Early exposure to mercury and cardiovascular function of seven-year old children in Guadeloupe (French West Indies).

BACKGROUND: The cardiotoxicity of prenatal exposure to mercury has been suggested in populations having regular contaminated seafood intake, though replications in the literature are inconsistent. METHODS: The Timoun Mother-Child Cohort Study was set up in Guadeloupe, an island in the Caribbean Sea where seafood consumption is regular. At seven years of age, 592 children underwent a medical examination, including cardiac function assessment. Blood pressure (BP) was taken using an automated blood pressure monitor, heart rate variability (HRV, 9 parameters) and electrocardiogram (ECG) characteristics (QT, T-wave parameters) were measured using Holter cardiac monitoring during the examination. Total mercury concentrations were measured in cord blood at birth (median = 6.6 µg/L, N = 399) and in the children's blood at age 7 (median = 1.7 µg/L, N = 310). Adjusted linear and non-linear modelling was used to study the association of each cardiac parameter with prenatal and childhood exposures. Sensitivity analyses included co-exposures to lead and cadmium, adjustment for maternal seafood consumption, selenium and polyunsaturated fatty acids (n3-PUFAs), and for sporting activity. RESULTS: Higher prenatal mercury was associated with higher systolic BP at 7 years of age (ßlog2 = 1.02; 95% Confidence Interval (CI) = 0.10, 1.19). In boys, intermediate prenatal exposure was associated with reduced overall HRV and parasympathetic activity, and longer QT was observed with increasing prenatal mercury (ßlog2 = 4.02; CI = 0.48, 7.56). In girls, HRV tended to increase linearly with prenatal exposure, and no association was observed with QT-wave related parameters. Mercury exposure at 7 years was associated with decreased BP in girls (ßlog2 = -1.13; CI = -2.22, -0.004 for diastolic BP). In boys, the low/high-frequency (LF/HF) ratio increased for intermediate levels of exposure. CONCLUSION: Our study suggests sex-specific and non-monotonic modifications in some cardiac health parameters following prenatal exposure to mercury in pre-pubertal children from an insular fish-consuming population.

Polyester Nanocapsules for Intravenous Delivery of Artemether: Formulation Development, Antimalarial Efficacy, and Cardioprotective Effects In Vivo.

Artemether (ATM) is an effective antimalarial drug that also has a short half-life in the blood. Furthermore, ATM is also cardiotoxic and is associated with pro-arrhythmogenic risks. We aimed to develop a delivery system enabling the prolonged release of ATM into the blood coupled with reduced cardiotoxicity. To achieve this, we prepared polymeric nanocapsules (NCs) from different biodegradable polyesters, namely poly(D,L-lactide) (PLA), poly-ε-caprolactone (PCL), and surface-modified NCs, using a monomethoxi-polyethylene glycol-block-poly(D,L-lactide) (PEG5kDa-PLA45kDa) polymer. Using this approach, we were able to encapsulate high yields of ATM (>85%, 0−4 mg/mL) within the oily core of the NCs. The PCL-NCs exhibited the highest percentage of ATM loading as well as a slow release rate. Atomic force microscopy showed nanometric and spherical particles with a narrow size dispersion. We used the PCL NCs loaded with ATM for biological evaluation following IV administration. As with free-ATM, the ATM-PCL-NCs formulation exhibited potent antimalarial efficacy using either the "Four-day test" protocol (ATM total at the end of the 4 daily doses: 40 and 80 mg/kg) in Swiss mice infected with P. berghei or a single low dose (20 mg/kg) of ATM in mice with higher parasitemia (15%). In healthy rats, IV administration of single doses of free-ATM (40 or 80 mg/kg) prolonged cardiac QT and QTc intervals and induced both bradycardia and hypotension. Repeated IV administration of free-ATM (four IV doses at 20 mg/kg every 12 h for 48 h) also prolonged the QT and QTc intervals but, paradoxically, induced tachycardia and hypertension. Remarkably, the incorporation of ATM in ATM-PCL-NCs reduced all adverse effects. In conclusion, the encapsulation of ATM in biodegradable polyester NCs reduces its cardiovascular toxicity without affecting its antimalarial efficacy.

Severe primary hypothyroidism presenting as polymorphic ventricular tachycardia / Hipotiroidismo primario grave que se presenta como taquicardia ventricular polimórfica

Abstract Introduction: Hypothyroidism may have various cardiovascular manifestations due to morphological, functional and electrical alterations in the heart. The usual electrocardiographic findings being sinus bradycardia, low voltage complexes, and slowed intraventricular conduction. Hypothyroidism manifesting as polymorphic ventricular tachycardia has only been reported in a few case reports. Clinical case. A 60-year-old lady presented to us in the emergency department in an unresponsive and unconscious state and electrocardiogram showed a polymorphic ventricular tachycardia. After initial resuscitation with direct current cardioversion and supportive care, she found to have severe hypothyroidism and responded well to thyroid replacement therapy. Conclusion. Polymorphic ventricular tachycardia is a life threatening emergency that can have various etiologies. Polymorphic ventricular tachycardia secondary to primary hypothyroidism is a rare presentation but it is treatable and reversible with thyroid replacement therapy. In patients presenting with QT interval prolongation and ventricular tachycardia, hypothyroidism should be one of the differential diagnosis.

