythmies pourrait être affectée par l’existence de disparités entre les sexes au niveau de l’activité électrique cardiaque normale. Des différences ont d’ailleurs été décrites dans les paramètres électrocardiographiques des hommes et des femmes, et notamment au niveau des paramètres traduisant la phase de repolarisation ventriculaire. Par ailleurs, plusieurs études cliniques et expérimentales ont permis d’avancer que les androgènes pourraient contribuer à expliquer les différences homme-femme observées dans la repolarisation ventriculaire. Leur influence sur les autres paramètres électrocardiographiques a toutefois reçu peu d’attention jusqu’à aujourd’hui. Dans ce contexte, l’objectif de ce travail était de mieux comprendre l’implication de la testostérone dans les différences sexuelles observées au niveau de l’électrocardiogramme. En travaillant à partir d’une cohorte de volontaires sains, nous avons tout d’abord confirmé l’existence de différences électrocardiographiques rapportées précédemment dans la littérature. Nous avons de plus noté un segment PR plus long chez les hommes, bien que l’onde P et l’intervalle PR n’étaient pas significativement différents entre les sexes. Par la suite, nous avons évalué l’association de la testostérone avec les différents paramètres de l’électrocardiogramme humain. La testostérone était le plus fortement associée au complexe QRS, au segment ST et à l’intervalle QTc. Nous avons donc examiné la contribution de la testostérone dans les mécanismes responsables des différences sexuelles pour ces trois paramètres. D’après les résultats obtenus, la testostérone ne semblait toutefois pas expliquer ces différences homme-femme. En conclusion, les résultats de cette étude suggèrent que la testostérone n’est pas responsable des différences observées au niveau du complexe QRS, du segment ST et de l’intervalle QTc des hommes et des femmes de notre cohorte. D’autres médiateurs, seuls ou en association avec la testostérone, pourraient jouer un rôle dans l’établissement de ces différences électrocardiographiques associées au sexe.

Concordancia en interpretación electrocardiográfica en síndromes coronarios agudos entre especialistas del servicio de urgencias y cardiólogos

Introducción: El ECG es una herramienta básica en el estudio del dolor torácico, no hay evidencia que demuestre si la interpretación electrocardiográfica de los especialistas de medicina interna y emergencias es similar a la de cardiólogos en casos de SCA. El propósito de este estudio es determinar si existe concordancia en interpretación de los hallazgos electrocardiográficos más frecuentes en la fase aguda de los síndromes coronarios. Metodología: Estudio retrospectivo de concordancia diagnóstica electrocardiográfica, realizado en un hospital universitario de cuarto nivel. Se escogieron los hallazgos electrocardiográficos más frecuentes en síndromes coronarios agudos para ser evaluados por 3 diferentes especialidades y se hizo el análisis de concordancia mediante el cálculo estadístico kappa. Resultados: Se analizaron 200 electrocardiogramas aleatorizados, de pacientes con SCA entre noviembre de 2012 a abril de 2013. La edad promedio fue 65,14 años, la mayoría hombres (62,5%), la hipertensión arterial y enfermedad coronaria fueron las comorbilidades más frecuentes. Se encontró un grado de concordancia moderada (k = 0.61 – 0.80, p <0.001) entre cardiólogos vs emergenciólogos y cardiólogos vs internistas, excepto en lesión subendocárdica (k = 0.11 y 0.24 respectivamente), hubo un grado de concordancia débil (k = 0.41 – 0.60, p <0.001) entre emergenciólogos e internistas. El hallazgo en el que hubo grado de concordancia muy bueno (k > 0.81) fue bloqueo de rama izquierda. Conclusión: Existe grado de concordancia moderada en la lectura electrocardiográfica en la mayoría de variables en relación con síndrome coronario agudo entre los especialistas de medicina interna y emergencias al compararlo con cardiólogos.

