Bloqueo de rama alternante: reporte de una complicación inusual tras implante valvular aórtico transcatéter / Alternating bundle branch block: report of an unusual complication after transcatheter aortic valve implantation

Resumen Los trastornos de la conducción representan una potencial complicación de los reemplazos valvulares percutáneos. Los bloqueos alternantes de rama, aunque son inusuales, reflejan daño extenso del sistema His Purkinje con riesgo potencial de bloqueo auriculoventricular completo, por lo cual es importante su identificación y abordaje oportuno. Se presenta el caso de una paciente femenina de 82 años con múltiples comorbilidades y estenosis aórtica severa, en seguimiento médico desde hacía un año, en quien no se había realizado reemplazo quirúrgico por negativa de la paciente y por el alto riesgo intraoperatorio. Ingresó a la institución con un cuadro clínico de disnea progresiva de un mes de evolución, se realizó ecocardiograma transtorácico documentando estenosis aórtica crítica y fue llevada a implante valvular aórtico percutáneo. Por el alto riesgo de necesidad de marcapasos peri o postprocedimiento, se realizó seguimiento con monitoreo Holter, documentando bloqueo alternante de rama, el cual no progresó a bloqueo auriculoventricular completo luego de 72 horas de seguimiento, por lo que no se implantó marcapasos permanente. MÉD.UIS.2020;33(3): 37-42

Abstract Conduction disorders represent a potential complication of percutaneous valve replacements. Alternating bundle branch block, although unusual, reflect extensive damage of the His-Purkinje system with potential risk of complete atrioventricular block, therefore, its identification and timely approach is important. We present the case of an 82 years old female patient with multiple comorbidities and a medical history of severe aortic stenosis in medical follow-up for a year, in whom surgical replacement had not been conducted due to the patient's refusal and to the high surgical risk. She was admitted to the institution referring one month of progressive shortness of breath and an echocardiogram documented critical aortic stenosis. Percutaneous aortic valve implantation was performed. Due to her high risk of needing a peri or post-procedure pacemaker, Holter monitoring was performed, documenting alternating bundle branch block, which did not progress to complete atrioventricular block after 72 hours of follow-up, in consequence, a permanent pacemaker was not implanted. MÉD.UIS.2020;33(3): 37-42

Cardiac conduction defects and complete heart block in myotonic dystrophy / Defectos de conduccion cardiaca y bloqueo cardiaco completo en la distrofìa miotonica

Classic myotonic dystrophy is a multisystem disorder that results from RNA toxicity and is one of the commonest adult onset muscular dystrophies. Patients often present with muscle stiffness from myotonia and dysphagia or dysarthria from laryngopharyngoesophageal muscle weakness. Benign electrocardiogram changes such as first degree atrioventricular block are commonly present and rarely merit further work up. Occasionally, patients develop advanced conduction defects which can unexpectedly progress to complete heart block perioperatively

La distrofia miotonica clásica es un trastorno multi-sistémico que resulta de la toxicidad del RNA y es una de las distrofias musculares más comunes en adultos. Los pacientes suelen presentar rigidez muscular por la miotonía, así como disfagia o disartria por debilidad muscular laringo-faríngea-esofágica. Los cambios benignos en el electrocardiograma, como el bloqueo auriculoventricular de primer grado, suelen estar presentes y rara vez merecen un análisis más profundo. Ocasionalmente, los pacientes desarrollan defectos de conduccion avanzados que pueden progresar inespera-damente para completar el bloqueo cardiaco perioperatorio.

Ações Transmurais Inotrópicas e Antiarrítmicas da Ranolazina em um Modelo Celular da Síndrome do QT Longo Tipo 3 / Inotropic and Antiarrhythmic Transmural Actions of Ranolazine in a Cellular Model of Type 3 Long QT Syndrome

Resumo A Ranolazina (RANO), conhecida na clínica como Ranexa, é um fármaco que previne a arritmia cardíaca através da inibição da corrente de sódio tardia (INaT). Um gradiente de voltagem transmural do canal Nav1.5 encontra-se na parede ventricular esquerda do coração. Assim, investigamos os efeitos da RANO em cardiomiócitos saudáveis e em modelo celular da Síndrome do QT longo tipo 3 (SQTL tipo 3). Usamos células isoladas do endocárdio (ENDO) e do epicárdio (EPI) e um software de medição com detecção de bordas por vídeo e microscopia de fluorescência para monitorar os transientes de cálcio. A RANO (0,1, 1, 10 e 30 uM, a 25OC) em uma série de frequências de estimulação teve impacto pouco significativo sobre ambos os tipos de células, mas a RANO (30uM) a 35OC minimizou o encurtamento dos sarcômeros em ~21% para células do endocárdio. Em seguida, para simular a SQTL tipo 3, as células do ENDO e EPI foram expostas à toxina ATX-II da anêmona do mar, que aumenta a INaT. As arritmias celulares induzidas por ATX-II foram suprimidas com o uso da RANO (30 µM) a 35OC. Com base nesses resultados, podemos concluir que a RANO tem um impacto pouco significativo sobre o encurtamento dos sarcômeros de células saudáveis do ENDO e EPI. Além disso, ela suprime as arritmias induzidas por INaT para níveis semelhantes nas células do ENDO e EPI.