Resumen Introducción: El hipotiroidismo puede presentar diferentes manifestaciones cardiovasculares dadas por alteraciones morfológicas, funcionales y eléctricas en el corazón, siendo los hallazgos electrocardiográficos usuales son la bradicardia sinusal, los complejos de bajo voltaje y la conducción intraventricular lenta. El hipotiroidismo manifestado como taquicardia ventricular polimórfica solo se ha descrito en unos pocos reportes de caso. Caso clínico: Se trata de una mujer de 60 años que acudió que acurdió al servicio de urgencias en un estado inconsciente y sin respuesta a estímulos, y el electrocardiograma reveló taquicardia ventricular polimórfica. Luego de la reanimación inicial con cardioversión con corriente directa y tratamiento sintomático se le encontró un hipotiroidismo grave, el cual se trató con terapia de reemplazo con hormona tiroidea. y se obtuvo una buena respuesta Conclusión. La taquicardia ventricular polimórfica es una emergencia vital que puede tener varias etiologías. La taquicardia ventricular polimórfica secundaria a un hipotiroidismo primario es una presentación poco común, pero es tratable y reversible con la terapia de reemplazo con hormona tiroidea. En los pacientes que presentan una prolongación del intervalo QT y taquicardia ventricular, es pertinente incluir el hipotiroidismo en el diagnóstico diferencial.

Arritmias ventriculares en el síndrome de takotsubo: cuestión de sexo / Sex-related risk of arrhythmia in takotsubo syndrome

Resumen El síndrome de takotsubo, también conocido como miocardiopatía de estrés, representa un difícil reto diagnóstico, pues en muchos casos su presentación es superponible al infarto de miocardio por ruptura de placa; el diagnóstico definitivo se basa en la ausencia de lesiones culpables en la coronariografía. La fisiopatología de la enfermedad no está por completo establecida, y tiene un pronóstico generalmente benigno. Sin embargo, existe un porcentaje no despreciable de pacientes que sufren complicaciones graves, entre las que destacan las arritmias malignas tipo taquicardia ventricular polimórfica por prolongación del intervalo QT. A pesar de que el síndrome de takotsubo afecta principalmente a las mujeres, quienes por otra parte también suelen tener intervalos QT más prolongados en condiciones basales, la muerte súbita de origen arrítmico aparece con mayor frecuencia en los hombres que sufren esta enfermedad. Se presentan dos casos de ensanchamiento extremo del intervalo QT corregido en pacientes con takotsubo que tuvieron desenlaces diferentes. El propósito de este trabajo es destacar y revisar las diferencias electrocardiográficas y pronósticas relacionadas con el sexo de los sujetos que desarrollan esta controvertida enfermedad.

Abstract Takotsubo syndrome, also known as stress cardiomyopathy, is a difficult diagnostic challenge as, in many cases, its presentation can overlap with that of myocardial infarction due to plaque rupture. The definitive diagnosis is based on the lack of culprit lesions on coronariography. The pathophysiology of the disease has not been completely ascertained, and it has a generally benign prognosis. However, a not inconsiderable percentage of patients experience serious complications, notably malignant arrhythmias like polymorphic ventricular tachycardia due to a prolonged QT interval. Despite takotsubo syndrome affecting mainly women who, furthermore, generally have longer basal QT intervals, sudden death due to arrhythmias is more common in men with this disease. Two cases are presented of extremely prolonged corrected QT intervals in patients with takotsubo, with different outcomes. The purpose of this paper is to highlight and review the electrocardiographic and prognostic differences related to the gender of the individuals who develop this controversial disease.

Caspofungin Effects on Electrocardiogram of Mice: An Evaluation of Cardiac Safety.

Caspofungin is an echinocandin, exhibiting efficacy against most Candida species invasive infection. Its cardiotoxicity was reported in isolated rat heart and ventricular myocytes, but in vivo and clinical studies are insufficient. Our objective was to evaluate caspofungin in vivo cardiac effects using an efficacious dose against Candida albicans. Female Swiss mice were infected with C. albicans, and treated with caspofungin, 5 or 10 mg/kg, intraperitoneal along 5 days. Survival rate and colony-forming units (CFU) into vital organs were determined. For cardiac effects study, mice were treated with caspofungin 10 mg/kg, and electrocardiogram (ECG) signal was obtained on C. albicans-infected mice, single dose-treated, and uninfected mice treated along 5 days, both groups to measure ECG intervals. Besides, ECG was also obtained by telemetry on uninfected mice to evaluate heart rate variability (HRV) parameters. The MIC for caspofungin on the wild-type C. albicans SC5314 strain was 0.3 µg/ml, indicating the susceptible. Survival rate increased significantly in infected mice treated with caspofungin compared to mice treated with vehicle. None of the survived infected mice presented positive CFU after treatment with 10 mg/kg. C. albicans infection induced prolongation of QRS, QT, and QTc intervals; caspofungin did not alter this effect. Caspofungin induced increase of PR and an additional increase of QRS after 24 h of a single dose in infected mice. No significant alterations occurred in ECG intervals and HRV parameters of uninfected mice, after caspofungin treatment. Caspofungin showed in vivo cardiac relative safety maintaining its antifungal efficacy against C. albicans.

