Download ICD电风暴药物优化治疗新疆医科大学一附院心脏中心汤宝鹏ICD电

ICD电风暴药物优化治疗
新疆医科大学一附院心脏中心
ICD电风暴
Nademanee：近期MI发生≥20/d；或每h≥4次VT/VF
Credner:24h内发生需ICD干预≥3次的VT/VF事件
AVID试验：24h内出现≥3次互不相连的VT/VF事件，
每次事件相隔≥5min
• 24 h内出现≥3次的互不相连的需要ICD进行干预的VT／VF事件，每
次事件相隔≥5 min (AVID研究)
Time between arrhythmias < 1 hr for 83% inter-detection
intervals
对于无休止的VT或VF，ICD治疗后即使只有1跳正常心跳，也有学
者认为应包括在电风暴范畴
ACC、AHA、ESC，2006年室性心律失常的诊疗和SCD预防指南
电风暴发作
电风暴发作
ICD电风暴的发生率
电风暴的发
生率报告尚
不一致，国
内尚无统计
资料，国外
多为ICD患者
的相关资料，
发生率一般
介于10%～
二级预防的发生率为10～60％，如果用AVID研究的定义，
随访1～3年，二级预防：发生率为10～28％，一级预防：发
生率为4％（MADIT II）
25%之间
电风暴发生的季节性
ICD电风暴—机制
• ICD对心肌的损伤
– 多次电击导致肌钙蛋白升高，恶化心律失常基质，增加心律失常易感
性
• ICD放电的致痛性和交感神经激活
– ICD放电引起患者疼痛、恐惧或焦虑等会使中枢交感神经过度激活，使
ICD电风暴常有反复发生趋势，形成ICD介导的电风暴
• ICD误识别放电
– 快速房颤、ICD功能异常及电磁干扰等
CRT-D术后的电风暴--左室心外膜起搏所致
--增加复极离散度，早后除极，多形性VT
---起搏引起折返性单形性VT
发生在植入后早期，需关闭左室起搏或行RFCA
电风暴的具体治疗措施
去除病因及诱因
1：血运重建\纠正心力衰竭
2：纠正电解质紊乱及酸碱失
衡
3：镇静
4:驱除医源性致病因素
•静脉使用抗心律失常药物
– 胺碘酮、 β受体阻滞剂仍然是治疗ES的主要药物
•镇静和抗焦虑
– 过度的紧张易导致呼吸性碱中毒，并引起低钾，更易诱发VT/VF
，从而形成恶性循环。国外有报道，对于ES非常顽固的患者应
用全身麻醉，收到不错效果
•ICD进行超速起搏
•左侧星状神经节阻断术
•导管消融
Management of Electrical Storm
Medical Therapy
Brugada的电风暴应首选异丙
Beta blockade – for ischemic heart dz
对原发性短QT可选用奎尼丁
Amiodarone – widely used for everyone
,氟卡尼或维拉帕米,对难治
Lidocaine – best for acute ischemia
电风暴可选用溴苄铵。
Class III agents – Ibutilide off label
Class IA – procainamide, quinidine – may slow VT
Management After Storm
• Sedation and Post Traumatic Stress
–
–
–
–
Poor QOL after shocks
Fear of activity/social situations
Anxiety/depression – medical Rx
Phantom Shocks（幻觉电击）/”Afraid to go to sleep” –
reassurance
– Request removal of device – reassurance
β -Blockers
Effects of Beta-Blockers on Implantable Cardioverter Defibrillator Therapy
and Survival in the Patients with Ischemic Cardiomyopathy
(from the Multicenter Automatic Defibrillator Implantation Trial-II)
survival in 691 patients who received ICDs
In the Multi-center Automatic Defibrillator Implantation Trial-II.
258 patients who were
not receiving blockers
433 who were receiving β-blockers
metoprolol (n=192),
atenolol (n= 58), carvedilol (n=182).
Follow up 4 years
Study population: Details of the MADIT-II protocol have been described previously.MADIT-II was a
prospec-tive, randomized trial involving patients who had previous myocardial infarctions and
ejection fractions ≤30%. Of the 1,232 patients who were enrolled in the study, 742 were randomized
to receive ICDs, whereas the remainder (490) received conventional medical therapy. Seven
hundred twenty of 742 patients randomized to defibrillator therapy received ICDs.