Abstract Ranolazine (RANO) prevents cardiac arrhythmia by blocking the late sodium current (INaL). A transmural gradient of Nav1.5 is found in the left ventricular wall of the heart. Thus, we investigated the effects of RANO in healthy cardiomyocytes and in a cellular model of type 3 long QT syndrome (LQT3). We used isolated endocardium (ENDO) and epicardium (EPI) cells and a video edge detection system and fluorescence microscopy to monitor calcium transients. RANO (0.1, 1, 10 and 30 uM, at 25oC) at a range of pacing frequencies showed a minor impact on both cell types, but RANO at 30uM and 35oC for ENDO cells attenuated sarcomere shortening by~21%. Next, to mimic LQT3, we exposed ENDO and EPI cells to anemone toxin II (ATX-II), which augments INaL. Cellular arrhythmias induced by ATX-II were abrogated by RANO (30 µM) at 35oC. Based on our results we can conclude that RANO has a minor impact on sarcomere shortening of healthy ENDO and EPI cells and it abrogates arrhythmias induced by INaLto a similar level in ENDO and EPI cells.

Asociación de la dilatación auricular izquierda con los trastornos del sistema de conducción en pacientes con hipertensión arterial sistémica / Association of left atrial dilatation with conduction system disorders in patients with systemic arterial hypertension

La dilatación de la aurícula izquierda (AI) se considera un predictor ecocardiográfico para la remodelación auricular y la fibrilación auricular. Por ende, hemos investigado la correlación existente entre la dilatación de la AI con las arritmias cardíacas y los trastornos del sistema de conducción en pacientes con hipertensión arterial (HTA). En este estudio observacional y prospectivo hemos investigado las variaciones electrocardiográficas, mediciones ecocardiográficas y Holter ECG de 24 hs en pacientes hipertensos y no hipertensos ambulatoria y hospitalizados que acuden a un hospital terciario entre marzo a septiembre del 2018. Se estudiaron 104 pacientes, 65 hipertensos conocidos y 39 no hipertensos como grupo control. El diámetro promedio de la AI fue significativamente mayor (p=0,03) en pacientes hipertensos que los no hipertensos (37±8 mm vs. 34±5 mm). Se encontró una asociación significativa entre hipertensión y la aurícula izquierda dilatada (>40 mm) (p= 0,026 OR: 3,25 IC95%: 1,01-11,02). La dilatación de la AI tuvo una especificidad de 73% y un valor predictivo negativo de 98% relacionado con la presencia de trastornos del sistema de conducción y arritmias cardiacas en pacientes con HTA. Se encontró asociación entre la hipertensión arterial y la dilatación de la aurícula izquierda. La dilatación de la aurícula izquierda tiene una elevada especificidad y un alto valor predictivo negativo en la detección de la presencia de prolongación del intervalo QT, ensanchamiento del complejo QRS, dispersión de la onda P, y trastornos del sistema de conducción y arritmias cardiacas en pacientes con hipertensión arterial(AU)

Dilation of the left atrium (LA) is considered an echocardiographic predictor for atrial remodeling and atrial fibrillation. Therefore, we have investigated the correlation between dilatation of the LA with cardiac arrhythmias and conduction system disorders in patients with systemic arterial hypertension. In this observational and prospective study we have investigated electrocardiographic variations, echocardiographic measurements and Holter ECG of 24 hours in hypertensive patients who attend a tertiary hospital from March 2018 to September 2018 as outpatients and inpatients. One hundred four patients were studied, 65 known to be hypertensive and 39 non-hypertensive subjects as control group. The diameter of the LA ​​had a mean value of 37±8 in hypertensive patients, while in non-hypertensive patients was 34±5 ​​(p = 0.03). A significant association was found between hypertension and increased diameter of the LA (p = 0.04 OR: 2.6 CI 0.88-7.7). Dilatation of the LA had a specificity of 73% and a negative predictive value of 98% related to the presence of conduction system disorders and cardiac arrhythmias in patients with hypertension. A significant relationship between arterial hypertension and dilatation of the left atrium was observed. The dilatation of the left atrium has a high specificity and a high negative predictive value in the detection of the presence of prolongation of the QT interval, widening of the QRS complex, dispersion of the P wave, and disorders of the conduction system and cardiac arrhythmias in patients with hypertension(AU)