Analysis of the Incidence and Clinical Significance of Long and Short Corrected QT Interval in Electrocardiogram in Healthy Population of Changsha in China

ABSTRACT Objective: To analyse the incidence of long and short corrected QT (QTc) in a healthy sample of the population of Changsha in China. Methods: Standard 12-lead electrocardiograms (ECGs) were performed on 4025 subjects in Changsha of China, whose age ranged from 6 minutes after birth to 83 years, between January 1993 and December 2012. Heart rate and QT interval were measured and recorded. Corrected QT was calculated with Bazett´s formula (QTc = QT/RR0.5). All recruited individuals had taken healthy examination, ruling out general health issue, in The Second Xiangya Hospital of Central South University. Statistical analyses were performed using the SPSS 16.0 software (IBM Corp, Armonk, NY, USA). Results: The incidence of short QTc was 7.13% (287/4025 cases). The peak values of the incidence were in the 30-40 years group (15.71%). The low values were in the 1-3 months group and 3-6 months group (0%, 0.76%), respectively. The incidence of long QTc was 3.16% (127/4025 cases). The values diminished significantly after adulthood. The low values were in the age groups of 18-30 years (0.86%) and 30-40 years (0.71%), respectively. After the age of 50 years, the incidence of long QTc increased with age 50-60 years and 60-70 years and 70-83 years (7.89%, 9.06%, 14.06%), respectively. There was no statistically significant difference between the genders (p > 0.05). Conclusion: The peak incidences of long and short QTc existed in two separate age groups in the healthy sample. The peak incidence of short QTc was in the age group of 18-40 years, and the peak incidence of long QTc was in the age group beyond the 50 years. For these two age groups, it was recommended to pay close attention to the changes in their QTc in order to prevent cardiovascular events.

Variables electrocardiográficas asociadas a la aparición de eventos cardiovasculares adversos en el infarto agudo de miocardio sin elevación del segmento ST / Electrocardiographic variables associated to the occurrence of adverse cardiovascular events in non-ST elevation acute myocardial infarction

Introducción: La frecuencia de infarto agudo de miocardio sin elevación del segmento ST se está incrementando y, con ella, los resultados adversos en pacientes con enfermedad coronaria isquémica aguda. Objetivo: Identificar las variables electrocardiográficas asociadas a la aparición de eventos cardiovasculares adversos en el infarto agudo de miocardio sin elevación del segmento ST. Método: Se realizó un estudio transversal, de tipo correlacional, con 68 pacientes con infarto agudo de miocardio sin elevación del segmento ST atendidos en el Hospital Arnaldo Milián Castro, en la provincia de Villa Clara. Se estudiaron los hallazgos electrocardiográficos y eventos cardiacos adversos durante el ingreso. Se hicieron análisis bivariados para establecer la relación de ambas variables, utilizando el estadígrafo chi cuadrado y el riesgo relativo. Resultados: Los hallazgos electrocardiográficos más frecuentes fueron la inversión de la onda T (#8805; 2mm), depresión del segmento ST y el QT corregido largo mediante la fórmula de Bazzet. El 26,5 por ciento presentaron eventos cardiovasculares adversos. La depresión del segmento ST, el QT largo corregido y la elevación del segmento ST en aVR se asociaron significativamente con eventos adversos intrahospitalarios (p lt; 0,05). Conclusiones: La asociación de la depresión del segmento ST, la elevación del segmento ST en aVR y el QT largo corregido con la ocurrencia de eventos cardiovasculares adversos intrahospitalarios, sugiere que estos hallazgos se pueden tener en cuenta como posibles indicadores de evolución desfavorable en pacientes con infarto agudo de miocardio sin elevación del segmento ST(AU)

Introduction: The frequency of non-ST elevation acute myocardial infarction is on the increase, and so is the number of adverse results in patients with acute ischemic coronary disease. Objective: Identify the electrocardiographic variables associated to the occurrence of adverse cardiovascular events in non-ST elevation acute myocardial infarction. Method: A cross-sectional correlational study was conducted of 68 patients with non-ST elevation acute myocardial infarction cared for at Arnaldo Milián Castro Hospital in the province of Villa Clara. Attention was paid to electrocardiographic findings and adverse cardiac events occurring during the hospital stay. Bivariate analyses were performed to establish the relationship between the two variables, using the chi square statigram and relative risk estimation. Results: The most common electrocardiographic findings were T-wave inversion (#8805; 2 mm), ST depression and long corrected QT by Bazzet's formula. Of the total study subjects 26.5 percent had adverse cardiovascular events. ST depression, long corrected QT and ST elevation in aVR were significantly associated to in-hospital adverse events (p < 0.05). Conclusions: Association of ST depression, ST elevation in aVR and long corrected QT with the occurrence of adverse in-hospital cardiovascular events suggests that these findings may be taken into account as possible indicators of an unfavorable evolution in patients with non-ST elevation acute myocardial infarction(AU)

Recommendations for the measurement of the QT interval during the use of drugs for COVID-19 infection treatment. Updatable in accordance with the availability of new evidence.

