Pharmacologic approach to therapy of Brugada syndrome: quinidine as an alternative to ICD therapy?
Pharmacologic approach to therapy of Brugada syndrome: quinidine as an alternative to ICD therapy?
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DOI：
10.1002/9780470994900.ch18
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发表时间：
2005-01-01
期刊：
影响因子：
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通讯作者：
Viskin, S
中科院分区：
文献类型：
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作者：
Belhassen, B;Viskin, S
1992年，西班牙心脏病学家兄弟Pedro和Josep Brugada报告了8例心脏骤停流产的患者，均表现为窦性心律右束分支传导阻滞（RBBB），心前导联V1-V3 ST段显著抬高。[1]尽管最初对诊断存在争议，特别是关于轻微的致心律失常性右心室发育不良的可能性，但由于临床、心电图（ECG）和电生理（EP）特征一致，右心室反复受累沿着消失，使心脏病学界确信Brugada综合征实际上是表面健康患者心源性猝死的一个新的重要原因。2自20世纪90年代中期以来，医生的认识不断提高，导致全世界报告的患者数量不断增加。1998年，Chen及其同事首次确定Brugada综合征是一种常染色体显性遗传的遗传性疾病。3这些研究者描述了突变，所有突变都影响3号染色体上的心脏钠通道SCN 5A。这种疾病似乎是遗传异质性的，因为目前，SCN 5A仅在30%的患者中被证实参与。最近，在3号染色体上发现了一个新的基因位点，与SCN 5A不同。4该疾病传播的遗传模式导致心脏骤停幸存者家庭中发现更多受该疾病影响的无症状患者。3-5尽管Brugada综合征的临床和遗传学诊断仍存在一些悬而未决的问题，但在过去十年中，关于其管理已经取得了重大进展。全世界大多数电生理学家都建议在Brugada综合征症状患者（心脏骤停幸存者、不明原因晕厥）以及程控心室刺激（PVS）期间诱发室颤（VF）的高风险无症状患者中植入自动心律转复除颤器（ICD）。这种态度是ICD在终止VF方面的非凡功效以及该领域权威人士一再声称“没有药物在预防Brugada综合征的心源性猝死方面显示出功效”的逻辑结果。6事实上，虽然大多数抗心律失常药物（如胺碘酮和β受体阻滞剂）被发现无效甚至有害，7，8有初步证据表明，少数药物实际上可能对Brugada综合征有有益作用，特别是奎尼丁，我们在本机构常规使用该药治疗恶性特发性室性快速性心律失常超过20年。
In 1992, Pedro and Josep Brugada, two Spanish cardiologist brothers, reported 8 patients with aborted cardiac arrest and no demonstrable heart disease who exhibited in sinus rhythm right bundle branch block (RBBB) with prominent ST segment elevation in precordial leads V1–V3. 1 Despite initial controversy about the diagnosis, especially concerning the possibility of a subtle arrhythmogenic right ventricular dysplasia, the repeated lack of right ventricular involvement along with consistent clinical, electrocardiographic (ECG) and electrophysiologic (EP) features convinced the cardiologic community that the Brugada syndrome was actually a new and important cause of sudden cardiac death in ostensibly healthy patients. 2 Since the mid-1990s, an increased awareness among physicians has resulted in a growing number of patients reported worldwide. In 1998, Chen and associates were first to establish that the Brugada syndrome was a genetic disease with an autosomal dominant pattern of transmission. 3 These investigators described mutations, all affecting the cardiac sodium channel SCN5A on chromosome 3. 3 The disease appears to be genetically heterogeneous because, at present, SCN5A has a proven involvement in only 30% of patients. More recently, a novel gene locus on chromosome 3, distinct from SCN5A, has been identified. 4 The genetic pattern of transmission of the disease has lead to the increased detection of asymptomatic patients affected by the disease among families of cardiac arrest survivors. 3–5 Despite the fact there are still unanswered issues dealing with the clinical and genetic diagnosis of the Brugada syndrome, major advances have been accomplished during the last decade concerning its management. Implantation of an automatic cardioverter-defibrillator (ICD) has been recommended by most electrophysiologists worldwide in symptomatic patients with Brugada syndrome (cardiac arrest survivors, unexplained syncope) as well as in high-risk asymptomatic patients who have inducible ventricular fibrillation (VF) during programmed ventricular stimulation (PVS). Such an attitude is a logical consequence of both the extraordinary efficacy of ICD in terminating VF and the repeated claim of authorities in the field that ‘No drug has shown efficacy in the prevention of sudden cardiac death in the Brugada syndrome.’6 In fact, while most antiarrhythmic agents (such amiodarone and β blockers) have been found to be ineffective or even deleterious, 7, 8 there is preliminary evidence that a few drugs may actually have a beneficial effect on the Brugada syndrome, especially quinidine, a drug we have used routinely for more than two decades in our institution in the management of malignant idiopathic ventricular tachyarrhythmias.