Assessment of Subclinical Cardiac Alterations and Atrial Electromechanical Delay by Tissue Doppler Echocardiography in Patients with Nonfunctioning Adrenal Incidentaloma / Avaliação de Alterações Cardíacas Subclínicas e Atraso Eletromecânico Atrial por Ecocardiografia com Doppler Tecidual em Pacientes com Incidentaloma Adrenal Não Funcionante

Abstract Background: Majority of the incidentally discovered adrenal masses, called adrenal incidentaloma (AI), are nonfunctioning adrenal adenomas. The appropriate management of AI is still a matter debate, so it is necessary to investigate their associated morbidity. However, data regarding morphological and functional cardiac alterations are limited in this group. Objective: In this study, we aimed to assess cardiac structural and functional characteristics and atrial conduction properties in patients with nonfunctioning AI. Methods: Thirty patients with nonfunctioning AI and 46 properly matched control subjects were included in the study. After hormonal and biochemical analysis, all participants underwent transthoracic echocardiography to obtain systolic and diastolic parameters of both ventricles, in addition to atrial conduction times by tissue Doppler echocardiography. Data were analyzed with Statistical Package for the Social Sciences (SPSS, Chicago, IL, United States) statistics, version 17.0 for Windows. P < 0.05 was considered statistically significant. Results: Left ventricular (LV) mass index and LV myocardial performance index were significantly increased in AI group. Among atrial conduction times, both intra- and interatrial electromechanical delays were significantly prolonged in patients with nonfunctioning AI. Other laboratory and echocardiographic findings were similar between groups. Conclusion: Our study revealed that intra- and inter-atrial conduction times were prolonged, and LV mass index was increased in patients with nonfunctioning AI. These findings may be markers of subclinical cardiac involvement and tendency to cardiovascular complications. Close follow-up is necessary for individuals with nonfunctioning AI for their increased cardiovascular risk.

Resumo Fundamento: A maioria das massas adrenais descobertas incidentalmente, denominadas incidentaloma adrenal (IA), são adenomas adrenais não funcionantes. O manejo adequado da IA ainda é um tema de debate, e por isso é necessário investigar suas morbidades associadas. Entretanto, dados referentes a alterações cardíacas morfológicas e funcionais são limitados nesse grupo. Objetivo: Neste estudo, objetivamos avaliar as características estruturais e funcionais cardíacas e as propriedades de condução atrial em pacientes com IA não funcionante. Métodos: Trinta pacientes com IA não funcionante e 46 controles adequadamente pareados foram incluídos no estudo. Após análise hormonal e bioquímica, todos os participantes foram submetidos a ecocardiograma transtorácico para obtenção de parâmetros sistólicos e diastólicos de ambos os ventrículos, além dos tempos de condução atrial pelo ecocardiograma com Doppler tecidual. Os dados foram analisados com o Statistical Package for the Social Sciences (SPSS, Chicago, IL, Estados Unidos), versão 17.0 para Windows. P < 0,05 foi considerado estatisticamente significativo. Resultados: O índice de massa do ventrículo esquerdo (VE) e o índice de desempenho miocárdico do VE foram significativamente aumentados no grupo IA. Entre os tempos de condução atrial, os atrasos eletromecânicos intra- e interatriais foram significativamente prolongados em pacientes com IA não funcionante. Outros achados laboratoriais e ecocardiográficos foram semelhantes entre os grupos. Conclusão: Nosso estudo revelou que os tempos de condução intra- e interatrial estavam prolongados e o índice de massa do VE estava aumentado em pacientes com IA não funcionante. Esses achados podem ser marcadores de envolvimento cardíaco subclínico e de tendência a complicações cardiovasculares. Um acompanhamento rigoroso é necessário para indivíduos com IA não funcionante, devido ao aumento do risco cardiovascular.

Distúrbios de condução cardíaca e taquicardia ventricular como complicação da granulomatose com poliangiíte em uma paciente. Relato de caso e revisão da literatura / Heart conduction system defects and sustained ventricular tachycardia complications in a patient with granulomatosis with polyangiitis. A case report and literature review

RESUMO A granulomatose com poliangiíte é um raro distúrbio inflamatório sistêmico que se caracteriza por vasculite de pequenas artérias, arteríolas e capilares, associada a lesões granulomatosas necrotizantes. Este artigo relata o caso de uma paciente com diagnóstico prévio de granulomatose com poliangiíte, admitida à unidade de terapia intensiva com quadro de crises convulsivas e instabilidade hemodinâmica em razão de bloqueio atrioventricular completo. Estas manifestações se associaram a múltiplos episódios de taquicardia ventricular sustentada; não havia alterações estruturais cardíacas, nem se detectaram distúrbios hidroeletrolíticos. Na unidade de terapia intensiva, a paciente foi submetida à implantação de marca-passo provisório, imunossupressão com uso de corticosteroides e terapia imunobiológica, resultando em melhora hemodinâmica completa. Distúrbios graves da condução cardíaca em pacientes com granulomatose com poliangiíte são raros, mas associam-se à grande morbidade. O reconhecimento precoce e o uso de intervenções específicas são capazes de prevenir a ocorrência de desfechos desfavoráveis, especialmente na unidade de terapia intensiva.

