Efecto de los fármacos en la prolongación del QT y la aparición de muerte súbita en la COVID-19 / Effect of Drugs on QT Prolongation and Sudden Death in COVID-19

Introducción: Las evidencias científicas han demostrado que durante el período pandémico por la COVID-19 ha existido un incremento de la incidencia de muerte súbita cardiovascular, proporcional al incremento de los casos y a la letalidad por la enfermedad. Objetivos: Compilar información sobre los fármacos empleados en el tratamiento de la COVID-19 y sus posibles efectos en la prolongación del intervalo QT y la aparición de muerte súbita. Métodos: Se realizó una búsqueda de información a partir de las bases de datos PubMed, Medline y SciELO, en los idiomas español e inglés en el período de enero de 2020 a enero de 2023. Resultados: Los hallazgos más recientes sugieren que los factores relacionados con el tratamiento médico del paciente para sus enfermedades cardiovasculares previas, el empleo concomitante de drogas para otras comorbilidades, el ensayo de nuevas drogas que se investigan en la actualidad para el tratamiento de la enfermedad y el uso inadecuado de fármacos en complicaciones graves por la COVID-19, pueden ocasionar prolongación del intervalo QT y arritmias ventriculares tipo torsades de pointes, lo que puede conllevar a la aparición de muerte súbita. Conclusiones: Ha sido demostrado el efecto deletéreo de los fármacos en el tratamiento de la COVID-19 y sus posibles asociaciones a la terapéutica del paciente, en la prolongación del tiempo de repolarización ventricular cardíaca, cuya traducción eléctrica es un intervalo QT prolongado y su contribución a la génesis de arritmias malignas potencialmente fatales capaces de desencadenar un paro cardíaco y evolucionar a la muerte súbita(AU)

Scientific evidence has shown an increase in the incidence of sudden cardiovascular death during the COVID-19 pandemic period. This has been proportional to the increase in cases and mortality from the disease. Direct and indirect injury to the myocardium and vascular system allow to partially explain the statistics. Among the factors related to the medical treatment of the patient for previous cardiovascular diseases, it is the concomitant use of drugs for other comorbidities. The trial of new drugs for the treatment of this condition and the inappropriate use of drugs in serious complications from COVID-19 are currently being investigated. These can cause QT prolongation and torsades de pointes ventricular arrhythmias, which can lead to sudden death. Monitoring the QT interval is recommended, before and during treatment, in patients who come to the emergency room with a clinical condition suggestive of COVID-19. Additionally, modifiable factors favoring its prolongation should be evaluated. Decision-making in the application of therapeutic protocols in patients with COVID-19 with prolonged QTc at baseline, or with increased QTc after starting treatment, must go through the analysis of the risk/benefit ratio defined by a multi- and interdisciplinary team(AU)

Uncontrolled Diabetes with Underlying Structural Changes in the Atrioventricular Node / Diabetes no Controlada con Cambios Estructurales Subyacentes en el Nodo Atrioventricular

SUMMARY: Diabetic cardiomyopathy, characterized by diabetes mellitus (DM) -induced cardiac muscular abnormalities, is a strong inducer of impaired cardiac contraction and arrhythmia. Atrioventricular block, a serious type of arrhythmia resulting from interruption of cardiac impulse conduction via the atrioventricular node (AVN), frequently occurs among diabetic patients. However, details of structural changes in AVN in DM remain poorly explained. Here, this study defined the effects of DM on the morphological remodeling of the AVN in male Sprague Dawley rats induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight). At 24 weeks, the pathological changes in the AVN were assessed by light microscopy (LM) and transmission electron microscopy (TEM). Under LM, the AVN in diabetic rats became a less compact mass and exhibited the intracellular vacuolation. The nodal cells were more varied in sizes with the absence or shrinkage of nuclei and clear cytoplasm compared to the control. The collagen content significantly increased in relation to the presence of myofibroblasts. Consistent with LM, TEM images of the diabetic nodal cells revealed several signs of cell damage, such as mitochondrial changes, deterioration of cell organelles, gap junction internalization, and cell separation. Furthermore, changes in AVN innervation, evidenced by damaged Schwann cells and axons, were also found. These results indicated alterations in important components in the AVN during diabetic condition, which may lead to the impairment of electrical conduction, causing abnormal cardiac functions in diabetic patients.