COVID-19 infection has shown rapid growth worldwide, and different therapies have been proposed for treatment, in particular, the combination of immune response modulating drugs such as chloroquine and hydroxychloroquine (antimalarials) alone or in combination with azithromycin. Although the clinical evidence supporting their use is scarce, the off label use of these drugs has spread very quickly in face of the progression of the epidemic and the high mortality rate in susceptible populations. However, these medications can pathologically prolong the QT interval and lead to malignant ventricular arrhythmias such that organized guidance on QT evaluation and management strategies are important to reduce morbidity associated with the potential large-scale use.

Repolarización ventricular en la terapia oncológica / Ventricular repolarization in cancer therapy

RESUMEN Se discuten los procesos de despolarización y repolarización ventriculares, con su falta de uniformidad y su heterogeneidad, tanto en pacientes con corazón sano como en aquellos enfermos, cuestión de rangos. Se analizan las mediciones que expresan las características de la repolarización ventricular: el intervalo QT y otras mediciones incluso más fidedignas como el intervalo TPICO-TFINAL, su dispersión y otras. Se precisa la existencia del signo y del síndrome de QT largo, así como los tres procesos básicos de la arritmogenia: la heterogeneidad, la alternancia y la dispersión, con las diferencias de los potenciales de acción en las tres zonas del miocardio ventricular. Se precisan los factores de riesgo del QT largo (común con esta terapia), de las arritmias ventriculares (en especial la torsión de puntas, extremadamente rara en estos casos) y se discute la necesidad de valorar datos clínicos, eléctricos, comorbilidades, conflictos agregados y las medidas a tomar en estos pacientes.

ABSTRACT Ventricular depolarization and repolarization processes are discussed, including their differences and heterogeneity both in patients with a healthy/sick heart, a matter of ranges. Measurements expressing the characteristics of ventricular repolarization are analyzed: the QT interval and other even more reliable measurements such as the TPEAK-TEND interval, its dispersion and others. We emphasize on the existence of the long QT syndrome (and sign) and the three basic processes of arrhythmogenesis: heterogeneity, alternation and dispersion, with differences in action potentials in the three zones of the ventricular myocardium. The risk factors of long QT (common in this therapy) and ventricular arrhythmias (especially torsades de pointes, extremely rare in these cases) are highlighted. The need to assess clinical and electrical features, comorbidities, aggregate conflicts, and management of these patients is also discussed.

Comparación de cuatro fórmulas para ajustar el intervalo QT a la frecuencia cardiaca en pacientes cardiópatas / Comparison of four formulas to adjust the QT interval to the heart rate in a cardiac patient / Comparação de quatro fórmulas para ajustar o intervalo QT à freqüência cardíaca em pacientes com doença cardíaca

Resumen. Introducción: La prolongación del intervalo QT en el electrocardiograma es un conocido factor de riesgo para desarrollar eventos cardiovasculares. En Latinoamérica existe poca evidencia acerca de la epidemiología de este tipo de alteraciones electrocardiográficas. El objetivo de este estudio fue evaluar la prevalencia del intervalo QT corregido largo según cuatro fórmulas. Metodología: Estudio descriptivo retrospectivo. Se realizó una revisión de 156 registros electrocardiográficos de 12 derivaciones realizados a pacientes mayores a 40 años. Las medidas se realizaron manualmente y posteriormente los valores se ajustaron a la frecuencia cardiaca mediante cuatro fórmulas validadas existentes. Se consideró intervalo QT largo cuando la duración sobrepasaba los 470 ms. Resultados: De los 156 registros analizados, 55.7% de los registros pertenecieron a pacientes de sexo femenino y la edad media fue 70.3 ± 9.7 años. 9.6% de los registros fueron considerados como largos mediante la fórmula de Bazzet, 4.4% mediante la fórmula de Hodges, 3.8% mediante la fórmula de Fridericia y 3.2% mediante la fórmula deFramingham. La fórmula de Fridericia fue hallada como la más consistente para ajustar el intervalo QT a la frecuencia cardiaca. Conclusión: Dependiendo de la fórmula utilizada la prevalencia del intervalo QT largo varió significativamente. La fórmula de Fridericia fue la que demostró mejor consistencia.

