B P7 C64 Therapy for Cardiac Arrhythmias Flashcards
The commonly used classification (_____) is still a useful framework for categorizing drug action but is limited because it is based on the electrophysiologic effects exerted by an arbitrary concentration of the drug, generally on a laboratory preparation of normal cardiac tissue.
Vaughan Williams
A more realistic but not widely used framework regarding AADs is provided by the “_____.” This approach to drug classification is an attempt to identify the mechanisms of a particular arrhythmia, to determine the vulnerable parameter of the arrhythmia most susceptible to modification, to define the target most likely to affect the vulnerable parameter, and then to select a drug that will modify the target
Sicilian Gambit
This class includes drugs that block the HCN channel mediated pacemaker current (If). Inhibition of the If channel (or “funny” current) _____
Class 0
Reduces:
Depolarization rate of the SN pacemaker cells
HR
___________ predominantly block the voltage gated fast sodium channel (INa)
Class I drugs
This class includes drugs that reduce V max (rate of rise in action potential upstroke [phase 0]) and prolong the action potential duration; onset and offset intermediate (<5 secs)
Class 1A - DOUBLE QUARTER POUNDER
Disopyrsmide
Quinidine
Procainamide
Class IA includes drugs that _____—quinidine, procainamide, and disopyramide.
Vmax: Reduce
APD: Prolong
This class of drugs does not reduce V max and shortens the APD; kinetics of onset and offset of these drugs in blocking the sodium channel is rapid (<500 milliseconds).
Class IB - LETTUCE, POTATO, MAYO, TOMATO
Lidocaine, Phenytoin, Mexelitine, Tocainide
Class IB drugs _____—mexiletine, phenytoin, and lidocaine.The kinetics of onset and offset of these drugs in blocking the sodium channel is rapid (<500 milliseconds)
Vmax: No reduction
APD: Shortens
This drugs reduce V max slow conduction velocity, and prolong refractoriness minimally. These drugs have slow onset and offset kinetics (10 to 20 seconds).
Class IC
MORE FRIES PLEASE
Moricizine
Flecainide
Propafenone
Class IC drugs, including flecainide and propafenone, can reduce V”max slow conduction velocity, and prolong refractoriness minimally. These drugs have slow onset and offset kinetics (10 to 20 seconds).
Vmax: Reduce
Slow conduction velocity
Refractoriness: prolong
Preferentially inhibits the late Na + current affecting APD and recovery and increases refractoriness and repolarization reserve; cause a reduction in early afterdepolarization-induced triggered activity.
Class ID
Ranolazine
Class ID drugs includes ranolazine, which preferentially inhibits the late Na+ current affecting APD and recovery and increases refractoriness and repolarization reserve.Class ID drugs cause a reduction in early afterdepolarization-induced triggered activity.
Refractoriness, Repolarization reserve: Increased
Drugs that block beta-adrenergic receptors
Propranolol, metoprolol, nadolol, carvedilol, nebivolol, and timolol.
This class of drugs predominantly blocks potassium channels (e.g., IKr) and prolongs repolarization.
Class III - “SAID”
Sotalol
Amiodarone
Ibutilide
Dronedarone
This class of drugs predominantly blocks potassium channels (e.g.,Ikr ) and prolongs _____. Included are sotalol, amiodarone, dronedarone, and ibutilide
Repolarization: prolong
This class of drugs predominantly blocks the L-type or slow calcium channel (ICa.L)
Class IV
Verapamil
Diltiazem
Examples of arrhythmias based on: Automaticity
Enhanced normal:
Inappropriate sinus tachycardia
Abnormal:
Atrial tachycardia
Accelerated Idioventricular rhythms
Examples of arrhythmias based on: Triggered activity
EAD: TdP
DAD:
Digitalis-induced arrhythmias
RVOT VT
Examples of arrhythmias based on: Reentry—Na+ Channel Dependent
Long excitable gap:
Sustained uniform VT
Atrial flutter (Typical)
Circus movement in WPWs
Short excitable gap:
Polymorphic and uniform ventricular tachycardia
Atrial flutter (Atypical)
Atrial fibrillation
Circus movement tachycardia in WPW
Bundle branch reentry
Ventricular fibrillation
Examples of arrhythmias based on: Reentry—Ca2+ Channel Dependent
AVNRT
Circus movement tachycardia in WPW
Verapamil-sensitive ventricular tachycardia
Some drugs exert greater inhibitory effects on the upstroke of the action potential at more rapid rates of stimulation and after longer periods of stimulation, a characteristic called ___________________
Use dependence
Drugs with this property depress V max to a greater extent after the channel has been “used” (i.e., after action potential depolarization rather than after a rest period).