La miocardiopatía diabética, caracterizada por anomalías musculares cardíacas inducidas por diabetes mellitus (DM), es un fuerte inductor de alteración de la contracción cardíaca y arritmia. El bloqueo atrioventricular, un tipo grave de arritmia resultante de la interrupción de la conducción del impulso cardíaco a través del nodo atrioventricular (NAV), se produce con frecuencia entre los pacientes diabéticos. Sin embargo, los detalles de los cambios estructurales en NAV en DM siguen estando pobremente explicados. Aquí, este estudio definió los efectos de la DM en la remodelación morfológica del NAV en ratas macho Sprague Dawley inducidas por inyección intraperitoneal de estreptozotocina (60 mg/kg de peso corporal). A las 24 semanas, los cambios patológicos en el NAV se evaluaron mediante microscopía óptica (MO) y microscopía electrónica de transmisión (MET). Bajo MO, el NAV en ratas diabéticas se convirtió en una masa menos compacta y exhibió la vacuolización intracelular. Las células nodales tenían tamaños más variados con ausencia o contracción de núcleos y citoplasma claro en comparación con el control. El contenido de colágeno aumentó significativamente en relación con la presencia de miofibroblastos. De acuerdo con MO, las imágenes MET de las células nodales diabéticas revelaron varios signos de daño celular, como cambios mitocondriales, deterioro de los orgánulos celulares, internalización de uniones comunicantes y separación celular. Además, también se encontraron cambios en la inervación del NAV, evidenciados por schwannocitos y axones dañados. Estos resultados indicaron alteraciones en componentes importantes en el NAV durante la condición diabética, lo que puede conducir al deterioro de la conducción eléctrica, causando funciones cardíacas anormales en estos pacientes.

Elaboração de algoritmo para interpretação rápidadas principais arritmias cardíacas no eletrocardiograma / Algorithm Elaboration For Quick Interpretation Of The Main Heart Arrythmias In The Electrocardiogram

Objetivo: relatar a elaboração de um algoritmo para facilitar a interpretação rápida das principais arritmias cardíacas no eletrocardiograma. Método: estudo descritivo, exploratório, com abordagem qualitativa, do tipo relato de experiência, realizado mediante um projeto de intervenção em educação em saúde durante o ano de 2021. Resultados: a elaboração do algoritmo denominado Scaritmo contribuiu para sistematizar as etapas de identificação de arritmias cardíacas, favorecendo o processo didático e aprendizado dos estudantes e otimizando a interpretação rápida do eletrocardiograma. Conclusão: o uso do algoritmo Scaritmo permite a sistematização teórico-prática das etapas necessárias para a interpretação do eletrocardiograma tornando sua avaliação mais didática e assertiva pelo examinador em treinamento.(AU)

Objective: to report the development of an algorithm to facilitate the rapid interpretation of the main cardiac arrhythmias in electrocardiogram. Method: a descriptive, exploratory study with qualitative approach, of experience report type, conducted through an intervention project in health education during the year 2021. Results: The development of the algorithm called Scaritmo contributed to systematize the steps of cardiac arrhythmia identification, favoring the didactic process and student learning, and optimizing the rapid interpretation of the electrocardiogram. Conclusion: The use of the Scaritm algorithm allows the theoretical and practical systematization of the steps necessary for the interpretation of electrocardiograms, making its evaluation more didactic and assertive by the examiner in training.(AU)

Objetivo: relatar el desarrollo de un algoritmo para facilitar la interpretación rápida de las principales arritmias cardíacas en electrocardiograma. Método: estudio descriptivo, exploratorio, con abordaje cualitativo, de tipo relato de experiencia, realizado a través de un proyecto de intervención en educación para la salud durante el año 2021. Resultados: el desarrollo del algoritmo denominado Scaritmo contribuyó para sistematizar los pasos de identificación de arritmias cardíacas, favoreciendo el proceso didáctico y el aprendizaje de los alumnos y optimizando la rápida interpretación del electrocardiograma. Conclusión: El uso del algoritmo Scaritmo permite la sistematización teórica y práctica de los pasos necesarios para la interpretación del electrocardiograma, tornando su evaluación más didáctica y asertiva por el examinador en formación.(AU)

CD38: rol en la electrofisiología cardíaca normal y en arritmias por isquemia y reperfusión / CD38: role in normal cardiac electrophysiology and in arrhythmias due to ischemia and reperfusion