Abstract. Introduction: The prolongation of the QT interval in the electrocardiogram is a well-known risk factor for developing cardiovascular events. In Latin America there is no much evidence about the epidemiology of electrocardiographic alterations. The objective of this study was to evaluate the prevalence of long corrected QT interval according to four formulas. Methodology: Retrospective descriptive study. A total of 156 electrocardiographic records of 12 referrals made to patients older than 40 years were review. The measurements were made manually and later the values ​​were adjusted to the heart rate by means of four existing validated formulas. The long QT interval was considered when the duration exceeded 470ms. Results: Of the 156 records analyzed, 55.7% of the records belonged to female patients and the mean age was 70.3 ± 9.7 years. 9.6% of the records were considered long using the Bazzet formula, 4.4% according to the Hodges formula, 3.8% according to the Fridericia formula and 3.2% according to the Framingham formula. The formula of Fridericia was found to be the most consistent to adjust the QT interval to the heart rate. Conclusion: Depending on the formula used, the prevalence of the long QT interval varied significantly. The formula of Fridericia was the one that showed the best consistency.

Resumo. Introdução: O prolongamento do intervalo QT no eletrocardiograma é um fator de risco conhecido para o desenvolvimento de eventos cardiovasculares. Na América Latina, há poucas evidências sobre a epidemiologia desse tipo de alteração eletrocardiográfica. O objetivo deste estudo foi avaliar a prevalência do intervalo QT longo corrigido de acordo com quatro fórmulas. Metodologia: Estudo descritivo retrospectivo. Uma revisão de 156 registros eletrocardiográficos de 12 derivações realizadas em pacientes com mais de 40 anos foi realizada. As medidas foram feitas manualmente e posteriormente os valores foram ajustados à freqüência cardíaca por meio de quatro fórmulas validadas existentes. O intervalo QT longo foi considerado quando a duração ultrapassou 470 ms. Resultados: Dos 156 prontuários analisados, 55,7% dos prontuários pertenciam a pacientes do sexo feminino e a média de idade foi de 70,3 ± 9,7 anos. 9,6% dos registros foram considerados longos usando a fórmula de Bazzet, 4,4% usando a fórmula de Hodges, 3,8% usando a fórmula de Fridericia e 3,2% usando a fórmula de Fraingham. A fórmula de Fridericia foi considerada a mais consistente para ajustar o intervalo QT à frequência cardíaca. Conclusão: Dependendo da fórmula utilizada, a prevalência do intervalo QT longo variou significativamente. A fórmula da Fridericia foi a que apresentou a melhor consistência.

Assessment and clinical relevance of the dynamic parameters of ventricular repolarization in patients with grade I left ventricular diastolic dysfunction 1.

Imbalance in ventricular repolarization parameters are related to increased risk of severe arrhythmia and sudden cardiac death. There is limited research regarding markers to detect patients at risk in this early stage. We aimed to assess the influence of grade I left ventricular diastolic dysfunction on repolarization parameters in asymptomatic patients. Ambulatory patients with grade I left ventricular diastolic dysfunction were studied and compared with a control group. We assessed the QT dispersion circadian variation, heart rate variability in the time and frequency domains, and dynamics of QT using a 12-lead Holter. In the diastolic dysfunction group, 8 (30%) patients had QT dispersion > 80 ms. One (3.8%) patient presented premature ventricular complex > 10/h. The comparison between the 2 groups showed that the difference between the standard deviation of normal-to-normal intervals and low frequency power in both groups was statistically significant. We therefore conclude that increased parameters of ventricular repolarization and depressed heart rate variability reflect an imbalance in autonomic responses in patients with grade I left ventricular diastolic dysfunction without cardiovascular symptoms, enabling the identification of patients that are at a higher risk for cardiovascular events.

Dispersión del intervalo QT corregido como predictor de arritmias ventriculares en el infarto agudo del miocardio / Dispersion of the corrected QT interval as a predictor of ventricular arrhythmias in acute myocardial infarction

RESUMEN Fundamento: La dispersión del intervalo QT es un marcador electrocardiográfico que puede resultar útil en la estratificación de riesgo arrítmicos en pacientes con infarto agudo del miocardio. Objetivo: Describir la influencia de la dispersión del intervalo QT corregido en asociación a otros factores de riesgo como predictores de arritmias ventriculares en el infarto agudo del miocardio con elevación del segmento ST. Metodología: Se estudiaron de menera prospectiva 209 pacientes que ingresaron de forma consecutiva con diagnóstico de infarto agudo de miocardio con elevación del segmento ST de enero de 2013 a junio de 2014 en el Hospital Provincial General Camilo Cienfuegos de Sancti Spíritus. Se recogieron datos clínicos, de laboratorio electrocardiográficos y ecocardiográficos; se determinó la implicación pronóstica de la dispersión del intervalo QT corregido en la aparición de arritmias ventriculares a través de la regresión logística binaria y las curvas de operador-receptor. Resultados: Las arritmias ventriculares se presentaron en 39 (18.7 %) pacientes. La dispersión del QT corregido mostró una adecuada capacidad de discriminación en la predicción de cualquier episodio arrítmico ventricular grave (c=0.768, p=0.0001). En el análisis multivariado la dispersión del QT resultó un predictor independiente de arritmias ventriculares (OR= 7.075; IC 95%= 1.6- 32.9; p=0.009). Conclusiones: La probabilidad de presentar arritmias ventriculares durante el infarto agudo del miocardio es mayor cuando se incrementan la dispersión del intervalo QT, por lo que se sugiere debe ser una variable a evaluar en la estratificación pronostica del infarto agudo del miocardio.(AU)