Agents with class IB action exhibit rapid binding and unbinding from their receptor site on the channel protein, or exhibit use-dependent block of the fast channel at fast rates
With increased time spent in diastole (slower rate), a greater proportion of receptors unbind drug, and the drug exerts less effect.
Some drugs exert greater effects at slow rates than at fast rates, a property known as ___________________
Reverse use dependence
This is particularly true for drugs that lengthen repolarization; in the ventricle the QT interval becomes more prolonged at slow rather than at fast rates
_______________ depends critically on the interrelationships between refractoriness and conduction velocity, the presence of unidirectional block in one of the pathways, and other factors that influence refractoriness and conduction, such as excitability
Reentry
An effective agent that can stop reentry that is already present or can prevent it from starting if the drug _____________ or, alternately, ___________________
Depresses conduction
Improves conduction
Improving conduction can (1) eliminate unidirectional block so that reentry cannot begin or (2) facilitate conduction in the reentrant loop so that the returning wavefront reenters too quickly, encounters cells that are still refractory, and is extinguished
A drug that depresses conduction can transform unidirectional block into bidirectional block and thus terminate reentry or prevent it from starting by creating an area of complete block in the reentrant pathway.
A drug that slows conduction without producing block or significantly lengthening refractoriness can actually promote reentry.
If a drug prolongs the refractoriness of fibers in the reentrant pathway, the pathway may not recover excitability in time to be depolarized by the reentering impulse, and reentrant propagation ceases.
Examples of idiosyncratic adverse drug effects
Amiodarone pulmonary fibrosis and some arrhythmias, such as quinidine-induced TdP
Genetic variants can underlie susceptibility to idiosyncratic reactions.
Drugs that care considered safe in pregnancy
Adenosine (C)
Propranolol (C)
Metoprolol (C)
Lidocaine (B)
Digoxin * (C)
Sotalol (B)
Verapamil (C)
Antiarrhythmic drugs contraindicated in pregnancy
Amiodarone
Dronedarone
Proarrhythmia can manifest as _____.
(1) Increase in frequency of a preexisting arrhythmia
(2) Sustaining of a previously non-sustained arrhythmia (even making it incessant)
(3) Development of arrhythmias that the patient has not previously experienced
Electrophysiologic mechanisms of proarrhythmia are probably related to:
(1) Prolongation of repolarization or an increase in transmural dispersion
(2) Development of EADs with resultant TdP
(3) Alterations in reentry pathways to initiate or sustain tachyarrhythmias
Proarrhythmic events can occur in as many as _____% of patients receiving antiarrhythmic agents; heart failure increases this risk
5% to 10%
_____identify patients who experience AAD-induced ventricular fibrillation (VF)
Reduced LV function
Treatment with digitalis and diuretics
Bradycardia
Longer pretreatment QT interval
In the _____ Trial, however, researchers found that encainide and flecainide reduced spontaneous ventricular arrhythmias but were associated with a total mortality of 7.7%, versus 3.0% in the placebo group. Deaths were equally distributed throughout the treatment period, indicating that another type of proarrhythmic response can occur sometime after the beginning of drug therapy.
