The Role of Beta-Blockers as First-Line Therapy in Hypertension

National and international guidelines still recommend β-blockers (BBs) as first-line agents in uncomplicated prevention of hypertension. However, it has been shown that BBs reduce blood pressure less than other drugs, specifically with regard to central aortic pressure. More importantly, recent meta-analyses have highlighted that in primary prevention BBs are associated with a relatively weak effect in reducing stroke compared to placebo or no treatment and, compared with other drugs, show evidence of a worse cardiovascular outcome. Several reasons might explain their mild cardioprotective effect, such as their unfavorable metabolic properties, a lack of efficacy on left ventricular hypertrophy regression and endothelial dysfunction, and reduced patient compliance. Thus, the available evidence does not support the use of BBs as first-line drugs in the treatment of uncomplicated hypertension. It remains to be determined whether newer BBs, such as nebivolol and carvedilol, will be more effective than older compounds in improving cardiovascular prognosis.     

蒽环类药物抗肿瘤治疗与室性心律失常

蒽环类药物（Anthracyclines,ANT）是一种抗细胞有丝分裂的药物,因具有良好的抗肿瘤作用而成为乳腺癌、淋巴瘤、白血病等恶性肿瘤的基础用药,但它的使用受到剂量依赖性心脏毒性的限制,能够引起心律失常、心力衰竭、心肌损伤等心脏并发症。癌症患者因使用ANT可能导致心电活动紊乱,进而可能发生室速、室颤甚至猝死,但目前临床上对于ANT引起的室性心律失常暂无特效的预防和治疗方法。而ANT引起室性心律失常的机制可能涉及自主神经失平衡、氧化应激、线粒体损伤、铁代谢紊乱和电活动相关离子平衡紊乱等方面。本文将介绍ANT引起室性心律失常的基础研究和临床研究进展,总结临床上的常用预防和治疗方案,并结合自主神经再平衡策略,为减轻ANT致室性心律失常提供新的干预思路。     

希氏-浦肯野系统和室性心律失常

近期研究提示希氏-浦肯野系统与室性心律失常的发生关系密切。作为左室的特殊传导组织,希氏-浦肯野系统的解剖与电生理特点,使其在正常或病理情况下易于参与折返型心律失常形成。目前资料提示浦肯野系统病变是短联律间期室性早搏相关心律失常和儿茶酚胺敏感性多形性室性心动过速的原因。随着对希氏-浦肯野系统与室性心律失常关系的认识,导管消融可作为此类心律失常的治疗途径。     

Antiarrhythmic Drug Therapy for Ventricular Arrhythmias: Current Perspectives

Antiarrhythmic Drug Therapy. Pharmacologic therapy for ventricular arrhythmias has undergone a remarkable change recently. Recognition of the importance of underlying structural heart disease on prognostic implications of ventricular arrhythmias has resulted in the refinement of the clinical classification of these arrhythmias. With refinement of techniques of risk stratification, it is now possible to identify patients with ventricular arrhythmias at high risk for sudden death. Retrospective analyses of prior antiarrhythmic drug trials and new data from prospective randomized trials are now available and can more directly define the risks and benefits of antiarrhythmic therapy. Prevention of sudden death, reduction in total mortality, or improvement in symptoms remain the only benefits of antiarrhythmic drugs. With inclusion of total mortality as the major endpoint for assessment of pharmacologic interventions in high-risk patients, the potential for excess mortality due to antiarrhythmic agents is now recognized. The pharmacologic diversity of newly released antiarrhythmic agents and others under development has resulted in a re-evaluation of the traditional classification of these drugs. Multiple ongoing clinical trials will define the risks and benefits of antiarrhythmic therapy and other nonpharmacologic interventions in patients with ventricular arrhythmias.     