ABSTRACT Granulomatosis with polyangiitis is a rare systemic inflammatory disorder characterized by vasculitis of the small arteries, the arterioles and the capillaries together with necrotizing granulomatous lesions. This case reports on a young female patient, previously diagnosed with granulomatosis with polyangiitis, who was admitted to the intensive care unit with seizures and hemodynamic instability due to a complete atrioventricular heart block. The event was associated with multiple episodes of sustained ventricular tachycardia without any structural heart changes or electrolyte disturbances. In the intensive care unit, the patient was fitted with a provisory pacemaker, followed by immunosuppression with corticosteroids and immunobiological therapy, resulting in a total hemodynamic improvement. Severe conduction disorders in patients presenting granulomatosis with polyangiitis are rare but can contribute to increased morbidity. Early detection and specific intervention can prevent unfavorable outcomes, specifically in the intensive care unit.

Changes in P-wave, T-wave, and ST segment amplitude in 12 lead electrocardiogram in children with breath holding spell / 中南大学学报(医学版)

OBJECTIVE@#To explore the change of the amplitude of P wave, T wave and ST segment of 12 lead electrocardiogram (ECG) in children with breath holding spell.
@*METHODS@#A total of 29 children (24 males and 5 females) with breath holding spell in Second Xiangya Hospital, Central South University were enrolled for this study from October, 2009 to September, 2015. Their ages ranged from 3 months to 6 years, with an average of 1.82±1.27 years old. The control group consisted of 30 age-matched and gender-matched healthy children. All subjects were underwent electrocardiography by the SR-1000A comprehensive automatic electrocardiograph analyzer, and the changes of the ECG parameters were compared between the two groups.
@*RESULTS@#Compared with the control group, the amplitude of P-wave of V5 lead was decreased [(44.10±23.98) vs (58.30±21.19) μV, P<0.05], the amplitude of T-wave of V6 lead was increased [(423.80±122.6) vs (350.00±105.73) μV, P<0.05], the amplitude of ST segment of II lead was increased [(84.80±39.97) vs (57.30±38.77) μV, P<0.05], the amplitude of ST segment of aVR lead was increased [(-77.60±37.41) vs (-51.00±33.46) μV, P<0.05], the amplitude of ST segment of aVL lead was increased [(35.20±28.24) vs (17.70±33.90) μV, P<0.05], the amplitude of ST segment of V5 lead was increased [(111.00±59.36) vs (69.00±36.33) μV, P<0.05], the amplitude of ST segment of V6 lead was increased [(79.30±45.51) vs (51.30±33.19) μV, P<0.05]. 
@*CONCLUSION@#The children with breath holding spell have autonomic nerve dysfunction. The amplitude of ST segment changes is sensitive.

Relationship between electrocardiographic and genetic mutation (MYH7-H1717Q, MYLK2-K324E and KCNQ1-R190W) phenotype in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relationship between electrocardiographic (ECG) and genetic mutations of patients with hypertrophic cardiomyopathy (HCM), and early ECG changes in HCM patients.</p><p><b>METHODS</b>Clinical, 12-lead ECG and echocardiographic examination as well as genetic examinations were made in a three-generation Chinses HCM pedigree with 8 family members (4 males). The clinical characterization and ECG parameters were analyzed and their relationship with genotypes in the family was explored.</p><p><b>RESULTS</b>Four missense mutations (MYH7-H1717Q, MYLK2-K324E, KCNQ1-R190W, TMEM70-I147T) were detected in this pedigree. The proband carried all 4 mutations and 5 members carried 2 mutations. Corrected QTc interval of KCNQ1-H1717Q carriers was significantly prolonged and was consistent with the ECG characterization of long QT syndrome. MYLK2-K324E and KCNQ1-R190W carriers presented with Q wave and(or) depressed ST segment, as well as flatted or reversed T waves in leads from anterolateral and inferior ventricular walls. ECG results showed ST segment depression, flat and inverted T wave in the gene mutation carriers with normal echocardiographic examination results. ECG and echocardiographic results were normal in TMEM70-I147T mutation carrier.</p><p><b>CONCLUSIONS</b>The combined mutations of the genes associated with cardiac ion channels and HCM are linked with the ECG phenotype changes in this HCM pedigree. The variations in ECG parameters due to the genetic mutation appear earlier than the echocardiography and clinical manifestations. Variation in ECG may become one of the indexes for early diagnostic screening and disease progression of the HCM gene mutation carriers.</p>