Introducción: CD38 es una glicoproteína transmembrana de 300 aminoácidos y 45 kDa expresada de forma ubicua en el organismo que cumple importantes funciones en el metabolismo del cofactor NAD+ y en la regulación del movimiento del calcio celular. Uno de los productos enzimáticos de CD38 es el adenosín difosfato ribosa cíclico o ADP-ribosil cíclico (ADPRc), que actúa como segundo mensajero sensibilizando la liberación de calcio inducida por calcio (CICR por su sigla en inglés). En las últimas 3 décadas se han hecho esfuerzos en la investigación del papel de esta enzima en el sistema cardiovascular, sin embargo aún resta mucho por saber. Antecedentes: Los primeros estudios sobre el papel de CD38/ADPRc a nivel miocárdico mostraron un efecto potenciador del transitorio del calcio por parte del ADPRc. Además se ha descrito un papel arritmogénico utilizando distintas técnicas tanto en modelos reduccionistas como en organismos de mamíferos in vivo. Entre ellos se encuentran modelos de ratones Knock Out para CD38 (CD38KO). La enzima forma parte de la vía de señalización adrenérgica a través de la producción de ADPRc, y se la ha vinculado también a procesos patológicos relacionados con hipertrofia ventricular e isquemia miocárdica. Por ejemplo, la inhibición de la actividad de CD38 protegería al corazón contra la injuria por isquemia y reperfusión (I-R) in vivo e in vitro, disminuyendo el área de infarto. Nuestro grupo ha estado estudiando el rol de CD38 en la actividad cardíaca. Hemos reportado alteraciones en el manejo del Ca++ en miocitos ventriculares aislados de ratones CD38KO, y, en ratones CD38KO in vivo, menor frecuencia cardíaca (FC), marcada variabilidad de la FC, así como menor incidencia de arritmias ventriculares ante un estímulo suprafisiológico de cafeína/adrenalina. No obstante, no se ha investigado su papel en las arritmias por isquemia y reperfusión (I-R) teniendo en cuenta la conocida sobrecarga celular de calcio en este contexto y sabiendo que es la principal causa de muerte súbita en la población general. Tampoco sabemos cómo contribuye a la electrofisiología miocárdica en condiciones fisiológicas, específicamente a la morfología del potencial de acción miocárdico (PA) o a la morfología del trazado electrocardiográfico (ECG). Objetivo: Analizar el papel de CD38 en la actividad eléctrica miocárdica estudiando desde el PA celular hasta el ECG de superficie y su posible impacto en arritmias ventriculares producidas por isquemia y reperfusión. Estrategia: Para el desarrollo de la tesis trabajé con modelos de ratones salvajes (wild type, WT) y CD38KO tanto in vivo como in vitro. Estudié el corazón aislado y perfundido mediante el sistema Langendorff realizando registro extracelular (EMG) e intracelular (potencial de acción, PA). Realicé una caracterización de la morfología del PA midiendo la duración al 30% (APD30) y al 90% (APD90) de la repolarización. Comparé entre las cepas WT y CD38KO con y sin estimulo adrenérgico y en la cepa WT entre estado control y ante la inhibición de CD38 con 78c, un fármaco inhibidor de la actividad enzimática de CD38. Para comparar el potencial arritmogénico de los corazones de ambas cepas a la injuria provocada por I-R registré la actividad eléctrica espontánea mediante EMG, en condiciones basales, durante isquemia global y reperfusión. En el modelo in vivo analicé el ECG de ratones WT y CD38KO anestesiados y comparé la actividad basal y la respuesta arrítmica ante un modelo de infarto de miocardio por sobrecarga adrenérgica con isoproterenol. Resultados y discusión: Describí por primera vez la morfología del PA en la cepa CD38KO y no fue distinta a la de los ratones salvajes en condiciones basales. Esta falta de diferencias podría deberse a compensaciones fisiológicas que ocurren ante la carencia de la enzima como el aumento en la expresión de la bomba SERCA2a. Por lo contrario, cuando sometí el preparado a un desequilibrio homeostático estimulando con un agonista beta adrenérgico, la APD90 de los corazones CD38KO no disminuyó como la de los WT. En concordancia, la inhibición aguda de CD38 en el PA miocárdico de corazones WT perfundidos con 78c aumentó la APD90 significativamente sin cambios en el APD30. Cuando sometí a los corazones CD38KO aislados a un medio arritmogénico con alto contenido de calcio y bajo en potasio, la FC en estos no aumentó a diferencia de lo que ocurrió marcadamente en los WT. La respuesta arrítmica ante la isquemia global en el corazón aislado no fue menor en la cepa CD38KO a diferencia de lo esperado, mostrando una incidencia de 57 % en los WT y 75 % en los CD38KO (valor p = 0.61). En el modelo in vivo describí por primera vez el trazado electrocardiográfico (DII) de animales carentes de CD38. No hubo diferencias en la FC, intervalo PR, intervalo QT, amplitud de onda S, ni amplitud de onda T. Sin embargo la duración del QRS fue menor, mientras que la amplitud de la onda R fue mayor en los ratones CD38KO, probablemente secundario a una mayor velocidad de conducción. Estas diferencias se perdieron en la etapa aguda de la isquemia por sobrecarga adrenérgica. En la cepa CD38KO como era esperado vi mayor proporción de pausas sinusales, que se hicieron más evidentes ante la injuria por isoproterenol, lo que podría estar evidenciando una mayor refractariedad del CICR por disminución del contenido de calcio reticular. No se demostró la protección ante arritmias generadas por isquemia en la cepa CD38KO ya que el incremento de la carga arrítmica fue similar en ambas cepas. No hubo diferencias significativas en la proporción de ratones afectados ni en la suma total de extrasístoles ventriculares registradas pero la mortalidad que generó la sobrecarga adrenérgica en el grupo WT fue de 1/3 mientras que la totalidad de los ratones CD38KO sobrevivieron. Conclusiones: En esta tesis presento una caracterización electrofisiológica de CD38 desde el PA en corazón entero hasta la manifestación electrocardiográfica de superficie, con una evaluación especial de su papel en arritmias por I-R y desarrollando técnicas innovadoras a nivel nacional. Las principales conclusiones son: CD38: rol en la electrofisiología cardíaca normal y en arritmias por isquemia y reperfusión 12 - CD38 contribuye a la repolarización tardía disminuyendo el APD90. - La ausencia de la enzima evita el aumento de la FC en un medio arritmogénico con sobrecarga de Ca++ . - CD38 contribuye con un enlentecimiento en la velocidad de conducción miocárdica manifiesta en un descenso de la duración y aumento del voltaje del QRS en los corazones de ratones que no expresan CD38La deleción de CD38 genera un aumento marcado de pausas sinusales ante la isquemia. - No hay evidencia de una protección ante arritmias malignas por I-R in vitro mediante la deleción de CD38. - No se vio una contribución de CD38 a arritmias malignas por isquemia in vivo aunque la ausencia de la enzima parece mejorar el perfil de supervivencia.