Variabilidade da freqüência cardíaca em cães anestesiados com infusão contínua de propofol e sufentanil

Foram avaliados os efeitos do propofol associado ao sufentanil sobre o balanço das atividades simpática e parassimpática do coração, investigando-se um possível efeito dose dependente do opióide. Analisou-se a variabilidade da freqüência cardíaca (VFC) de 12 cães adultos pré-medicados com maleato de acepromazina e anestesiados com propofol e três doses diferentes de sufentanil, que variou de 0,025 a 0,1µg/kg/min. Registrou-se o eletrocardiograma 15 minutos após a medicação pré-anestésica e 15, 30, 60, 90 e 120 minutos após a indução anestésica. A VFC foi calculada no domínio da freqüência, mediante análise de 10 intervalos RR consecutivos. Houve redução acentuada da freqüência cardíaca, mas a VFC permaneceu relativamente inalterada.

Electrocardiographic evaluation of two anesthetic combinations in dogs

Este trabalho teve o objetivo de avaliar as possíveis alterações eletrocardiográficas de cães submetidos a duas condutas anestésicas, indicando aquela que produz menores alterações no eletrocardiograma (ECG). Foram utilizados 40 cães com idade igual ou superior a cinco anos, 24 machos e 16 fêmeas, com peso entre 5 e 42kg, oriundos de clínicas particulares da cidade de São Paulo e do canil da Polícia Militar do Estado de São Paulo, sem sintomas cardiovasculares e triados para tartarectomia. Todos os cães foram submetidos a dois ECG: um antes da anestesia e outro imediatamente antes de se iniciar o procedimento cirúrgico. As características eletrocardiográficas avaliadas foram: ritmo, duração da onda P, do complexo QRS e dos intervalos PR e QT, amplitude das ondas P e R e alterações do segmento ST e da onda T; avaliou-se também o índice de tono vagal (ITV). Os cães foram divididos em: grupo 1, que recebeu atropina, levomepromazina, tiopental e halotano (ALTH) e grupo 2, que recebeu atropina, tiletamina e zolazepam (ATZ). Os resultados mostraram que a associação ALTH produziu algumas alterações discretas no ECG dos cães avaliados, caracterizadas por modificações qualitativas no segmento ST, na onda T e no ritmo cardíaco, reduzindo significativamente o ITV, com tendência à bradicardia e hipóxia. Já a associação ATZ, além das alterações já citadas, produziu diminuição da duração dos intervalos PR e QT, bem como aumentou a freqüência cardíaca, com tendência à taquicardia e hipóxia.

Eletrocardiografia computadorizada em cães

O objetivo deste trabalho foi analisar e comparar os registros eletrocardiográficos de cães clinicamente normais, obtidos pelos métodos convencional, computadorizado e pela leitura direta do registro computadorizado impresso, visando padronizar o método informatizado e confrontá-lo com o convencional. Concluiu-se que existem diferenças quanto a amplitude e duração da onda P e duração do complexo QRS entre diferentes métodos, especialmente em relação ao computadorizado, devendo-se sempre levar em consideração esse fato durante a interpretação dos exames.

Análise e síntese de um processador digital wavelet

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cardiovascular risk in Japanese-Brazilian subjects

Objective: To evaluate the prevalence of risk factors for cardiovascular disease in Japanese-Brazilian subjects. Subjects and methods: One hundred thirty-one residents of the Mombuca community were studied. Statistical analysis was based on the X-2 test, Fisher's Exact test, Student's t test, and ANOVA, at a 5% significance level. Results: The average age was 56.7 years-old; 76.3% had dyslipidemia, 24.4% pre-diabetes (PDM), 10.7% type 2 diabetes mellitus (T2DM), 46.6% hypertension, 52.7% abdominal obesity, and 35.8% metabolic syndrome (MS). There were significant correlations between HOMA-IR and MS diagnosis and obesity, while HOMA-beta levels were decreased in T2DM and PDM. The ankle-brachial index was positive for peripheral artery disease in 22.3% of the individuals. Electrocardiograms did not show increased evidence of myocardial ischemia. Conclusion: Subjects of this community are exposed to major cardiovascular risk factors, namely high prevalence of MS diagnoses and increased HOMA-IR. Arq Bras Endocrinol Metab. 2012; 56(9): 608-13