ABSTRACT Background: Dispersion of the QT interval is an electrocardiographic marker that can be useful in the stratification of arrhythmic risk in patients with acute myocardial infarction. Objective: To describe the influence of corrected QT interval dispersion in association with other risk factors as predictors of ventricular arrhythmias in acute myocardial infarction with ST-segment elevation. Methodology: 209 patients who entered consecutively with diagnosis of acute myocardial infarction with elevation of the ST segment from January 2013 to June 2014 at Camilo Cienfuegos General Provincial Hospital of Sancti Spíritus were studied prospectively. Clinical, electrocardiographic and echocardiographic laboratory data were collected; the prognostic implication of the corrected QT interval dispersion in the appearance of ventricular arrhythmias through binary logistic regression and operator-receiver curves was determined. Results: Ventricular arrhythmias occurred in 39 (18.7%) patients. The dispersion of the corrected QT showed an adequate discrimination capacity in the prediction of any serious ventricular arrhythmic episode (c = 0.768, p = 0.0001). In the multivariate analysis, QT dispersion was an independent predictor of ventricular arrhythmias (OR = 7.075, 95% CI = 1.6-32.9, p = 0.009). Conclusions: The probability of presenting ventricular arrhythmias during acute myocardial infarction is greater when the dispersion of the QT interval is increased, so it is suggested that it should be a variable to be evaluated in the prognostic stratification of acute myocardial infarction.(AU)

Dispersión del intervalo QT corregido como predictor de arritmias ventriculares en el infarto agudo del miocardio / Dispersion of the corrected QT interval as a predictor of ventricular arrhythmias in acute myocardial infarction

RESUMEN Fundamento: La dispersión del intervalo QT es un marcador electrocardiográfico que puede resultar útil en la estratificación de riesgo arrítmicos en pacientes con infarto agudo del miocardio. Objetivo: Describir la influencia de la dispersión del intervalo QT corregido en asociación a otros factores de riesgo como predictores de arritmias ventriculares en el infarto agudo del miocardio con elevación del segmento ST. Metodología: Se estudiaron de menera prospectiva 209 pacientes que ingresaron de forma consecutiva con diagnóstico de infarto agudo de miocardio con elevación del segmento ST de enero de 2013 a junio de 2014 en el Hospital Provincial General Camilo Cienfuegos de Sancti Spíritus. Se recogieron datos clínicos, de laboratorio electrocardiográficos y ecocardiográficos; se determinó la implicación pronóstica de la dispersión del intervalo QT corregido en la aparición de arritmias ventriculares a través de la regresión logística binaria y las curvas de operador-receptor. Resultados: Las arritmias ventriculares se presentaron en 39 (18.7 %) pacientes. La dispersión del QT corregido mostró una adecuada capacidad de discriminación en la predicción de cualquier episodio arrítmico ventricular grave (c=0.768, p=0.0001). En el análisis multivariado la dispersión del QT resultó un predictor independiente de arritmias ventriculares (OR= 7.075; IC 95%= 1.6- 32.9; p=0.009). Conclusiones: La probabilidad de presentar arritmias ventriculares durante el infarto agudo del miocardio es mayor cuando se incrementan la dispersión del intervalo QT, por lo que se sugiere debe ser una variable a evaluar en la estratificación pronostica del infarto agudo del miocardio.

ABSTRACT Background: Dispersion of the QT interval is an electrocardiographic marker that can be useful in the stratification of arrhythmic risk in patients with acute myocardial infarction. Objective: To describe the influence of corrected QT interval dispersion in association with other risk factors as predictors of ventricular arrhythmias in acute myocardial infarction with ST-segment elevation. Methodology: 209 patients who entered consecutively with diagnosis of acute myocardial infarction with elevation of the ST segment from January 2013 to June 2014 at Camilo Cienfuegos General Provincial Hospital of Sancti Spíritus were studied prospectively. Clinical, electrocardiographic and echocardiographic laboratory data were collected; the prognostic implication of the corrected QT interval dispersion in the appearance of ventricular arrhythmias through binary logistic regression and operator-receiver curves was determined. Results: Ventricular arrhythmias occurred in 39 (18.7%) patients. The dispersion of the corrected QT showed an adequate discrimination capacity in the prediction of any serious ventricular arrhythmic episode (c = 0.768, p = 0.0001). In the multivariate analysis, QT dispersion was an independent predictor of ventricular arrhythmias (OR = 7.075, 95% CI = 1.6-32.9, p = 0.009). Conclusions: The probability of presenting ventricular arrhythmias during acute myocardial infarction is greater when the dispersion of the QT interval is increased, so it is suggested that it should be a variable to be evaluated in the prognostic stratification of acute myocardial infarction.

Reduced cardiotoxicity and increased oral efficacy of artemether polymeric nanocapsules in Plasmodium berghei-infected mice.