New Information on the Role of Beta-Blockers in Cardiac Therapy

Summary. Hypertension and ischemic heart disease are important precursors of heart failure. The prevention of progression to heart failure is a prime objective when treating patients with hypertension or ischemic heart disease. In patients with hypertension, treatment with either diuretics or beta-blockers reduces the risk of chronic heart failure. In patients with ischemic heart disease, beta-blocker therapy reduces the risk of recurrent myocardial infarction and ensuing cardiac dysfunction. The beneficial effects of beta-blocker therapy may be greater in post-infarction patients who have impaired left ventricular function than in those patients without such impairment.When considering heart failure itself, the efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in patients with mild-to-severe left ventricular dysfunction and their use is indicated for all stages of heart failure to reduce symptoms and retard further impairment of left ventricular function. Diuretics and digitalis offer relief from the symptoms of the disease, while positive inotropes are reserved for parenteral administration in end-stage heart failure, as a bridge to transplantation, or in acute exacerbations of the disease. Added to standard therapy, beta-blockade is of value in the treatment of heart failure, preventing further deterioration and improving hemodynamics, exercise tolerance, quality of life, and long-term prognosis.     

Mexiletine: Its Role in the Management of Chronic Ventricular Arrhythmias

Mexiletine is a class IB anti arrhythmic agent structurally similar to lidocaine but with the advantage of a high bioavailability and relatively long half-life, making it useful for long-term oral therapy of ventricular arrhythmias. Mexiletine can be used orally or intravenously. Orally, it has a high bioavailability, reaching peak plasma concentration between 2 and 4 hours after administration. The steady-state therapeutic plasma concentration ranges from 0.5 to 2.5 fig/ml. These levels are obtained by doses of 200–300 mg every 6–8 hours. It is mostly metabolized by the liver and its metabolism and excretion are not significantly affected by renal failure. Mexiletine has very few deleterious drug interactions; more importantly, it does not affect digoxin blood levels. Its efficacy in controlling ventricular arrhythmias has been widely studied. The reported success rate varies from 84% to 52%. In our study of patients with symptomatic and refractory ventricular arrhythmias, the success rate with mexiletine was 55% initially and 33% at one year. Mexiletine appears to be most useful in combination with other anti arrhythmic agents such as propranolol, quinidine, procainamide, or amiodarone. Mexiletine has very few cardiac side effects. It was found not to have significant negative inotropic effects even in patients with congestive heart failure. Its major side effects, however, include gastric intolerance. Other less common side effects include central nervous system manifestations. Like all other antiarrhythmics, it can potentially aggravate ventricular arrhythmias in about 10% of patients but in most cases the proarrhythmic effect is not Clin cally significant.     

神经元型钠通道在室性心律失常发生机制中的作用

室性心律失常是导致心脏性猝死最重要的原因,其发生机制与心室肌细胞离子电流紊乱有密切关系。近期研究发现,神经元型钠通道也表达于心脏,是介导晚钠电流的重要通道,可通过以下机制触发室性心律失常:(1)神经元型钠通道活性异常增高引起内向电流增大,破坏动作电位平台期电位平衡,直接引起细胞膜去极化,发生早后除极。(2)神经元型钠通道与钙调控蛋白在T管微域内共定位,其介导的Na+内流通过增强钙调控蛋白功能引起舒张期Ca2+释放,发生迟后除极。(3)晚钠电流具有速率依赖性和分布异质性,可增大复极离散,构成功能性折返的发生基质。现就神经元型钠通道在室性心律失常发生中的作用做一综述。     

索他洛尔临床应用进展

近年来心律失常抑制试验 (CAST)研究表明 , 类抗心律失常药 (氟卡胺、恩卡胺和莫雷西嗪 )虽然能抑制心肌梗死 (MI)后病人的室性心律失常 ,但却使治疗组死亡率较安慰剂组增高。CAST研究之后 ,临床医生将兴趣转向了 类药物的研究 ,主要集中选用了胺碘酮和索他洛尔与其它多种抗心律失常药物的对比研究。本文就索他洛尔 (施太可 )近年来在临床研究方面的进展作一概述。1　电生理和药理作用索他洛尔是左旋和右旋盐酸索他洛尔的外消旋混合物 ,左旋异构体具有 类 (β阻滞 )和 类抗心律失常双重作用 ,右旋异构体主要起 类抗心律失常作用 [1]…     