A study of effectiveness of midazolam sedation for prevention of myocardial arrhythmias in endosseous implant placement

Purpose: The study aimed to assess electrocardiographic alterations during oral implant placement surgeries under local anesthesia (lidocaine chlorhydrate with epinephrine), using 15 mg of midazolam as an anxiolytic premedication. Material and methods: The study randomly selected 20 patients, aged 21-50 years old, requiring bilateral mandibular dental implants. Each patient was assessed using placebo on one side and midazolam on the contralateral side, with random, double-blinded distribution. The electrocardiogram recorded 12 static leads every 2 min, while D2 derivations were recorded continuously. Results: No statistically significant differences were observed between the placebo and midazolam when analyzing the morphological behavior of the electrocardiographic wave and the presence of arrhythmias during the experiment. However, under sedation, assessment of the behavior of electrocardiographic parameters during different stages of the procedure revealed statistically significant differences (P<0.05) for heart rate, P-wave amplitude and duration of the RR and QTc intervals. The arrhythmias detected were considered low risk for patients without systemic alterations and were observed in 53.3% of patients. The most frequently occurring alterations were tachycardia, bradycardia, supraventricular and ventricular extrasystoles and blocked atrial extrasystole, which were similar for both placebo and midazolam, with the greatest incidence during the initial, incision and bone drilling stages. Conclusion: The use of 15 mg of midazolam made no difference compared with the placebo. The use of 15 mg of midazolam did not show an advantage in the incidence of arrhythmias The anxiolytic premedication does not prevent myocardial arrhythmias in endosseous implant placement. The clinical significance of the arrhythmias may not represent serious risks.

Performance of rest myocardial perfusion imaging in the management of acute chest pain in the emergency room in developing nations (PREMIER trial)

Background. Rest myocardial perfusion imaging (MPI) is effective in managing patients with acute chest pain in developed countries. We aimed to define the role and feasibility of rest MPI in low-to-middle income countries. Methods and Results. Low-to-intermediate risk patients (n = 356) presenting with chest pain to ten centers in eight developing countries were injected with a Tc-99m-based tracer, and standard imaging was performed. The primary outcome was a composite of death, non-fatal myocardial infarction (MI), recurrent angina, and coronary revascularization at 30 days. Sixty-nine patients had a positive MPI (19.4%), and 52 patients (14.6%) had a primary outcome event. An abnormal rest-MPI result was the only variable which independently predicted the primary outcome [adjusted odds ratio (OR) 8.19, 95% confidence interval 4.10-16.40, P = .0001]. The association of MPI result and the primary outcome was stronger (adjusted OR 17.35) when only the patients injected during pain were considered. Rest-MPI had a negative predictive value of 92.7% for the primary outcome, improving to 99.3% for the hard event composite of death or MI. Conclusions. Our study demonstrates that rest-MPI is a reliable test for ruling out MI when applied to patients in developing countries. (J Nucl Cardiol 2012;19:1146-53.)

Cardiovascular risk in Japanese-Brazilian subjects

OBJECTIVE: To evaluate the prevalence of risk factors for cardiovascular disease in Japanese-Brazilian subjects. SUBJECTS AND METHODS: One hundred thirty-one residents of the Mombuca community were studied. Statistical analysis was based on the X² test, Fisher's Exact test, Student's t test, and ANOVA, at a 5% significance level. RESULTS: The average age was 56.7 years-old; 76.3% had dyslipidemia, 24.4% pre-diabetes (PDM), 10.7% type 2 diabetes mellitus (T2DM), 46.6% hypertension, 52.7% abdominal obesity, and 35.8% metabolic syndrome (MS). There were significant correlations between HOMA-IR and MS diagnosis and obesity, while HOMA-β levels were decreased in T2DM and PDM. The ankle-brachial index was positive for peripheral artery disease in 22.3% of the individuals. Electrocardiograms did not show increased evidence of myocardial ischemia. CONCLUSION: Subjects of this community are exposed to major cardiovascular risk factors, namely high prevalence of MS diagnoses and increased HOMA-IR. Arq Bras Endocrinol Metab. 2012;56(9):608-13

Trigger activity more than three years after left atrial linear ablation without pulmonary vein isolation in patients with atrial fibrillation.