Am J Cardiol 2005;96:691– 695
Baseline
Clinical characteristics by β-blocker dose in 691 patients who received ICDs
Am J Cardiol 2005;96:691– 695
Am J Cardiol 2005;96:691– 695
Am J Cardiol 2005;96:691– 695
Result
Conclusion:β-blockers reduce the risk for VT or VF
and improve survival in ICD-treated patients with
ischemic cardiomyopathy. had a 52% relative risk
reduction for recurrent ven-tricular
tachycardia/ventricular fibrillation requir-ing ICD therapy
compared with those who did not take β -blockers
Am J Cardiol 2005;96:691– 695
Treating Electrical Storm Sympathetic Blockade Versus
Advanced Cardiac Life Support–Guided Therapy
EF<35% MI
There are no statistically significant differences in any variable
Circulation . 2000;102:742-747
Treating Electrical Storm Sympathetic Blockade Versus Advanced
Cardiac Life Support–Guided Therapy
Circulation . 2000;102:742-747
右美托咪定联合倍他乐克拮抗交感活性亢进的临床研究
选择交感风暴患者97例 男63 例，女34例，随机分为对照组、倍他乐克组、右美托咪定组
、倍他乐克+右美托咪定联合治疗组联合治疗组相比其他组，交感电风暴发生率最低（
P<0.05)，血浆NE、E明显下降（P<0.05),交感活性最低，血流动力学CO、CI、EVLWI及
血浆BNP明显下降（P<0.05)，心功能恢复最好。右美托咪定联合倍他乐克可有效抑制交
感活性，治疗交感风暴效果最佳。
实用药物与临床2013年16卷9期
Conclusions
• Sympathetic blockade is superior to the antiarrhythmic therapy
recommended by the ACLS guidelines in treating ES patients. Our
study emphasizes the role of increased sympathetic activity in the
genesis of ES. Sympathetic blockade -not class Ⅰ antiarrhythmic
drugs -should be the treatment of choice for ES.
• β -Blockade has a fundamental role in the management of electrical
storm, especially with the use of b -blockers which antagonize both b 1
and b 2 receptors; it has been shown to increase the fibrillation
threshold and decrease the incidence of sudden death
• Even in electrical storm patients already on oral b -blocker therapy,
adding β–blockers intravenously may help further to suppress the electrical storm episode
Circulation . 2000;102:742-747
Cardiovasc. Ther. 9(8), 1051–1058 (2011)
Amiodarone
Comparison of -Blockers, Amiodarone Plusβ-Blockers, or Sotalol for
Prevention of Shocks From Implantable Cardioverter Defibrillators
The OPTIC Study : A
Randomized Trial
they had received dualchamber ICD within 21 days before randomization Patients had to have sustained VT,
VF, or cardiac arrest (not within 72 hours of acute myocardial infarction) and a left ventricular ejection fraction
of 40% or lower, inducible VT or VF by programmed ventricular stimulation with a left ventricular ejection
fraction of 40% or lower, or unexplained syncope with VT or VF, inducible by programmed stimulation.
JAMA. 2006;295:165-171
baseline
JAMA. 2006;295:165-171
Result
Outcome Events of the 3 Treatment Assignments
Abbreviations: ATP, antitachycardia pacing therapy; CI, confidence interval; HR, hazard ratio.
*In the -blocker and sotalol groups, some patients had both appropriate and inappropriate shocks
JAMA. 2006;295:165-171
JAMA. 2006;295:165-171
Shock Frequency During 1 Year of F ollow-up*
*Because of rounding, percentages may not all total 100. Two patients assigned to the
group and 1 patient assigned to the amiodarone plus -blocker group are not
included because they had no follow-up
-blocker
JAMA. 2006;295:165-171
Adverse Events of the 3 Treatment Assignments
*For any difference between 3 treatment assignments.
JAMA. 2006;295:165-171
Conclusions
Amiodarone has been widely used for the treatment of
electrical storm. The Optimal Pharmacologic
Despite use of advanced ICD technology and treatment
with aβ-blocker, shocks occur commonly in the first year after
ICD implant
Amiodarone plus β-blocker is effective for preventing these
shocks and is more effective than sotalol but has an increased
risk of drug-related adverse effects.
intravenous amiodarone may be an effective drug even in
patients already receiving chronic oral amiodarone
Sotalol
PREVENTION OF IMPLANTABLE-DEFIBRILLATOR SHOCKS BY
TREATMENT WITH SOTALOL
302 patients
treatment with 160 to 320 mg of
sotalol per day (151patients)
matching placebo (151 patients)
followed for 12 months
a history of life-threatening ventricular tachyar-rhythmias that were
not due to a reversible cause; had received their first or a
replacement implantable cardioverter–defibrillator within three
months before enrollment
N Engl J Med 1999;340:1855-62.
Baseline
N Engl J Med 1999;340:1855-62.
Time to Death from Any Cause or the Delivery of a First
Shock for Any Reason, According to the Intention to Treat
N Engl J Med 1999;340:1855-62.
Sotalol
• Conclusions:sotalol has been shown to significantly
decrease the recurrences of ventricular
tachycardia/ventricular fibrillation, all-cause ICD shocks,
and all-cause death
• In the OPTIC study,sotalol compared with a regular b blocker only tended to reduce ICD shocks, but this effect
did not reach statistical significance
• Two other small studies did not observe a significant
difference in either mortality or recurrent ventricular
tachycardia/ventricular fibrillation requiring ICD therapies
attributable to sotalol, and sotalol was not superior to
metoprolol
Kettering K, et al. Efficacy of metoprolol and sotalol in the prevention of recurrences of sustained ventricular tachyarrhythmias in
patients with an implantable cardioverter defibrillator. Pacing Clin Electrophysiol 2002; 25:1571–1576.