Cardiac Arrhythmia Suppression Trial (CAST)
________ blocks several channels, including the rapid inward sodium channel (INa ), IKr , Ito , and to a lesser extent the slow inward calcium channel, IKs , and the adenosine triphosphate (ATP)–sensitive potassium current (KATP ). Quinidine causes alpha-adrenergic and cholinergic blockade
For tx of primary (idiopathic) VF, ventricular arrhythmias in patients with Brugada syndrome and short-QT syndrome
Quinidine
Oral dose - 300 to 600 mg four times daily
LD: of 600 to 800 mg produces an earlier effective concentration
Adverse effects:
Prolongation of the QRS duration or as sinoatrial (SA) or AV nodal conduction; syncope as a result of self-terminating episode of TdP; prolongs the QT interval in most patients (not dose related)
Quinidine induces vasodilation by blocking alpha-adrenergic receptors and can cause significant hypotension. It does not cause significant direct myocardial depression.
Syncope - the first 2 to 4 days
Inidcations for using Quinidine
Primary (idiopathic) VF
Ventricular arrhythmias in patients with BrS
Short-QT syndrome
Quinidine crosses the placenta so it can be used to treat fetal arrhythmias
The most common adverse effects of chronic oral quinidine therapy are _____.
Gastrointestinal (GI) and include nausea, vomiting, diarrhea, abdominal pain, and anorexia (milder with the gluconate form)
Quinidine prolongs the QT interval in most patients (not dose related), regardless of whether ventricular arrhythmias occur, but significant QT prolongation (QT interval of _____ milliseconds) is often a characteristic of patients with quinidine-related syncope, who may have a genetic predisposition underlying such a response
500 to 600 msec
Therapy of proarrhythmia due to Quinidine requires immediate discontinuation of use of the drug; magnesium given intravenously _____ is the initial drug treatment of choice
Magnesium 2 g over 1 to 2 minutes, followed by an infusion of 3 to 20 mg/min
_____ can be used to suppress the ventricular tachyarrhythmia, perhaps by suppressing EADs. When pacing is not available, _____ can be given with caution
Atrial or ventricular pacing
isoproterenol
__________________ predominantly blocks the inactivated state of INa . It also blocks IKr , IK1 , and IK.ATP . Like quinidine, procainamide usually prolongs the ERP more than it prolongs the APD and thus may prevent reentry. Procainamide exerts the least anticholinergic effects among type IA drugs.
Procainamide
Convert recent-onset AF to sinus rhythm; can block conduction in the accessory pathway of patients with Wolff Parkinson-White (WPW) syndrome
Can depress myocardial contractility
Dose - IV 10 to 15 mg/kg are used at a rate of up to 50 mg/min until the arrhythmia has been controlled; oral 3- to 4-hour dosing interval at a total daily dose of 2 to 6 g
AE: rash, myalgia, digital vasculitis, and Raynaud phenomenon, fever and agranulocytosis, systemic lupus erythematosus (SLE)-like syndrome (reversible; but if positive anti-DNA antibody g ally indicates that drug therapy should be discontinued), brain and kidneys are typically spared, and there is no predilection for women.
Indications of using Procainamide
SVT
VT
Conversion of recent-onset AF to SR
AF with RVR
WPWs
Administered during an EPS to stress the His-Purkinje system and evaluate the need for a pacemaker
The drug also has diagnostic applications when given intravenously (10 mg/kg over 5 to 10 minutes). In patients with suspected Brugada syndrome who have a normal resting electrocardiogram (ECG), drug infusion can result in the characteristic _____, whereas in patients with WPW syndrome, the drug can cause _____.
BrS: “Brugada sign”
WPWs: Sudden loss of preexcitation
In patients with sinus node dysfunction, however, procainamide can prolong sinus node recovery time and worsen symptoms in some patients with _____.
Bradycardia-tachycardia syndrome
As with quinidine, prior treatment with _____ is recommended to prevent acceleration of the ventricular response during atrial flutter or fibrillation after procainamide therapy
Beta or calcium channel blockers
In _____% of patients receiving long-term procainamide therapy, anti-nuclear antibodies (ANAs) develop, with clinical symptoms occurring in 20% to 30%;this is reversible when procainamide is stopped
60-70%
Causes use-dependent block of I Naand non–use-dependent block of IKr
Muscarinic blocker and can increase the sinus node discharge rate and shorten AV nodal conduction time and refractoriness when the nodes are under cholinergic (vagal) influence
Avoided in patients with reduced left ventricular systolic function
Helps prevent recurrence of AF after successful cardioversion as effectively as quinidine and may terminate atrial flutter.