High incidence of sudden cardiac death in one family with type-3 long QT syndrome: molecular genetics and electrophysiology mechanism analysis / 中华心血管病杂志

<p><b>OBJECTIVES</b>We identified the long QT syndrome (LQTS) patients, and detected the potential risk of LQTS in family members by using genetic testing and electrophysiological analysis, which helped provide clinical evaluation and appropriate treatment.</p><p><b>METHODS</b>Detailed clinical characteristics and familiar history were obtained from the whole family members of an idiopathic pediatric LQTS patient. Two hundred healthy subjects with the same ethnic background were recruited as controls. The entire coding sequences of three candidate genes including KCNQ1, KCNH2 and SCN5A were screened for mutations in the proband. The function of the mutation was then explored by whole-cell patch clamp techniques, and the genetic testing and risk assessment of the family members were performed.</p><p><b>RESULTS</b>The proband was clinically preliminary diagnosed as LQTS by 12-lead electrocardiogram. On the third day of metoprolol intake (25 mg, bid), she died suddenly at lunch. One heterozygous missense mutation (SCN5A-V411M) was identified in this proband, but the mutation was absent in 200 healthy subjects. The electrophysiological analysis indicated that SCN5A-V411M significantly increased the peak current density ((230.8 ± 27.6)pA/pF vs. (101.2 ± 10.9)pA/pF, n=10, P<0.01) and the late sodium current ((156.6 ± 13.6)pA/pF vs. (95.9 ± 7.9)pA/pF, n=12, P<0.01) of sodium channel compared to wide type. The enhanced sodium channel activation with a negative shift in the peak I-V relationship was significantly higher by -50 mV than wide type (85.0%± 7.4% vs. 41.5% ± 2.6%, P<0.01), while the steady-state inactivation curves remained unchanged. Additionally, mother and grandmother of the proband were the silent mutation carriers with no symptoms, who needed the appropriate clinical assessment and follow-up. The proband's twin sister and aunt died of sudden infant death syndrome.</p><p><b>CONCLUSIONS</b>We firstly reported a heterozygote missense mutation (SCN5A-V411M) in this Chinese family. V411M induced "gain of function" of sodium channel and formed the basis of type-3 LQTS. Genetic testing could help to increase the diagnostic accuracy, and facilitate clinical assessment and appropriate therapy to prevent sudden cardiac death of individuals with SCN5A-V411M mutation.</p>

Long-term outcome after cardioverter-defibrillator implantation in patients with Brugada syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the long-term outcome of implantable cardioverter-defibrillator (ICD) implantation in Brugada syndrome patients and to explore how to reduce the frequency of ICD nappropriate schocks.</p><p><b>METHODS</b>This study included 14 symptomatic patients (mean age (44.3 ± 8.3) years old; all males) with Brugada syndrome implanted with ICD in our hospital between 1998 and 2012, and these patients were followed up routinely every 6 months. The initial ICD parameters were set according o conventional experience. The ventricular tachycardia (VT) zone was programmed to ventricular rate 150-188 bpm/cycle length (CL) 400-320 ms and the ventricular fibrillation (VF) zone was programmed to ventricular rate ≥ 188 bpm/CL ≤ 320 ms. The total events were recorded by ICD. The ICD parameters revision was made by electrophysiological (EP) experts in case of inappropriate shocks.</p><p><b>RESULTS</b>Patients were followed up for mean (43.0 ± 28.3) months. A total of 297 VF/VT events were recorded by ICD. Electrophysiological experts found that 90% (178/198) episodes were true VF ( CL 130-250 ms) among of 198 VF episodes and 147 VF episodes were terminated by one shock and 21 VF events were terminated by two or more shocks, and the rest 10 VF terminated spontaneously. Only 9% (9/99) VT events were true VT (CL 320-360 ms) among of 99 VT episodes. Eight VT episodes were converted by antitachycardia pacing therapy (ATP) and the other one terminated spontaneously. The rest 90 VT episodes (91%) were supraventricular arrhythmias (SVT, CL 340-390 ms). About 90% inappropriate shocks can be reduced by Wavelet discrimination function and optimal programming (VF zone ventricular rate ≥ 222 bpm/CL ≤ 270 ms and/or VT zone ventricular rate 167-222 bpm/CL 270-360 ms ) according to the characteristics of arrhythmia of individual patient.</p><p><b>CONCLUSION</b>ICD can effectively prevent sudden cardiac death and syncope in high-risk patients with Brugada syndrome. The most common complication is inappropriate shock due to SVT. Optimal ICD programming with Wavelet discrimination function can effectively reduce the frequency of inappropriate shock rate.</p>