Une double discordance cardiaque complexe décompensée, à propos d'un cas et revue de la littérature / A double cardiac discordance decompensated, about a case and review of the literature

La double discordance est une cardiopathie congénitale complexe extrêmement rare, elle se caractérise par une discordance auriculo-ventriculaire suivie d'une autre discordance ventriculo-artérielle. Son diagnostic est posé généralement à l'âge adulte par des examens d'imagerie. Son pronostic dépend essentiellement des autres malformations congénitales cardiaques associées, des arythmies et des troubles de la conduction, ainsi que de la fonction systolique du ventricule droit en position systémique. Nous rapportons le cas d'un patient âgé de 23 ans, porteur d'une cardiopathie congénitale complexe cyanogène. Il s'agit d'une double discordance associée à une large communication interventriculaire sous aortique avec un shunt inversé et une hypoplasie de l'artère pulmonaire. Ce diagnostic a été confirmé par l'imagerie multimodale. Non opéré, le patient a vu son stade fonctionnel s'aggraver rapidement avec une dyspnée qui est passée d'un stade I à un stade III-IV de la New York Heart Association (NYHA), et apparition de signes hypoxiques et congestifs. A travers cette observation, nous avons précisé les caractéristiques anatomocliniques de cette cardiopathie congénitale complexe cyanogène, son exploration, ses options thérapeutiques, ainsi que le rôle péjoratif de son association avec d'autres malformations congénitales.

Double discordance is an extremely rare complex congenital heart disease; It is characterized by atrioventricular discordance followed by another ventriculo-arterial discordance. Its diagnosis is usually made in adulthood by imaging examinations. Its prognosis depends mainly on other associated congenital heart defects, arrhythmias and disorders of the conduction, as well as systolic function of the right ventricle in the systemic position. We report the case of a 23-year-old patient with a complex cyanogen heart disease.It is a double discordance associated to an interventricular communication with reverse shunt and an hypoplasia of the pulmonary artery.This Diagnosis was confirmed in multimodal imaging. Non-operated, the patient saw his functional status worsen rapidly with dyspnea which went from stage I to stage III-IV of the New York Heart Association (NYHA), and appearance of hypoxic and congestive signs. Through this observation, we have clarified the anatomoclinical characteristics of this complex congenital cyanogens heart disease, the necessary explorations and the different therapeutic options, as well as the pejorative role of its association with other congenital malformations.

Anomalies électrocardiographiques chez les patients hospitalisés pour COVID-19 à Fianarantsoa, Madagascar