Disopyramide
Dose: 100 to 300 mg orally every 6 hours, with a range of 400 to 1200 mg/day
Treating patients with AF, particularly atrial flutter, the ventricular rate must be controlled before disopyramide is administered, or the combination of a decrease in atrial rate with vagolytic effects on the AV node can result in 1:1 AV conduction during atrial flutter.
It has been used in patients with hypertrophic cardiomyopathy for both AF therapy and its negative inotropic effect
AE:
MC: Parasympatholytic properties and include urinary hesitancy or retention, constipation, blurred vision, closed-angle glaucoma, and dry mouth.
Produce ventricular arhythmias frequently associated with QT prolongation and TdP.
Disopyramide suppresses _____perforance and is a _____. The drug should generally be avoided in patients with reduced left ventricular systolic function because they tolerate its negative inotropic effects poorly.
Ventricular systolic performance
Mild arterial vasodilator
_____, a rauwolfia derivative, has been used extensively to treat patients with ventricular and supraventricular arrhythmias in Europe and Asia but is not available in the United States.
Ajmaline
When administered intravenously at doses of 50 mg over a 3-minute period, or 10 mg/min, to a total dose of 1 mg/kg, ajmaline can have the following effects:
(1) delta wave disappearance in patients with WPW syndrome (indicating an accessory pathway anterograde ERP longer than 250 milliseconds);
(2) ST-T abnormalities and interventricular conduction block in patients with occult Chagasic cardiomyopathy;
(3) heart block in patients with bundle branch block and syncope, but in whom no rhythm disturbance had been discovered; and
(4) right precordial ST elevation in patients with suspected Brugada syndrome in whom findings on the resting ECG are normal.
Ajmaline can _____ the defibrillation threshold.
Increase
______________ Blocks INa, predominantly in the open or inactivated state. It has rapid onset and offset kinetics and does not affect normal sinus node automaticity in usual doses but does depress other normal and abnormal forms of automaticity, as well as EADs and DADs in Purkinje fibers in vitro
Modest depressant effect on Vmax; however, faster rates of stimulation, acidosis, increased extracellular K + concentration, and reduced membrane potential (changes that can result from ischemia) increase the ability of ___________ to block INa.
Moderate efficacy against ventricular arrhythmias of diverse causes; it is generally ineffective against supraventricular arrhythmias and rarely terminates monomorphic VT.
Lidocaine
Dose: initial bolus of 1 to 2 mg/kg body weight at a rate of 20 to 50 mg/min and a second injection of half the initial dose 20 to 40 minutes later; infusion rates in the range of 1 to 4 mg/min
Clinically significant adverse hemodynamic effects are rarely noted unless with severe LVD
AE: CNS toxicity, d ness, paresthesias, confusion, delirium, stupor, coma, and seizures, dose related; rarely malignant hyperthermia
Lidocaine can convert areas of unidirectional block into bidirectional block during _____ and inhibit the development of _____ by preventing fragmentation of organized large wavefronts into heterogeneous wavelets.
Ischemia
VF
Lidocaine has only a modest depressant effect on Vmax; however,_____ increase the ability of lidocaine to block INa
Faster rates of stimulation
Acidosis
Increased extracellular K+ concentration
Reduced membrane potential (changes that can result from ischemia)
If the initial bolus of lidocaine is ineffective, up to ____.
2 more boluses of 1 mg/kg may be administered at 5-minute intervals
Lidocaine has moderate efficacy against _____ of diverse causes; it is generally ineffective against supraventricular arrhythmias and rarely terminates monomorphic VT.
Ventricular arrhythmias: moderate
SVT: ineffective
Monomorphic VT: rare termination
Although once used in an attempt to prevent VF in the first 2 days after acute MI, its efficacy was marginal, and because it can produce side effects such use is now not recommended.