Effect of Corticosteroid Therapy on Ventricular Arrhythmias in Patients with Cardiac Sarcoidosis

Background: Ventricular arrhythmias are one of the main causes of sudden death in cardiac sarcoidosis (CS). Little is known about the efficacy of corticosteroid therapy for ventricular arrhythmias in CS. Methods: Thirty‐one CS patients presenting premature ventricular contractions (PVCs, ≥300/day) were investigated. Fourteen patients had nonsustained ventricular tachycardia (NSVT). All of patients were treated with corticosteroid, and the initial dosage is 30 mg/day of prednisone, which was tapered over a period of 6 months to a maintenance dosage of 10 mg/day. Twenty‐four hour Holter monitoring, signal averaged electrocardiography (SAECG), echocardiography, gallium‐67 scintigraphy, serum angiotensin converting enzyme (ACE) and plasma B‐type natriuretic peptide (BNP) concentrations were assessed before and after corticosteroid therapy. Results: As a whole, there were no significant differences in the number of PVCs and in the prevalence of NSVT before and after steroid therapy. However, the less advanced LV dysfunction patients (EF ≥ 35%, n = 17) showed significant reduction in the number of PVCs (from 1820 ± 2969 to 742 ± 1425, P = 0.048) and in the prevalence of NSVT (from 41 to 6%, p = 0.039). Late potentials on SAECG were abolished in 3 patients. The less advanced LV dysfunction group showed a significantly higher prevalence of gallium‐67 uptake compared with the advanced LV dysfunction group (EF < 35 %, n = 14). In the advanced LV dysfunction patients, there were no significant differences in these parameters. Conclusions: Corticosteroid therapy may be effective for ventricular arrhythmias in the early stage, but less effective in the late stage. Ann Noninvasive Electrocardiol 2011;16(2):140–147     

The Effects on Cardiac Arrhythmias of Antihypertensive Therapy Causing Regression of Left Ventricular Hypertrophy

To examine the effects of antihypertensive therapy causing regression of left ventricular hypertrophy on cardiac arrhythmias, 26 hypertensive subjects were treated with ramipril with felodipine if required, and followed for 6 months after blood pressure control.Compared with baseline, left ventricular mass index (LVMI) was significantly reduced both at blood pressure control and after a further 6 months of treatment (baseline, blood pressure control, 6 months after blood pressure control; LVMI 142 ± 3.6, 131 ± 3.4, 123 ± 3.8* g/m², *P < .01 compared with baseline). There was a significant relationship between the decrease in systolic blood pressure and the decrease in LVMI after 6 months of blood pressure control compared with baseline (r = 0.41, P = .05). Compared with baseline, the average total number of ventricular ectopics decreased after blood pressure was controlled (88 ± 59 and 21 ± 12 respectively); however this reduction was not maintained after 6 months of further treatment, either before (78 ± 50) or after drug washout (86 ± 40). Compared with baseline (639 ± 590) supraventricular ectopic total was not initially reduced after blood pressure control (650 ± 604), but was reduced after a further 6 months of treatment (294 ± 261). This reduction was maintained after drug washout (267 ± 254), although this did not reach statistical significance. Radionuclide scanning at baseline was not a predictor of patients with the highest risk of arrhythmia and there was no correlation between improvement or worsening of a defect with changes in ventricular ectopic total.In conclusion, antihypertensive therapy with ramipril and felodipine, although causing regression of left ventricular hypertrophy did not lead to a sustained reduction in ventricular ectopic total.     

心室重构和室性心律失常

心室肌在受到损伤时发生的电、结构和功能的适应变化称心室重构,心室重构后室性心律失常的发生率升高了.目前研究发现,室性心律失常的发生与心室重构有关.心室重构在室性心律失常的病理生理过程中具有重要作用.抑制心室重构可能是更有效的治疗、预防心律失常的方法.