Les anomalies électrocardiographiques sont l'expression d'une atteinte cardiovasculaire lors de la COVID-19. Les troubles du rythme et de la conduction cardiaque peuvent mettre en jeu le pronostic vital à court terme au cours de la COVID -19. Notre objectif principal est de décrire les anomalies électrocardiographiques et leurs fréquences chez les patients atteints de la COVID -19. L'objectif secondaire est de déterminer l'association entre ces anomalies électrocardiographiques et la gravité de la maladie. Méthodes : Il s'agit d'une étude rétrospective à visée descriptive des patients hospitalisés pour COVID-19 dans les centres de traitement COVID -19 de Fianarantsoa sur une période de 14 mois. Résultats : Nous avons retenu 101 patients. Le sex-ratio était de 1,06. La moyenne d'âge était de 59,81ans +/- 11,9. Tous les patients retenus avaient un électrocardiogramme à 12 dérivations et un test positif à la COVID-19. L'électrocardiogramme (ECG) était anormal chez 87 (86,1%) patients. Dans les formes graves et modérées de la maladie nous avons enregistré à l'ECG: 51 (50,5%) tachycardies sinusales, 13 (12,8%) blocs de branche incomplets droits, 13 (12,8%) profil S1Q3T3, 24 (23,7%) ondes Q pathologiques, 19 (18,8%) anomalies du segment ST. Dans les formes graves de la maladie nous avons enregistré à l'ECG: 2 (3,8%) bloc auriculoventriculaire complet (BAV complet), 7 (13,4%) blocs de branche gauche complet (BBG), 5 (9,6%) blocs de branche droit complet (BBD). La tachycardie sinusale avait une association significative avec la gravité de la maladie (p=0,002). Conclusion : Des anomalies électrocardiographiques ont été observées dans notre étude. La tachycardie sinusale était associée à la gravité de la maladie. Une surveillance rythmique, des explorations cardiaques plus pertinentes sont nécessaires pour une meilleure prise charge de la COVID-19

Suxiao Jiuxin Pills Prevent Ventricular Fibrillation from Inhibiting L-type Calcium Currents CaV1.2 in vivo and in vitro / 中国结合医学杂志

OBJECTIVE@#To investigate whether Suxiao Jiuxin Pills (SJP), a Chinese herbal remedy, is an anti-ventricular fibrillation (VF) agent.@*METHODS@#VF was induced by isoproterenolol (ISO) intraperitoneal injection followed by electrical pacing in mice and rabbits. The effects of SJP on the L-type calcium channel current (CaV1.2), voltage-dependent sodium channel current (INa), rapid and slow delayed rectifier potassium channel current (IKr and IKs, respectively) were studied by whole-cell patch-clamp method. Computer simulation was implemented to incorporate the experimental data of SJP effects on the CaV1.2 current into the action potential (AP) and pseudo-electrocardiography (pseudo-ECG) models.@*RESULTS@#SJP prevented VF induction and reduced VF durations significantly in mice and rabbits. Patch-clamp experiments revealed that SJP decreased the peak amplitude of the CaV1.2 current with a half maximal concentration (IC50) value of 16.9 mg/L (SJP-30 mg/L, -32.8 ± 6.1 pA; Verapamil, -16.2 ±1.8 pA; vs. control, -234.5 ±16.7 pA, P<0.01, respectively). The steady-state activation curve, inactivation curve, and the recovery from inactivation of the CaV1.2 current were not shifted significantly. Specifically, SJP did not altered INa, IKr, and IKs currents significantly (SJP vs. control, P>0.05). Computer simulation showed that SJP-reduced CaV1.2 current shortened the AP duration, transiting VF into sinus rhythm in pseudo-ECG.@*CONCLUSION@#SJP reduced VF via inhibiting the CaV1.2 current with in vivo, in vitro, and in silico studies, which provide experimental basis for SJP anti-VF clinical application.

Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury / 中华医学杂志(英文版)

BACKGROUND@#Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.@*METHODS@#Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements.@*RESULTS@#Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.@*CONCLUSION@#PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.

One case of myocardial damage caused by carbamate pesticide poisoning / 中华劳动卫生职业病杂志

The data of a patient with carbamate pesticide poisoning were analyzed. Cardiac arrest, oliguria, acute renal injury and pulmonary infection occurred during treatment. After cardiopulmonary resuscitation, tracheal intubation, CRRT, anti-infection and other symptomatic support treatment, the patient recovered and discharged. The myocardial damage caused by carbamate pesticide poisoning is easy to be ignored, and it often causes cardiac manifestations such as arrhythmia and cardiac insufficiency, and the related markers of cardiac injury, electrocardiogram and echocardiogram are also changed. Therefore, the awareness of cardiac damage caused by carbamate pesticide poisoning should be improved.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Intraoperative management of potentially fatal arrhythmias after anesthesia induced by severe hypokalemia: A case report / 北京大学学报(医学版)

