Beta blockers in arrhythmias: When and where to use?
Ajay Naik
Interventional Cardiac Electrophysiologist, the Heart Care Clinic, Ahmedabad Gujrat
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Introduction:
In 1958, Powell and Slater described the particular anti-adrenergic properties of a new compound, Dichloroisoproterenol (1). Subsequently, with the synthesis of Propranolol in 1962, which earned Sir James Black the Nobel prize for Medicine in 1989, and with the first clinical studies (1964) of the treatment of angina, arterial rhythm and hypertension disorders, this class of drugs left the experimental phase to become part of daily practice.
Of the various beta blockers (βB) (Figure 1), the commonly used drugs are sustained release Metoprolol Succinate, short acting Metoprolol tartarate, Carvedilol, Propranolol, Bisoprolol, Nebivolol and ultra-short acting Esmolol (intravenous preparation only).Metoprolol and Propranolol are commonly used via both parenteral and oral routes. Sotalol is a Class III Antiarrhythmic drug with additional beta blocking properties. Atenolol use has considerably reduced following lack of mortality benefit data from recent clinical trials.
Metabolism |
Beta I Selective |
Non-Selective |
Alpha+Beta Blockers |
Hepatic |
Metoprolol |
Propranolol |
Labetalol |
Intermediate |
Acebutolol * |
Pindolol* |
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Renal |
Atenolol |
Mepindolol* |
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The use of βB in treatment arrhythmias in various clinical situations is described in the ensuing passages. Acute presentations with hemodynamically unstable arrhythmias should be treated with cardioversion / defibrillation. Even for hemodynamically stable arrhythmias, when drug therapy is attempted, a defibrillator should be kept ready in the event of hemodynamic deterioration.
Supraventricular Tachycardia (SVT)
1. Narrow Complex Tachycardia (NCT): These arrhythmias are either AV node dependent tachycardias (AVNRT, AVRT) or AV node independent arrhythmias such as atrial tachycardia (AT), Atrial Flutter (AFL) and Atrial Fibrillation (AF).
a. AV node dependent tachycardias:
The usual mechanism is reentry with AV node as an integral part of the circuit. A temporary delay in AV nodal conduction usually terminates these tachycardias.
Acute presentation with SVT:
Commonly used drugs are Intravenous (IV) Adenosine, Esmolol, Metoprolol, Propranolol and the Calcium Channel Blockers (CCBs) Verapamil and Diltiazem. Whereas Adenosine and Esmolol act and are metabolized very fast, the other drugs act within a few minutes when given intravenously.
IV Metoprolol tartarate (1mg /ml preparation, 5 ml dose) is given over 5 minutes. It may be repeated after 5 – 10 minutes while monitoring ECG and BP.
IV Esmolol (10 mg/ml preparation) is given as a loading dose 500 mcg / kg over 1 minute, followed by 50 mcg/kg/minute infusion for 4 minutes. This may be titrated up sequentially by 50 mcg/kg/min to a maximum of 200 mcg / kg / minute. A bolus of 500 mcg/kg may be administered prior to each up-titration.
IV Propranolol hydrochloride (1 mg/ml preparation) is given as 1 mg/dose slow IV push, repeated every 5 minutes up to a total of 5 mg. Subsequent dose should be no sooner than 4 hours. IV infusion 2 – 3 mg / hr should be titrated to HR and BP.
Chronic prophylaxis against SVT:
Electrophysiology Study followed by Radiofrequency ablation is curative in most cases of SVT and this choice should be offered to the patient. Drug prophylaxis regimen would lie in a spectrum ranging from “Pill in the pocket / purse” for occasional transient episodes to lifelong multiple drug combination for episodes that require frequent hospitalizations. Frequency, duration and symptomatology during episodes will determine the prophylaxis dosage regime. Generally, sustained release preparations of Metoprolol, Propranolol, Verapamil, Diltiazem are prescribed to these patients.
Correspondence: The Heart Care Clinic, 201, Balleshwar Avenue, Bodakdev, SG Highway Ahmedabad 380015.
Tel: +91-79-26873101, Fax: +91-79-26872499,
Email: naikajay@yahoo.com
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Metoprolol tartarate 50 – 450 mg / day in 2 - 3 divided doses. Same strength of Sustained Release Metoprolol Succinate (SRMS) can be given as a single daily dose.
Propranolol is started at 20 – 40 mg twice a day (maximum 640 mg/ day). Sustained release Propranolol can be started at 40 mg daily and stepped up to 320 mg daily. This is especially preferred in the pediatriac population of arrhythmias during pregnancy or those associated with congenital heart disease.
Bisoprolol and Nebivolol are highly selective β-1 receptor blockers. In patients suffering from bronchospastic disease or dyslipidemia who have arrhythmias despite treatment with CCBs, these agents are preferred add-on drugs over the other commonly used βB.