OBJECTIVES The aim of this study was to analyze trigger activity in the long-term follow-up after left atrial (LA) linear ablation. BACKGROUND Interventional strategies for curative treatment of atrial fibrillation (AF) are targeted at the triggers and/or the maintaining substrate. After substrate modification using nonisolating linear lesions, the activity of triggers is unknown. METHODS With the LA linear lesion concept, 129 patients were treated using intraoperative ablation with minimal invasive surgical techniques. Contiguous radiofrequency energy-induced lesion lines involving the mitral annulus and the orifices of the pulmonary veins without isolation were placed under direct vision. RESULTS After a mean follow-up of 3.6 +/- 0.4 years, atrial ectopy, atrial runs, and reoccurrence of AF episodes were analyzed by digital 7-day electrocardiograms in 30 patients. Atrial ectopy was present in all patients. Atrial runs were present in 25 of 30 patients (83%), with a median number of 9 runs per patient/week (range 1 to 321) and a median duration of 1.2 s/run (range 0.7 to 25), without a significant difference in atrial ectopy and atrial runs between patients with former paroxysmal (n = 17) or persistent AF (n = 13). Overall, 87% of all patients were completely free from AF without antiarrhythmic drugs. CONCLUSIONS A detailed rhythm analysis late after specific LA linear lesion ablation shows that trigger activity remains relatively frequent but short and does not induce AF episodes in most patients. The long-term success rate of this concept is high in patients with paroxysmal or persistent AF.

Differentiating atrioventricular nodal reentrant tachycardia from tachycardia via concealed accessory pathway.

Studies analyzing the diagnostic value of 12-lead electrocardiographic criteria differentiating slow-fast atrioventricular nodal reentrant tachycardia (AVNRT) from atrioventricular reentrant tachycardia (AVRT) due to concealed accessory pathway have shown inconsistent results. In 97 patients (50 with AVNRT, 47 with AVRT) 12-lead electrocardiograms (ECGs) were recorded during sinus rhythm and tachycardia (QRS <120 ms). The ECGs were blinded for diagnosis and patient and analyzed independently by 2 electrophysiologists. The studied criteria differentiating AVNRT from AVRT included pseudo-r'/S, the presence of a retrograde P wave, RP interval, ST-segment depression >/=2 mm with the number and location of the affected leads, QRS amplitude, and cycle length alternans.

Outflow tract tachycardia with R/S transition in lead V3: six different anatomic approaches for successful ablation.

OBJECTIVES The aim of this study was to analyze different anatomic mapping approaches for successful ablation of outflow tract tachycardia with R/S transition in lead V(3). BACKGROUND Idiopathic ventricular tachycardia can originate from different areas in the outflow tract, including the right and left ventricular endocardium, the epicardium, the pulmonary artery, and the aortic sinus of Valsalva. Although electrocardiographic criteria may be helpful in predicting the area of origin, sometimes the focus is complex to determine, especially when QRS transition in precordial leads is in V(3). METHODS We analyzed surface electrocardiograms of 33 successfully ablated patients with outflow tract tachycardia: 20 from the right ventricular outflow tract (RVOT) and 13 from different sites. The R/S transition was determined, and the different anatomic approaches needed for successful catheter ablation were studied. RESULTS Overall, R/S transition in lead V(3) was present in 19 (58%) of all patients. In these patients, mapping was started and successfully completed in the RVOT in 11 of 19 (58%) patients. The remaining eight patients with R/S transition in lead V(3) needed five additional anatomic accesses for successful ablation: from the left ventricular outflow tract (n = 3), aortic sinus of Valsalva (n = 2), coronary sinus (n = 1), the epicardium via pericardial puncture (n = 1), and the trunk of the pulmonary artery (n = 1), respectively. CONCLUSIONS A R/S transition in lead V(3) is common. In patients with outflow tract tachycardia with R/S transition in lead V(3), a stepwise endocardial and epicardial mapping through up to six anatomic approaches can lead to successful radiofrequency catheter ablation.