Severe hypokalemia is defined as the concentration of serum potassium lower than 2.5 mmol/L, which may lead to serious arrhythmias and cause mortality. We report an unusual case of potentially fatal ventricular arrhythmias induced by severe hypokalemia in a patient undergoing laparoscopic partial nephrectomy in Peking University Third Hospital due to irregular use of indapamide before operation. Indapamide is a sulfonamide diuretic with vasodilative and calcium antagonistic effects, which enhances sodium delivery to the renal distal tubules resulting in a dose-related increase in urinary potassium excretion and decreases serum potassium concentrations. The electrolyte disorder caused by the diuretic is more likely to occur in the elderly patients, especially those with malnutrition or long-term fasting. Hence, the serum potassium concentration of the patients under indapamide therapy, especially elderly patients, should be monitored carefully. Meanwhile, the potassium concentration measured by arterial blood gas analysis is different from that measured by venous blood or laboratory test. According to the previous research, the concentration of potassium in venous blood was slightly higher than that in arterial blood, and the difference value was 0.1-0.5 mmol/L. This error should be taken into account when rapid intravenous potassium supplementation or reduction of blood potassium level was carried out clinically. In the correction of severe hypokalemia, the standard approach often did not work well for treating severe hypokalemia. The tailored rapid potassium supplementation strategy shortened the time of hypokalemia and was a safe and better treatment option to remedy life-threatening arrhythmias caused by severe hypokalemia with a high success rate. Through the anesthesia management of this case, we conclude that for the elderly patients who take indapamide or other potassium excretion diuretics, the electrolyte concentration and the general volume state of the patients should be comprehensively measured and fully evaluated before operation. It may be necessary for us to reexamine the serum electrolyte concentration before anesthesia induction on the morning of surgery in patients with the history of hypokalemia. For severe hypokalemia detected after anesthesia, central venous cannulation access for individualized rapid potassium supplementation is an effective approach to reverse the life-threatening arrhythmias caused by severe hypokalemia and ensure the safety of the patients.

Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine / 中西医结合学报

OBJECTIVE@#The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.@*METHODS@#The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.@*RESULTS@#Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.@*CONCLUSION@#Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.

Chinese emergency expert consensus on bedside temporary cardiac pacing (2023) / 中华危重病急救医学

Temporary cardiac pacing is an essential technique in the diagnosis and treatment of arrhythmias. Due to its urgency, complexity, and uncertainty, it is necessary to develop an evidence-based emergency operation norms. Currently, there is no specific consensus guidelines at home or abroad. The Emergency Branch of Chinese Medical Association organized relevant experts to draft the Chinese emergency expert consensus on bedside temporary cardiac pacing (2023) to guide the operation and application of bedside cardiac pacing. The formulation of the consensus adopts the consensus meeting method and the evidentiary basis and recommendation grading of the Oxford Center for Evidence-based Medicine in the United States. A total of 13 recommendations were extracted from the discussion on the methods of bedside temporary cardiac pacing, the puncture site of transvenous temporary cardiac pacing, the selection of leads, the placement and placement of leads, pacemaker parameter settings, indications, complications and postoperative management. The recommended consensus includes the choice between transcutaneous and transvenous pacing, preferred venous access for temporary transvenous pacing, the target and best guidance method for implantation of bedside pacing electrodes, recommended default pacemaker settings, recommended indications for sinoatrial node dysfunction, atrioventricular block, acute myocardial infarction, cardiac arrest, ventricular and supraventricular arrhythmias. They also recommended ultrasound guidance and a shortened temporary pacing support time to reduce complications of temporary transvenous cardiac pacing, recommended bedrest, and anticoagulation after temporary transvenous pacing. Bedside temporary cardiac pacing is generally safe and effective. Accurate assessment, correct selection of the pacing mode, and timely performance of bedside temporary cardiac pacing can further improve the survival rate and prognosis of related emergency patients.

Summary of evidence for threshold setting of multi-parameter electrocardiograph monitor in intensive care unit / 中华危重病急救医学

OBJECTIVE@#To retrieve the evidence for threshold setting of multi-parameter electrocardiograph (ECG) monitors in intensive care unit (ICU), and summarize the best evidence.@*METHODS@#After literature retrieval, clinical guidelines, expert consensus, evidence summary and systematic review that met the requirements were screened. Guidelines were evaluated by the appraisal of guidelines for research and evaluation II (AGREE II), expert consensus and systematic review were evaluated by the Australian JBI evidence-based health care center authenticity evaluation tool, and evidence summary was evaluated by the CASE checklist. High-quality literature was selected to extract evidence related to the use and setup of multi-parameter ECG monitors in the ICU.@*RESULTS@#A total of 19 literatures were included, including 7 guidelines, 2 expert consensus, 8 systematic reviews, 1 evidence summary, and 1 national industry standard. After evidence extraction, translation, proofreading and summary, a total of 32 pieces of evidence were integrated. The included evidence involved the environmental preparation for the application of the ECG monitor, the electrical requirements of the ECG monitor, ECG monitor use process, ECG monitor alarm setting principles, ECG monitor alarm heart rate or heart rhythm monitoring setting, ECG monitor alarm blood pressure monitoring setting, ECG monitor alarm respiratory and blood oxygen saturation threshold setting, alarm delay warning time setting, adjusting alarm setting method, evaluating alarm setting time, improving the comfort of monitoring patients, reducing nuisance alarm report the occurrence, alarm priority processing, alarm intelligent processing and so on.@*CONCLUSIONS@#This summary of evidence involves many aspects of the setting and application of ECG monitor. According to the latest guidelines and expert consensus, it is updated and revised to guide healthcare workers to monitor patients more scientifically and safely, and aims to ensure patient safety.