The most frequently reported adverse effects of lidocaine are dose-related manifestations of _____.
CNS toxicity: dizziness, paresthesias, confusion, delirium, stupor, coma, and seizures
Occasional sinus node depression and His-Purkinje block have been reported.
Rarely, lidocaine can cause malignant hyperthermia.
Local anesthetic congener of lidocaine with anticonvulsant properties, is used for the oral treatment of patients with symptomatic ventricular arrhythmias. It is rarely used as a single agent
Shortens the APD and ERP of Purkinje fibers and, to a lesser extent, ventricular muscle. It depresses the V max of phase 0 by blocking INa , especially at faster rates, and depresses the automaticity of Purkinje fibers
Moderately effective tx in cute and chronic ventricular t rhythmias, but not SVTs; combined with other drugs such as procainamide, beta blockers, quinidine, disopyramide, propafenone, or amiodarone
Mexiletine
Dose: 200 mg orally every 8 hours; inc or dec 50 to 100 mg every 2 to 3 days
Mexiletine exerts no major hemodynamic effects
Mexiletine can result in severe bradycardia and abnormal sinus node recovery time in patients with sinus node disease, but not in those with a normal sinus node. It does not affect AV nodal conduction and can depress His-Purkinje conduction, does not affect the QT interval
In treating patients with a long QT interval, mexiletine may be safer
AE: 40% of patients may require a change in dose or discontinuation of mexiletine therapy as a result of adverse effects, including tremor, dysarthria, dizziness, paresthesia, diplopia
Lidocaine use as an AAD should be avoided in patients receiving mexiletine.
Mexiletine is a moderately effective antiarrhythmic agent for the treatment of acute and chronic ventricular tachyarrhythmias, but not _____. Success rates vary from 6% to 60% and can be increased in some patients if mexiletine is combined with other drugs such as procainamide, beta blockers, quinidine, disopyramide, propafenone, or amiodarone.
SVTs
Phenytoin was used originally to treat seizure disorders. Its value as an AAD is limited to rare cases of _____.
(1) Digitalis-toxic atrial and ventricular tachyarrhythmias (for which more rapid and effective control can be achieved with digitalis-specific antibodies)
(2) occasional cases of ventricular arrhythmias when used in combination with other agents
Exhibits marked use-dependent depressant effects on the rapid sodium channel by decreasing V max and has slow onset and offset kinetics; profoundly slows conduction in all cardiac fibers and, in high concentrations, inhibits the slow Ca2+ channel; Conduction time in the atria, ventricles, AV node, and His-Purkinje system is prolonged.
Can depresses cardiac performance, particularly in patients with compromised ventricular systolic function
Indicated for lifethreatening ventricular tachyarrhythmias, SVTs, and paroxysmal AF, particularly effective in suppressing PVCs and short runs of non-sustained VT, atrial tachycardia (AT), atrial flutter, and AF (including oral loading to terminate episodes acutely)
Can produce ST elevation in lead V1, c acteristic of Brugada syndrome, in susceptible patients and has been used as a diagnostic tool
Flecainide
Dose: 100 mg every 12 hours, increased in increments of 50 mg twice daily, no sooner than every 3 to 4 days,
Increases in serum concentrations of digoxin (15% to 25%) and propranolol (30%)
Flecainide and propafenone may both be used in c tion with beta or calcium channel blockers as a “pill in the pocket”
AE:
Worsening of existing ventricular arrhythmias or the onset of new ventricular arrhythmias can occur in 5% to 30%
Negative inotropic effects can precipitate or worsen heart failure episodes
In CAST, patients treated with flecainide had higher mortality or nonfatal cardiac arrest compared to the placebo group, possibly related to an interaction between the drug and myocardial ischemia. Exercise can amplify the conduction slowing in the ventricle produced by flecainide and in some cases can precipitate a proarrhythmic response. Therefore, exercise testing has been recommended to screen for proarrhythmia (as well as occult ischemia) before and periodically during treatment.