Bisoprolol is started at 2.5 – 5 mg/day and stepped up to a maximum of 20 mg/day.
Nebivolol is started at 2.5 – 5 mg/day and stepped up to a maximum of 40 mg/day.
b. AV node independent arrhythmias (AT / AFL /AF):
For these arrhythmias, the primary goal is control ventricular rate (VR) for symptom relief. This is achieved by IV Metoprolol, Propranolol, Diltiazem or Verapamil. IV Esmolol infusions can be titrated to maintain VR and hemodynamics. IV Adenosine has no role due to its short duration of action.
Occasional cases of Paroxysmal Atrial Fibrillation (PAF) or Atrial tachycardia (AT) may terminate when being treated with IV βB to control the ventricular rate.
For long term control of ventricular rates and prevention of recurrences, the drugs used are Metoprolol, Propranolol, Verapamil, Diltiazem, Sotalol or Amiodarone. In presence of heart failure (HF), Carvedilol, Sustained release Metoprolol Succinate, Digoxin, Amiodarone and Sotalol become preferred choices.
Metoprolol dose has been outlined earlier.
Carvedilol can be started at 3.125 mg twice a day and titrated up to 50 mg twice a day.
Sotalol should be initiated and doses increased in a hospital with facilities for cardiac rhythm monitoring and assessment due to risk of proarrhythmias. The dose is 80 mg twice a day. If the initial dose does not reduce the frequency of relapses of AFL /AF and is tolerated without excessive QT prolongation (not > 520 ms) after 3 days, the dose may be increased to 120 mg twice daily. This can be stepped up to a maximum of 160 mg twice daily.
B. Ventricular Tachyarrhythmias (VT)
VT may be Idiopathic (structurally normal heart), due to primary electrical disease (e.g. Brugada syndrome) or associated with structural heart disease (pump dysfunction associated with CAD or myocardial disease).
1. Idiopathic VT such as RV outflow tract tachycardia (RVOTT) or Idiopathic LV tachycardia (ILVT) can be treated with IV Verapamil or Metoprolol. These arrhythmias are amenable to permanent cure by RF ablation. Chronic prophylaxis is by Verapamil, Metoprolol or Sotalol.
2. Post-MI scar VT: VT in patients with old Myocardial infarction is typically monomorphic in nature and occurs due to scar-related reentrant mechanism. The management plan includes revascularization if indicated, AICD implantation, beta blockers, antiarrhythmic drugs (AAD) if needed (viz. Amiodarone, Sotalol) and optimization of CAD and HF medications. The βB used are Sustained release Metoprolol Succinate (SRMS) and Carvedilol.
3. Acute ischemia/MI with VT is usually polymorphic. The management is emergency cardioversion / defibrillation, relief of ischemia by revascularization (PTCA / CABG) and βB therapy. IV βB therapy (Metoprolol / Esmolol) is life-saving in this setting.
4. VT in primary electrical syndromes (e.g. Brugada syndrome, Idiopathic VF) is difficult to manage with medications. AICD and βB are the mainstay of management.
C. Sudden Cardiac Arrest (SCA) survivors
SCA survivors need to be carefully evaluated for etiology. Apart from revascularization if indicated, the mainstay of therapy is AICD, βB and AADs. The βB used are generally SRMS or Carvedilol.
D. βB in management of VT storms
Electrical storm or VT storm refers to a situation when rapid clustering of episodes of malignant ventricular tachyarrhythmias develops requiring repetitive attempts at cardioversion. The presentation may be:
1. Cluster of VT/VF (e.g., defined as 2 or 3 or more VT episodes per 24 hour period),
2. Electrical storms (e.g., rapid clustering of VT/VF episodes), or
3. Incessant VT (characterized by episodes that last > 50% of the time)
There may be multiple potential underlying mechanisms. It is of utmost importance to try and understand the substrate of incessant arrhythmias because if a diagnosis is established, a targeted treatment may be possible. It may occur in the clinical setting of:
1. Acute coronary syndrome (ACS),
2. Acute decompensated heart failure,
3. In victims of out-of-hospital cardiac arrest in whom VT/VF is the mechanism
4. Patients with an implanted AICD (for various indications)
The morphologies of VT may be:
1. Monomorphic (Post MI scar related, Dilated Cardiomyopathy)
2. Polymorphic (Acute ischemia, Primary electrical syndromes)
3. Torsade de pointes (QT prolongation due to drugs or congenital LQTS)
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The management may include some or all of the following : External Cardioversion / Defibrillation, IV βB, AADs, IV Magnesium sulfate, correction of dyselectrolytemia, sedation, transvenous pacing for ATP or bradycardia prevention, emergency Radiofrequency ablation, IABP support, revascularization where indicated, External cardiopulmonary support and finally, AICD implantation after stabilization. βB would probably be required life-long for these patients.