Intelligent Electrocardiogram Analysis in Medicine: Data, Methods, and Applications / 中国医学科学杂志(英文版)

Electrocardiogram (ECG) is a low-cost, simple, fast, and non-invasive test. It can reflect the heart's electrical activity and provide valuable diagnostic clues about the health of the entire body. Therefore, ECG has been widely used in various biomedical applications such as arrhythmia detection, disease-specific detection, mortality prediction, and biometric recognition. In recent years, ECG-related studies have been carried out using a variety of publicly available datasets, with many differences in the datasets used, data preprocessing methods, targeted challenges, and modeling and analysis techniques. Here we systematically summarize and analyze the ECG-based automatic analysis methods and applications. Specifically, we first reviewed 22 commonly used ECG public datasets and provided an overview of data preprocessing processes. Then we described some of the most widely used applications of ECG signals and analyzed the advanced methods involved in these applications. Finally, we elucidated some of the challenges in ECG analysis and provided suggestions for further research.

An image classification method for arrhythmias based on Gramian angular summation field and improved Inception-ResNet-v2 / 生物医学工程学杂志

Arrhythmia is a significant cardiovascular disease that poses a threat to human health, and its primary diagnosis relies on electrocardiogram (ECG). Implementing computer technology to achieve automatic classification of arrhythmia can effectively avoid human error, improve diagnostic efficiency, and reduce costs. However, most automatic arrhythmia classification algorithms focus on one-dimensional temporal signals, which lack robustness. Therefore, this study proposed an arrhythmia image classification method based on Gramian angular summation field (GASF) and an improved Inception-ResNet-v2 network. Firstly, the data was preprocessed using variational mode decomposition, and data augmentation was performed using a deep convolutional generative adversarial network. Then, GASF was used to transform one-dimensional ECG signals into two-dimensional images, and an improved Inception-ResNet-v2 network was utilized to implement the five arrhythmia classifications recommended by the AAMI (N, V, S, F, and Q). The experimental results on the MIT-BIH Arrhythmia Database showed that the proposed method achieved an overall classification accuracy of 99.52% and 95.48% under the intra-patient and inter-patient paradigms, respectively. The arrhythmia classification performance of the improved Inception-ResNet-v2 network in this study outperforms other methods, providing a new approach for deep learning-based automatic arrhythmia classification.

Antiarrhythmic active components in traditional Chinese medicine acting on potassium channels / 中国中药杂志

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.

Clinical application of Chaihu Jia Longgu Muli Decoction based on modern pathophysiology mechanism / 中国中药杂志

Chaihu Jia Longgu Muli Decoction was firstly recorded in Treatise on Cold Damage(ZHANG Zhong-jing, Eastern Han dynasty). According to this medical classic, it is originally used in the treatment of the Shaoyang and Yangming syndrome. Based on the modern pathophysiological mechanism, this study interpreted the classic provisions of Chaihu Jia Longgu Muli Decoction. Original records of "chest fullness" "annoyance" "shock" "difficult urination" "delirium" "heavy body and failing to turn over" all have profound pathophysiological basis, involving disorders in cardiovascular, respiratory, nervous, and mental systems. This formula is widely used, which can be applied to treat epilepsy, cerebral arteriosclerosis, cerebral infarction, and other cerebrovascular diseases, hypertension, arrhythmia, and other cardiovascular diseases, insomnia, constipation, anxiety, depression, cardiac neurosis and other acute and chronic diseases as well as diseases in psychosomatic medicine. The clinical indications include Bupleuri Radix-targeted syndrome such as fullness and discomfort in chest and hypochondrium, bitter taste mouth, dry throat, and dizziness, the insomnia, anxiety, depression, susceptibility to fright, upset, dreamfulness and other psychiatric symptoms, red tongue, thick and yellow tongue coating, and wiry hard and powerful pulse. This formula was found to be used in combination with other formulas, such as Gualou Xiebai Decoction, Wendan Decoction, Zhizhu Pills, Juzhijiang Decoction, Suanzaoren Decoction, and Banxia Baizhu Tianma Decoction.