Seidl K, et al. Comparison of metoprolol and sotalol in preventing ventricular tachyarrhythmias after the implantation of a
cardioverter/ defibrillator. Am J Cardiol 1998; 82:744–748.
Azimilide
Azimilide (阿齐利特）Reduces Emergency Department Visits
and Hospitalizations in Patients With an Implantable
Cardioverter-Defibrillator in a Placebo-Controlled Clinical Trial
A total of 633 patients with an ICD were randomized in the SHIELD
Randomization was conducted in a ratio of 1:1:1
placebo
Azimilide 75 mg once daily
Azimilide 125 mg once daily
Patients were followed and maintained on the
originally as-signed blinded therapy for 365 days
J Am Coll Cardiol 2008;52:1076–83
Baseline
J Am Coll Cardiol 2008;52:1076–83
J Am Coll Cardiol 2008;52:1076–83
Azimilide
• Conclusions:Azimilide significantly reduces the number
of ED （Emergency Department ） visits and
hospitalizations in patients with an ICD at high risk of
arrhythmias.
• In the SHIELD study, the 75 and 125 mg dose of azimilide
significantly reduced the recurrence of shocks plus
symptomatic arrhythmias treated by ATP. It also reduced
emergency department visits and hospitalizations in
patients with ICDs
Dorian P, Al-Khalidi HR, Hohnloser SH, et al. Azimilide reduces emergency
department visits and hospitalizations in patients with an implantable cardioverterdefibrillator in a placebo-controlled clinical trial. J Am Coll Cardiol 2008;52:1076–1083.
Electrical storm in patients with an implantable
defibrillator: incidence, features, and preventive therapy:
insights from a randomized trial
A total of 148 patients (23%) out of 633 patients of
SHIELD randomized experienced at least one ES
58 (27%) were on placebo 51(23%) on 75 mg azimilide
39 (20%) on 125 mg azimilide
after 7 (2 – 12.3) months of median (IQR) follow-up
This study is a prospectively designed secondary analysis of SHIELD
Conclusion:1:Compared with placebo,azimilide (75 and 125 mg/day) reduced the
risk of recurrent ES by 41% (HR =0.63, 95% CI 0.35 – 1.11,P = 0.11) and 55% (HR =
0.45, 95% CI 0.23 – 0.87, P = 0.018), However,
2:the reduction in time-to-first ES did not reach statistical significance by
both doses (75 and 125 mg)
European Heart Journal (2006) 27, 3027 –3032
European Heart Journal (2006) 27, 3027 –3032
Conclusions
• However, in a prospective study , of the 148
patients who experienced at least one episode of electrical
storm, azimilide did not significantly reduce the number of
patients with electrical storm.
Of note, Torsade de pointes (TdP) associated with azimilide
treatment was documented in five patients (1.2%)
• It was shown to be effective in increasing the median time to
first all-cause ICD shocks in a study
Dofetilide
Efficacy and Safety of Dofetilide in the Treatment of Frequent Ventricular
Tachyarrhythmias After Amiodarone Intolerance or Failure
Eighteen patients were included in the study
patients had a history of coronary artery disease,
average left ventricular ejection fraction was 30%,
all received the ICD for secondary prophylaxis.
In the 90 days preceding dofetilide initiation,
patients had a median of 11 VT/VF episodes and 1.5 shocks from the ICD
The primary end point : the total number of VT/VF episodes.
Secondary end points : mortality, number of total shocks, appropriate shocks,
electrical storm, hospitalization, and drug discontinuation.
One small study supported efficacy and safety of dofetilide in the treatment of
frequent ventricular tachycardia/ventricular fibrillation after amiodarone intolerance
or failure .
Combinations of antiarrhythmic drugs
There has been no randomized study comparing treating ventricular
tachycardia with combinations of antiarrhythmic drugs;
1: however, some cases and clinical experience have been reported.
Mono-therapy with class I drugs for the prevention of ventricular
arrhythmia does not appear to be well tolerated But, it has been used with
the combination of class III drugs .
2: Theoretically, the combination of a class I drug (with the exception of a
class Ic) and dofetilide might have comparable effects to amiodarone plus
b-blocker therapy. Some studies have suggested a beneficial effect from
the combination of mexiletine and amiodarone and procainamide or
quinidine with D,L,-sotalol.
3: No randomized trial has compared these drug regimes,however. If
mexiletine, procainamide, or quinidine are combined with amiodarone,
their doses should be reduced in order to avoid side-effects
Summary
• Electrical Storm not uncommon in ICD patients
• VT recurrences tend to cluster in ICD patients
• Most Storms without identifiable cause but heart
failure, ischemia and metabolic abnormalities
should be considered
• Medical management usually effective
• Storm probably associated with increased
subsequent mortality, aggressive management
may be indicated