Artemether (ATM) cardiotoxicity, its short half-life and low oral bioavailability are the major limiting factors for its use to treat malaria. The purposes of this work were to study free-ATM and ATM-loaded poly-ε-caprolactone nanocapules (ATM-NC) cardiotoxicity and oral efficacy on Plasmodium berghei-infected mice. ATM-NC was obtained by interfacial polymer deposition and ATM was associated with polymeric NC oily core. For cardiotoxicity evaluation, male black C57BL6 uninfected or P. berghei-infected mice received, by oral route twice daily/4 days, vehicle (sorbitol/carboxymethylcellulose), blank-NC, free-ATM or ATM-NC at doses 40, 80 or 120 mg kg-1. Electrocardiogram (ECG) lead II signal was obtained before and after treatment. For ATM efficacy evaluation, female P. berghei-infected mice were treated the same way. ATM-NC improved antimalarial in vivo efficacy and reduced mice mortality. Free-ATM induced significantly QT and QTc intervals prolongation. ATM-NC (120 mg kg-1) given to uninfected mice reduced QT and QTc intervals prolongation 34 and 30%, respectively, compared with free-ATM. ATM-NC given to infected mice also reduced QT and QTc intervals prolongation, 28 and 27%, respectively. For the first time, the study showed a nanocarrier reducing cardiotoxicity of ATM given by oral route and it was more effective against P. berghei than free-ATM as monotherapy.

Factores de riesgo asociados a síndrome QT largo en anestesia cardiovascular / Risk factors associated with long QT syndrome in cardiovascular anesthesia

Introducción: el síndrome de QT largo es una canalopatía caracterizada por una grave alteración en la repolarización ventricular. Objetivo: determinar los factores de riesgo asociados a intervalo QT prolongado en anestesia cardiovascular. Métodos: estudio descriptivo, de corte transversal desde mayo de 2014 a mayo de 2016, en pacientes programados para cirugía cardíaca bajo circulación extracorpórea. Se evaluó el riesgo atribuible y el intervalo de confianza para un 95 por ciento en variables con p< 0,05. Resultados: se incluyeron 483 pacientes, con una edad media de 62 años, de ellos 57 (12 por ciento) registraron un QTc prolongado. La edad avanzada (RA: 1,8; IC 95 por ciento: 0,86-2,67), insuficiencia renal crónica (RA: 2,7; IC 95 por ciento: 0,82-4,96), diabetes mellitus tipo 2 (RA: 1,7; IC 95 por ciento: 1,01-2,15), cardiopatía isquémica (RA: 3,5; IC 95 por ciento: 1,60-4,02), hipertrofia ventricular izquierda (RA: 2,2; IC 95 por ciento: 2,53-3,15), anticálcicos (RA: 1,5; IC 95 por ciento: 0,92-2,98), anestesia general orotraqueal balanceada (RA: 2,1; IC 95 por ciento: 2,92-2,35), ondansetrón (RA: 1,7; IC 95 por ciento: 0,98-2,74), droperidol (RA: 1,8; IC 95 por ciento: 2,18-3,94), tiempo de circulación extracorpórea (RA: 2,5; IC 95 por ciento: 1,02-3,62), hipopotasemia (RA: 1,4; IC 95 por ciento: 1,03-2,91) y la bradicardia severa (RA: 1,8; IC 95 por ciento: 1,12-3,86) fueron asociados con alto riesgo de prolongación del intervalo QT. Las complicaciones fueron mayores en este grupo, con una mortalidad de 23 por ciento. Conclusiones: la edad avanzada, la insuficiencia renal crónica, diabetes mellitus tipo 2, hipertrofia ventricular y la cardiopatía isquémica facilitan la prolongación del QT inducida por los bloqueadores del calcio. El mayor tiempo de circulación extracorpórea, la anestesia balanceada con isoflurano, el uso de droperidol y ondansetrón, la bradicardia e hipopotasemia posoperatoria son variables asociadas con la extensión del intervalo QT, con un incremento en las complicaciones. Las taquiarritmias ventriculares y la mortalidad fueron mayores en este subgrupo de pacientes(AU)