Continuous positive airway pressure treatment for functional cardiac arrhythmias combined with obstructive sleep apnea hypopnea syndrome / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To discuss the effect of continuous positive airway pressure (CPAP) treatment for functional cardiac arrhythmias combined with obstructive sleep apnea hypopnea syndrome.</p><p><b>METHODS</b>Fifty-six OSAHS patients combined functional cardiac arrhythmia were randomized divided into two groups. The 28 patients in the control group were treated with metoprolol according to cardiac guidelines, the other 28 cases in the experimental group were treated with CPAP therapy combined with metoprolol. AHI and the lowest oxygen saturation (LSaO2) were tested before and after treatment.</p><p><b>RESULTS</b>The efficiency rates were 57.1% and 17.9% in experimental and control group respectively, with statistical difference (χ2 = 7.62, P < 0.01). Total effective rates were 85.7% and 53.6% respectively, with statistical difference (χ2 = 5.41, P < 0.05). In the experimental group, there were three treatment subgroups. After treatment, AHI and the lowest oxygen saturation were significantly different (P < 0.05).</p><p><b>CONCLUSION</b>CPAP treatment can effectively eliminate respiratory disturbance index, improve the symptoms of hypooxygen at night, and effectively improve the therapeutic effect of functional cardiac arrhythmias in OSAHS patients combined with functional arrhythmia.</p>

2-Methylthio-adenosine-5'-triphosphate inhibits ventricular arrhythmogenesis in rabbits with chronic heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects and related mechanisms of 2-methylthio-adenosine-5'-triphosphate (2-MeSATP), an important extracellular agonist that activates receptors for purine nucleotides (P2XR), on ventricular arrhythmias in rabbits with chronic heart failure (CHF).</p><p><b>METHODS</b>The male New Zealand rabbits were divide into control (n=12), CHF (n=12) and CHF+2-MeSATP groups (2-MeSATP, n=12). CHF was induced by isoproterenol injection (0.3 mg·kg⁻¹·d⁻¹ for 3 weeks) and rabbits were observed 6 months later. The main cardioelectrophysiological parameters and ventricular arrhythmias were tested by recording monophasic action potential (MAP) with burst-pacing (BCL) in rabbits in vivo. The transient outward potassium current (Ito) was recorded via whole-cell patch clamp technique and the fluorescence intensity of intracellular free Ca²⁺ was detected with Flup-3/AM loading by the laser scanning confocal microscope in enzymatically dissociated single rabbet ventricular myocytes.</p><p><b>RESULTS</b>CHF rabbits developed severely clinical CHF signs and symptoms, reduced left ventricular ejection fraction and fractional shortening as well as enlarged end-diastolic dimension. Compared with CHF group, APA and MaxdV/dt were significantly increased, while APD20, APD50 and APD90 were significantly reduced in 2-MeSATP group (all P<0.01). Moreover, 2-MeSATP could obviously shorten BCL induced ventricular arrhythmias, and decrease deducibility and persistence time of ventricular arrhythmias with burst-pacing in 2-MeSATP group in vivo (all P<0.05). With voltage clamp model, 2-MeSATP could significantly increase the current density of Ito in different command potential in CHF ventricular myocytes (all P<0.01). When holding potential was set at -50 mV and command potential was set at +50 mV, the current densities of Ito increase was more significant in 2-MeSATP group than that in CHF group ((11.79 ± 4.51) pA/pF vs. (7.94 ± 3.53) pA/pF, P<0.01). 2-MeSATP could completely change the I-V curve upward without changing the I-V curve direction in CHF ventricular myocytes. The fluorescence intensities of intracellular free Ca²⁺ increase was more significant in 2-MeSATP group compared to CHF group ((1 291.98 ± 123.31) µmol/L vs. (793.59 ± 114.65) µmol/L, P<0.01).</p><p><b>CONCLUSION</b>2-MeSATP as a potent agonist acting on P2XR could significantly shorten APD, increase heart rate and improve cardiac performance as well as decrease the susceptibility of ventricular arrhythmias in this rabbit CHF model. Our results suggest that Ito increase and sarcoplasmic reticulum uptake Ca²⁺ enhancement as well as dynamic balance of intracellular Ca²⁺ cycling sustenance might linked to the beneficial effects of 2-MeSATP in this CHF model.</p>