Arrhythmia:innovative understanding from traditional Chinese medicine and treatment by classic herbal formulas / 中国中药杂志

Arrhythmia, a common and frequently occurring cardiovascular disease, causes a heavy burden on the public health of China. Approximately 20 million patients are suffering from this disease in China and treated by pharmacological and surgical therapies. However, antiarrhythmic drugs can cause arrhythmia and surgical treatment has the risks of failure and recurrence. Therefore, the clinical outcome of arrhythmia remains to be improved. According to the traditional Chinese medicine(TCM) theory, arrhythmia is a disease of palpitation induced by 7 conditions: liver depression and Qi stagnation, accumulation of turbid phlegm, fluid retention attacking the heart, fire-heat disturbing the heart, stasis obstruction of heart vessel, cold congealing in heart vessel, and the deficiency of Qi, blood, Yin, and Yang. Therefore, this study concisely proposed 7 TCM syndromes of arrhythmia, including the palpitation due to depression, phlegm, fluid retention, fire, blood stasis, cold, and deficiency. The corresponding treatment strategies were recommended as follows: Chaihu Longgu Muli Decoction for the palpitation due to depression, Wendan Decoction for the palpitation due to phlegm, Linggui Zhugan Decoction for the palpitation due to fluid retention, Sanhuang Xiexin Decoction for the palpitation due to fire, Xuefu Zhuyu Decoction for the palpitation due to blood stasis, and Mahuang Fuzi Xixin Decoction for the palpitation due to cold, and Guizhi Gancao Decoction, Guizhi Gancao Longgu Muli Decoction, Huanglian Ejiao Decoction, Zhigancao Decoction, and Guipi Decoction for the palpitation due to the deficiency of Qi, blood, Yin, and Yang. Multiple formulas should be combined if the patient presents several TCM syndromes simultaneously. According to the principles of the correspondence between formula and syndrome and the treatment with consideration to both pathogenesis and pathology and both herbal nature and pharmacology, this study proposed an integrated treatment model of "pathogenesis-pathology-nature-pharmacology" to enhance the clinical efficacy of classic herbal formulas in the treatment of arrhythmia.

Zhenwu Decoction:connotation interpretation based on severe cases and modern pathophysiological mechanisms and application in treatment of heart failure in critical care unit / 中国中药杂志

Zhenwu Decoction is recorded in Treatise on Febrile Diseases by an outstanding physician ZHANG Zhong-jing in the Han dynasty. With effect of warming yang, transforming Qi, and promoting urination, Zhenwu Decoction is mainly used to treat edema due to yang deficiency. The studies of the severe and critical cases and the pathophysiological mechanisms have demonstrated that the record of Zhenwu Decoction in Treatise on Febrile Diseases describes the clinical symptoms and therapeutic regimen of acute heart failure. The syndrome treated by this formula may be related to the misdiagnosis and wrong treatment. Due to the difficult distinguishing between cardiogenic dyspnea and pulmonary dyspnea, high doses of Ephedrae Herba may be misused for inducing sweating, which may finally lead to the acute aggravation of heart failure, electrolyte disorder, and pulmonary infection. The syndrome treated by Zhenwu Decoction can illustrate the lack of experience of ancient physicians in treating acute heart failure. The description of "trembling and shivering" may be the clinical manifestation of heart failure, which is an upgraded version of "trembling and shaking" treated by Linggui Zhugan Decoction.(1)In terms of diseases, Zhenwu Decoction is suitable for the treatment of acute or chronic heart failure, cardiorenal syndrome, and diuretic resistance. The decoction is especially suitable for treating whole heart failure, acute heart failure, heart failure with reduced ejection fraction, and heart failure with the syndrome of sold and dampness. In addition, it can be used to treat both type Ⅱ and type Ⅳ cardiorenal syndrome.(2)In terms of symptoms, Zhenwu Decoction can be used for treating chest tightness, palpitations, lower limb edema, difficult urination or increased urine output, fear of cold, pale fat tongue with teeth marks, white and slippery tongue fur, and deep or slow pulse.(3)In terms of the pharmacological mechanism, Zhenwu Decoction treats heart failure following the principle of promoting urination, expanding blood vessels, and invigorating heart in modern medicine. Aconiti Lateralis Radix Praparata is the sovereign herb in the formula, with the recommended dosage of 30-60 g. However, arrhythmia may be caused by high doses of Aconiti Lateralis Radix Praparata, which should be used with concern. In addition to Zhenwu Decoction, Shenqi Pills, Renshen Decoction, Wuling Powder, and Fangji Huangqi Decoction with the effect of invigorating spleen, replenishing Qi, warming Yang, and promoting urination can be used in the recovery stage. The therapy of reinforcing Yang was the last choice for critical cases due to the lack of medical conditions, unclear clinical diagnosis in history, which should be treated objectively now.