Flecainide _____ cardiac performance, particularly in patients with compromised ventricular systolic function, and should be used cautiously or not at all in those with moderate or severe ventricular systolic dysfunction.
Depresses
Flecainide is indicated for the treatment of _____
Life- threatening ventricular tachyarrhythmias
SVTs
Paroxysmal AF
Proarrhythmic effects are some of the most important adverse effects of flecainide. Its marked slowing of conduction precludes its use in patients with _____ and warrants cautious administration in patients with intraventricular conduction disorders
Second-degree AV block with-out a pacemaker
Exercise can amplify the conduction slowing in the ventricle pro- duced by flecainide and in some cases can precipitate a proarrhythmic response. Therefore, _____ testing has been recommended to screen for proarrhythmia (as well as occult ischemia) before and periodically during treatment.
Exercise testing
_____, represent the most frequent non-cardiac adverse effects of flecainide
CNS complaints, including confusion and irritability
High doses of class IC agents can result in a _____
Markedly prolonged QRS duration
Bundle branch block
Wide and bizarre QRS morphologies during tachycardia
Blocks the fast sodium current in a use-dependent manner in Purkinje fibers and to a lesser degree in ventricular muscle
Treatment of paroxysmal SVT, AF, and life-threatening ventricular tachyarrhythmias, and effectively suppresses spontaneous PVCs and nonsustained and sustained VT. Acute termination of AF episodes occurred with a single 600mg oral dose of propafenone in 76%
Propafenone
Dose: 150 to 300 mg every 8 hours, not to exceed 1200 mg/day (
In patients with left ventricular e tion fraction (EF) exceeding 40%, the negative inotropic effects are well tolerated, but patients with preexisting left ventricular dysfunction and congestive heart failure may exhibit worsening of their symptoms.
Increases the pacing threshold but minimally affects the defibrillation threshold
AE:
Exacerbation of bronchospastic lung disease can occur because of mild beta-blocking effects.
Cardiovascular side effects develop in 10% to 15% of patients - AV block, sinus node depression, and worsening of heart failure
Beta Blocking Agents - Class II
Metoprolol, carvedilol, atenolol, propranolol, and esmolol have been most widely used to treat supraventricular and ventricular arrhythmias
In low doses, ___________________ can block β1 receptors more than they block β2 receptors and might be preferable for the treatment of patients with pulmonary or peripheral vascular disease. In high doses, the “selective” β 1 blockers also block β 2 receptors.
________________ also exerts alpha-blocking effects and is used primarily in patients with heart failure
___________ induce less depression of left ventricular function than do beta blockers without intrinsic sympathomimetic activity.
Selective beta blockers
Carvedilol
Beta blockers with intrinsic sympathomimetic
Arrhythmias associated with thyrotoxicosis or pheochromocytoma and arrhythmias largely related to excessive cardiac adrenergic stimulation, such as those initiated by exercise or emotion
Beta-blocking drugs do not usually convert chronic atrial flutter or AF to normal sinus rhythm
Beta blockers exert negative inotropic effects and can precipitate or worsen heart failure. However, beta blockers clearly improve survival in patients with heart failure
_____ decrease overall mortality and sudden death after MI
Propranolol
Atenolol
Carvedilol
Timolol
Metoprolol
Adverse cardiovascular effects from beta blockers include unacceptable _____.
Hypotension
Bradycardia
Congestive heart failure
Indications for using Beta blockers
(1) Arrhythmias associated with thyrotoxicosis or pheochromocytoma and arrhythmias largely related to excessive cardiac adrenergic stimulation
(2) AF of recent onset and in patients who have recently undergone cardiac surgery
(3) Reentrant SVTs using the AV node as one of the reentrant pathways, such as AV nodal reentrant tachycardia (AVNRT) and orthodromic reciprocating tachycardia in WPW syndrome or inappropriate sinus tachycardia, or for AT, beta blockers can slow or terminate the tachycardia and can be used prophylactically to prevent a recurrence
(4) Digitalis-induced arrhythmias such as AT, nonparoxysmal AV junctional tachycardia, PVCs, or VT
(5) Ventricular arrhythmias associated with prolonged–QT interval syndrome and MVP
Sudden withdrawal of _____ in patients with angina pectoris can precipitate or worsen angina and cardiac arrhythmias and cause acute MI, possibly as a result of the heightened sensitivity to beta agonists caused by previous beta blockade (receptor upregulation). Heightened sensitivity may begin several days after cessation of beta-blocker therapy and can last _____ days
Propranolol
5-6 days
Other adverse effects of beta blockers include _____.