Combined transgenic inhibition of CaMKII and Ik1 on cardiac remodeling / 生理学报

This study was aimed to establish an experimental mouse model of combined transgenic inhibition of both multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and inward rectifier potassium current (Ik1), and to observe whether the specific inhibition of both CaMKII and Ik1 can bring about any effects on cardiac remodeling. Mice were divided into 4 groups: wild type (WT), CaMKII inhibited (AC3-I), Ik1 inhibited (Kir2.1-AAA) and combined inhibition of both CaMKII and Ik1 (AC3-I+Kir2.1-AAA). Mice in each group received electrocardiogram (ECG) and echocardiography examination. ECG in the condition of isoproterenol (ISO) injection was also checked. The whole cell patch clamp technique was used to measure Ik1 and the transient outward potassium current (Ito) from enzymatically isolated myocytes of left ventricle. In the condition of basal status, no significant changes of heart rate, PR interval and QRS interval were observed. No mouse showed ventricular arrhythmias in all of the 4 groups. After ISO injection, each group presented no significant ventricular arrhythmias either. The indexes measured by M-mode (motion-mode) and two-dimensional echocardiography had no significant differences among the four groups. Ik1 in AC3-I group was significantly higher than those in other three groups (P < 0.01) because of the results brought about by CaMKII inhibition. Among the latter three groups, both Kir2.1-AAA group and AC3-I+Kir2.1-AAA group had a significant reduced Ik1 compared with that of WT group, which was due to the Ik1 inhibition (P < 0.01). Ito in AC3-I group was higher than that of the other three groups (P < 0.01), but there were no significant differences in Ito among WT, Kir2.1-AAA and AC3-I+Kir2.1-AAA groups. Thus, combined transgenic myocardial CaMKII and Ik1 inhibition eliminated the up-regulation of Ik1 in CaMKII inhibited mice, and had no effects on cardiac remodeling including heart structure and function as well as arrhythmias at the basic and ISO conditions. The results of this study may provide a basis for the further investigation of combined inhibition of CaMKII and Ik1 in pathogenic cardiac remodeling.

Clinical characteristics and prognosis comparison of Chinese non ST-segment elevation acute coronary syndrome patients in two different time periods / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the clinical characteristics, treatment methods and outcomes in Chinese non ST-segment elevation acute coronary syndrome (NSTE-ACS) patients from two large clinical trials in different time periods.</p><p><b>METHODS</b>All Chinese NSTE-ACS patients from two large International clinical trials (OASIS Registry and TIMACS) underwent coronary artery angiography after first admission were recruited in our analysis. The follow-up time was 180 days. A total of 1 473 NSTE-ACS patients were recruited in this analysis, in which 749 from Organization to Assess Strategies for Ischemic Syndromes (OASIS REISTRY) that completed in 38 centers in China from April 1999 to December 2000, and the rest 724 patients from The Timing of Intervention in Acute Coronary Syndromes (TIMACS) trial in 24 centers in China performed from April 2007 to June 2008.</p><p><b>RESULTS</b>Compared to OASIS patients, TIMACS group were older ((64.2 ± 10.1) years old vs. (58.7 ± 10.2) years old) , and fewer male patients (66.3% (480/724) vs. 74.4% (557/749)) , lower blood pressure at admission, and more histories of previous PCI (9.4% (68/724 vs. 6.4% (48/749)), stroke (8.8% (64/724) vs. 5.1% (38/749)) , hypertension (62.8% (455/724) vs. 56.6% (424/749)) and diabetes (23.3% (169/724) vs. 16.2% (121/749)), lower histories of coronary artery disease (37.4% (271/724) vs. 59.1% (443/749)) and myocardial infarction (12.0% (87/724) vs. 27.6% (207/749)) (all P < 0.05). After admission, comparing to OASIS group, TIMACS patients had significant higher PCI proportion (74.9% (524/724) vs. 49.3% (369/749), P < 0.001). In addition, for secondary prevention, TIMACS patients had significant higher standard medication treatment proportion during hospitalization, at discharge and at 180 days follow up than OASIS group (P < 0.05 for β-blocker, ACEI/ARB and lipid lowering drugs) and higher compliance rate. The combined primary outcome event rate at 180 days was much lower in TIMACS than in OASIS patients (13.3% (96/724) vs. 25.2% (189/749), P < 0.001) mostly due to the reduction on the refractory angina (5.2% (38/724) vs. 22.6% (169/749), P < 0.001) .</p><p><b>RESULTS</b>of COX regression model adjusted for baseline levels and treatment during hospitalization showed that the incidence rate of combination endpoint (HR = 0.39, 95% CI: 0.29-0.53, P < 0.001) and refractory ischemia/angina rehospitalization (HR = 0.17, 95% CI: 0.11-0.25, P < 0.001) were both lower in TIMACS patients than in OASIS patients.</p><p><b>CONCLUSION</b>PCI procedure and secondary prevention medication administration are more often applied in TIMACS patients than in OASIS group, which is related to less integrated incidence of primary outcomes reflecting progress in Chinese medical care for non ST elevated acute coronary syndrome patients according to the updated guidelines.</p>