IV βB (Metoprolol / Esmolol) should always be considered in treatment of polymorphic VT storm as it is the single most effective therapy.
E. βB in management of Atrial Fibrillation (AF):
The focus on management varies as per nature of presentation. Need for anticoagulation should be evaluated for each patient by CHADS2 score system.
1. Paroxysmal AF (PAF): During acute presentations, the fast ventricular rate (VR) can be controlled by IV βB (Metoprolol / Esmolol). PAF may terminate by the “Pill in the pocket / purse” approach of taking an oral IC AAD (Propafenone / Flecainide) or IV βB or Amiodarone. Catecholaminergic AF episodes may terminate acutely with IV βB. Prevention of recurrences is by chronic oral βB, CCBs or Amiodarone therapy.
2. Persistent or Chronic AF: Acute presentations are generally due to fast VR or CHF due to underlying disease or Tachycardiomyopathy. The focus is on controlling VR (IV βB, Amiodarone). Attempts to restore Sinus rhythm would also involve longer term use of Class III AAD and oral βB. Some patients may require multiple drugs (βB, Digoxin, CCBs, Amiodarone) for controlling VR. Possibility of co-existing underlying conduction system disease should be borne in mind when combining these medications. Repeated hospitalizations for fast VR or CHF should merit consideration for AV node ablation and pacemaker / CRT implantation.
F. βB in management of arrhythmias during pregnancy
Hemodynamic and fluid alteration may change the presentation of arrhythmias during pregnancy. In order to prevent any untoward effects on the fetus, prescription of medications is conventionally minimized. Adenosine is drug of choice for acute presentations of SVT (2). Chronic prophylactic therapy is avoided in pregnancy where possible. If required, Verapamil, Propranolol, Metoprolol and Digoxin are preferred. In the event of life-threatening arrhythmias, maternal health gains preference and AADs may need to be used with knowledge of risk to the fetus, especially in the first trimester. DC shock to the mother has virtually no untoward effect on the fetus.
G. βB in management of arrhythmias in the pediatric population and associated congenital heart disease:
βB and Amiodarone are the mainstay of arrhythmia management in CHD. They are used in most of the serious arrhythmias – VT, post surgical ventricular and Supraventricular arrhythmias, Post Fontan surgery arrhythmias, unstable SVTs. Recurrent SVTs may be treated with IC AADs, βB, CCBs or by RF ablation.
H. βB in management of Long QT syndrome (LQTS):
βB are the single most important class of drugs that have shown demonstrably lower mortality in LQTS patients (4).
Acute presentation with Torsade de pointes is treated with DC shock, IV βB, IV Magnesium sulfate, Temporary pacing.
Chronic therapy includes AICD implantation with oral βB at maximally tolerated dosage. Recurrent TDP or frequent shocks may prompt the option of sympathetic ganglionectomy – however this has promising results only in select centers with good surgical experience (3).
I. βB in management of arrhythmias in CHF and cardiomyopathies (CMP)
βB, Amiodarone and Sotalol are the mainstay of arrhythmia management in CHF and CMP. SRMS and Carvedilol have both shown to reduce risk of SCA and mortality in patients with CHF. Need for AICD and Cardiac Resynchronization Therapy (CRT, biventricular pacing) should be evaluated.
J. βB in management of post-cardiac surgery arrhythmias
Pre-operative institution of βB results in lesser incidence of post-operative arrhythmias (4). Patients with LV dysfunction undergoing cardiac surgery are at high risk of VT. IV βB, Amiodarone, Temporary Atrial and Ventricular pacing are options to be considered in these patients.
Summary:
Beta blockers are in the forefront of arrhythmia management armamentarium. Their use has conclusively shown morbidity and mortality reduction in high risk population. Numerous agents are available with varying duration of action, route of administration and receptor affinity. The beta blocker used should be judiciously selected with due consideration to the patient demographic, nature of disease, type of arrhythmia and clinical presentation.
References:
1. Menghini F. The role of beta-blocker therapy in the treatment of arterial hypertension. Hypertension 1996 : One Medicine, Two Cultures.
2. Joglar JA, Page RL. Antiarrhythmic drugs in pregnancy. Curr Opin Cardiol 2001, 16: 40-45.
3. Wang L, Feng G. Left cardiac sympathetic denervation as the first-line therapy for congenital long QT syndrome. Medical Hypotheses 2004; 63 (3): 438-441.
4. Mayson SE, Greenspan AJ, Adams S, Decaro MV, Weitz HH, Whellan DJ. The changing face of postoperative atrial fibrillation prevention: a review of current medical therapy. Cardiol Rev. 2007; 15(5): 231-241.
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