Introduction: The long QT syndrome is a channelopathy characterized by a serious alteration in ventricular repolarization. Objective: To determine the risk factors associated with prolonged QT interval in cardiovascular anesthesia. Methods: Descriptive, cross-sectional study from May 2014 to May 2016, in patients scheduled for cardiac surgery under extracorporeal circulation. The attributable risk and the confidence interval were evaluated for 95 percent and in variables with p value under 0.05. Results: 483 patients were included, with a mean age of 62 years, of whom 57 (12 percent) had prolonged QTc. Advanced age (RA: 1.8, 95 percent CI: 0.86-2.67), chronic renal failure (RA: 2.7, 95 percent CI: 0.82-4.96), type 2 diabetes mellitus (RA: 1.7, 95 percent CI: 1.01-2.15), ischemic heart disease (RA: 3.5, 95 percent CI: 1.60-4.02), left ventricular hypertrophy (RA: 2.2, 95 percent CI: 2.53-3.15), calcium-lactam antibiotics (RA: 1.5, 95 percent CI: 0.92-2.98), balanced orotracheal general anesthesia (RA: 2.1, 95 percent CI: 2.92-2.35), ondansetron (RA: 1.7, 95 percent CI: 0.98-2.74), droperidol (RA: 1.8, 95 percent CI: 2.18-3.94) ), extracorporeal circulation time (RA: 2.5, 95 percent CI: 1.02-3.62), hypokalemia (RA: 1.4, 95 percent CI: 1.03-2.91) and severe bradycardia (RA: 1.8, 95 percent CI: 1.12-3.86) were associated with a high risk of QT prolongation. The complications were more significant in this group, with a mortality of 23 percent. Conclusions: Advanced age, chronic renal failure, type 2 diabetes mellitus, ventricular hypertrophy, and ischemic heart disease facilitate the prolongation of QT induced by calcium blockers. The longer time of extracorporeal circulation, the balanced anesthesia with isoflurane, the use of droperidol and ondansetron, bradycardia and postoperative hypokalemia are variables associated with the extension of the QT interval, with an increase in complications. Ventricular tachyarrhythmias and mortality were higher in this subgroup of patients(AU)

QRS duration and dispersion for predicting ventricular arrhythmias in early stage of acute myocardial infraction. / Duración y dispersión del QRS para predecir arritmias ventriculares en las fases iniciales del infarto agudo de miocardio.

OBJECTIVE: To determine the relationship between QRS duration and dispersion and the occurrence of ventricular arrhythmias in early stages of acute myocardial infarction (AMI). DESIGN: A retrospective, longitudinal descriptive study was carried out. SETTING: Hospital General Universitario "Camilo Cienfuegos", Sancti Spíritus, Cuba. Secondary health care. PATIENTS OR PARTICIPANTS: A total of 209 patients diagnosed with ST-segment elevation AMI from January 2012 to June 2014. MAIN VARIABLES OF INTEREST: The duration and dispersion of the QT interval, corrected QT interval, and QRS complex were measured in the first electrocardiogram performed at the hospital. The presence of ventricular tachycardia/fibrillation was assessed during follow-up (length of hospital stay). RESULTS: Arrhythmias were found in 46 patients (22%); in 25 of them (15.9%), arrhythmias originated in ventricles, and were more common in those subjects with extensive anterior wall AMI, which was responsible for 81.8% of the ventricular fibrillations and more than half (57.1%) of the ventricular tachycardias. The widest QRS complexes (77.3±13.3 vs. 71.5±6.4ms; P=.029) and their greatest dispersion (24.1±16.2 vs. 16.5±4.8ms; P=.019) were found on those leads that explore the regions affected by ischemia. The highest values of all measurements were found in extensive anterior wall AMI, with significant differences: QRS 92.3±18.8ms, QRS dispersion 37.9±23.9ms, corrected QT 518.5±72.2ms, and corrected QT interval dispersion 94.9±26.8ms. Patients with higher QRS dispersion values were more likely to have ventricular arrhythmias, with cutoff points at 23.5ms and 24.5ms for tachycardia and ventricular fibrillation, respectively. CONCLUSIONS: Increased QRS duration and dispersion implied a greater likelihood of ventricular arrhythmias in early stages of AMI than increased duration and dispersion of the corrected QT interval.

Drug-induced QT Interval Prolongation in the Intensive Care Unit.

BACKGROUND: The most common acquired cause of Long QT syndrome (LQTS) is drug induced QT interval prolongation. It is an electrophysiological entity, which is characterized by an extended duration of the ventricular repolarization. Reflected as a prolonged QT interval in a surface ECG, this syndrome increases the risk for polymorphic ventricular tachycardia (Torsade de Pointes) and sudden death. METHOD: Bibliographic databases as MEDLINE and EMBASE, reports and drug alerts from several regulatory agencies (FDA, EMEA, ANMAT) and drug safety guides (ICH S7B, ICH E14) were consulted to prepare this article. The keywords used were: polymorphic ventricular tachycardia, adverse drug events, prolonged QT, arrhythmias, intensive care unit and Torsade de Pointes. Such research involved materials produced up to December 2017. RESULTS: Because of their mechanism of action, antiarrhythmic drugs such as amiodarone, sotalol, quinidine, procainamide, verapamil and diltiazem are associated to the prolongation of the QTc interval. For this reason, they require constant monitoring when administered. Other noncardiovascular drugs that are widely used in the Intensive Care Unit (ICU), such as ondansetron, macrolide and fluoroquinolone antibiotics, typical and atypical antipsychotics agents such as haloperidol, thioridazine, and sertindole are also frequently associated with the prolongation of the QTc interval. As a consequence, critical patients should be closely followed and evaluated. CONCLUSION: ICU patients are particularly prone to experience a QTc interval prolongation mainly for two reasons. In the first place, they are exposed to certain drugs that can prolong the repolarization phase, either by their mechanism of action or through the interaction with other drugs. In the second place, the risk factors for TdP are prevalent clinical conditions among critically ill patients. As a consequence, the attending physician is expected to perform preventive monitoring and ECG checks to control the QTc interval.