κ-opioid receptor agonist U50, 488H attenuates myocardial ischemia-reperfusionvia modulating Toll-like receptor 4/nuclear factor-κB signaling in rat / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effects of κ-opioid receptor agonist U50, 488H on myocardial ischemia and reperfusion injury and related mechanism.</p><p><b>METHODS</b>Rats were randomly divided into sham operation, myocardial ischemia and reperfusion(I/R, 30 min ischemia followed by 120 min reperfusion), and MI/R+U50, 488H (1.5 mg/kg) and I/R+U50, 488H+ selective κ-opioid receptor antagonist Nor-BNI (2 mg/kg, n = 8 each). The infarction size and the incidence of ventricular arrhythmias were observed.Real-time PCR and DAB staining were used to define the myocardium Toll-like receptor 4(TLR4) expression. Myeloperoxidase level, TNF-α induction and the expression of NF-κB were also examined in rats.</p><p><b>RESULTS</b>After I/R, the expressions of myocardial TLR4 and NF-κB increased significantly both in ischemia area and area at risk. Compared with I/R, κ-opioid receptor stimulation with U50, 488H significantly attenuated the expressions of TLR4 and NF-κB and reduced myeloperoxidase (MPO) levels, myocardial TNF-α production, myocardial infarct sizes and the incidence of ventricular arrhythmias and arrhythmia score (2.9 ± 0.7 vs. 4.4 ± 0.9, P < 0.05) , above effects of U50, 488H were partly abolished by co-treatment with Nor-BNI.</p><p><b>CONCLUSION</b>These data provide evidence for the first time that κ-opioid receptor stimulation could attenuate myocardial I/R injury via downregulating TLR4/NF-κB signaling in rats.</p>

Research progress of Tbx3 in cardiac biological pacemaker / 生物医学工程学杂志

The early cardiac biological pacemaker studies were mostly around HCN channel, and how to build a biological pacemaker through the enhanced If current. In recent years, however, people found that the genes of Tbx3 could play an important role in the development of cardiac conduction system, especially in processes of the maturity of the sinoatrial node and maintenance of its function. And the Tbx3 can further optimize the biological pacemaker. Therefore, it could be a new therapeutic focus in biological pacemaker and treatment of cardiac conduction system disease. This paper summarizes some of the latest research progress of the Tbx3 in biological pacemaker in recent years. We hope that this review could provide theoretical basis for the clinical applications of Tbx3.

Progress in endogenous cardioprotection induced by ischemic postconditioning / 生理学报

Restoration of blood flow is the definitive therapy to salvage myocardium following ischemic injury. Sudden restoration of blood flow to the ischemic myocardium may, however, also cause reperfusion injury. Therefore, to prevent such ischemia/reperfusion (I/R) injury, one strategy could be to evoke endogenous myocardial protective mechanisms. Ischemic preconditioning (IPC) and postconditioning (I-postC) are endogenous protective mechanisms capable of protecting the myocardium from myocardial infarction, stunning, and ventricular arrhythmia induced by I/R injury. The mechanisms involve induction of triggers, activation of signaling pathways, and end-effectors, which attenuate generation of free radicals and calcium overload induced by I/R. The fact that I-postC can be applied after a prolonged period of ischemia offers a novel approach to myocardial protection. This article mainly reviews the cardioprotection, mechanisms, and application to clinical cardiology of I-postC.

Taquicardia ventricular idiopática de dos morfologías asociada a trastorno de conducción aurículo-ventricular / Idiopathic ventricular tachycardia of two morphologies associated with atrioventricular conduction disorder

Introducción: Las taquicardias ventriculares idiopáticas son arritmias poco frecuentes. Se pueden originar tanto en el ventrículo derecho como el izquierdo. Caso Clínico: En un paciente de 56 años sintomático por palpitaciones se constata en electrocardiograma basal taquicardia ventricular monomorfa repetitiva y bloqueo AV de primer grado. Resultados: El estudio electrofisiológico logro inducir una taquicardia monomorfa y sostenida. El tratamiento con betabloqueantes fue inefectivo y se inicio tratamiento con amiodarona. Se repitió estudio electrofisiológico con tratamiento para evaluar respuesta. El paciente permaneció asintomático en 14 meses de seguimiento. Conclusiones: Los b-bloqueantes son una buena alternativa para las taquicardias ventriculares idiopáticas pero en este caso no fue efectivo. El tratamiento con amiodarona seria una opción efectiva y segura a considerar es estos casos.

Introduction: Idiopathic ventricular tachycardias are rare arrhythmias. They can originate both in the right or left ventricle. Clinical Case: The basal electrocardiogram (ECG) recording of a 56 year old patient with palpitations shows repetitive monomorphic ventricular tachycardia (RMVT) and first-degree AV block. The electrophysiological study could induce monomorphic and sustained tachycardia. Treatment with b-blockers proved ineffective, thus, amiodarone treatment was prescribed. Results: The electrophysiological study was repeated with treatment in order to assess the patient's response. The patient did not present any symptoms in 14 months of follow-up. Conclusions: b-blockers are a good alternative for idiopathic ventricular tachycardias; however, in this particular case they were ineffective. Amiodarone treatment would be an effective and safe choice to be considered in these cases.