Worsening of asthma or COPD
Intermittent claudication
Raynaud phenomenon
Mental depression
Increased risk for hypoglycemia in insulindependent diabetic patients
Easy fatigability
Dsturbingly vivid dreams or insomnia
Impaired sexual function
___________________ is an iodinated benzofuran derivative approved by the FDA for the treatment of patients with life-threatening ventricular tachyarrhythmias when other drugs are ineffective or not tolerated.
This drug and its metabolite ________________ prolong the APD of ventricular muscle but shorten the APD of Purkinje fibers. It depresses Vmax in ventricular muscle in a rate- or use-dependent manner by blocking inactivated sodium channels. The ERP of all cardiac tissues is prolonged. The H-V interval increases, and the QRS duration lengthens, especially at fast rates
This has class I (blocks INa ), class II (antiadrenergic), and class IV (blocks ICa.L ) actions in addition to its class III effects (blocks IK)
Amiodarone
Desethylamiodarone
Decreases the heart rate, systemic vascular resistance, and left ventricular dP/dt when administered IV
Dose: 800 to 1200 mg/day for 1 to 3 weeks, 400 to 800 mg/day for 1 to 2 weeks, and finally after 2 to 3 months of treatment, a maintenance dose of 200 mg per day
To achieve more rapid loading and effect in emergencies, amiodarone can be administered intravenously at initial doses of 15 mg/min for 10 minutes, followed by 1 mg/min for 6 hours and then 0.5 mg/min for the remaining 18 hours and the next several days as necessary
The efficacy of amiodarone equals or exceeds that of all other AADs and may be in the range of 60% to 80% for most supraventricular tachyarrhythmias and 40% to 60% for ventricular tachyarrhythmias
Amiodarone has been shown to result in inferior survival compared with ICD therapy, and in the SCD-HeFT population (New York Heart Association [NYHA] class II or III heart failure; EF, 35%), survival of amiodarone-treated patients was no different than for the placebo group. The drug may still be used adjunctively in ICDtreated patients to decrease the frequency of shocks from VT and VF episodes or to control supraventricular tachyarrhythmias that elicit device therapy
Effects of Amiodarone
Long term administration:
amiodarone prolongs the APD and refractoriness of all cardiac fibers without affecting resting membrane potential
Acute:
Desethylamiodarone prolong the APD of ventricular muscle but shorten the APD of Purkinje fibers
_____
Depresses V”max in ventricular muscle in a rate- or use-dependent manner by blocking inactivated sodium channels
Noncompetitively antagonizes alpha and beta receptors and blocks conversion of thyroxine (T4) to triiodothyronine (T3)
Exhibits slow channel–blocking effects; with oral administration, it slows the sinus rate by 20% to 30% and prolongs the QT interval, at times changing the contour of the T wave and producing U waves
Amiodarone is a peripheral and coronary vasodilator. When administered intravenously (150 mg over 10 minutes, then a 1-mg/min infusion), amiodarone _____.
Decreases:
HR
SVR
Left ventricular dP/dt
Dosing of amiodarone
There is no standard dosng schedule for amiodarone applicable to all patients.
One recommended approach is to treat with:
800 to 1200 mg/day for 1 to 3 weeks,
400 to 800 mg/day for 1 to 2 weeks,
and finally after 2 to 3 months of treatment,
a maintenance dose of 200 mg per day
To achieve more rapid loading and effect in emergencies, amiodarone can be administered intravenously at initial doses of _____ and the next several days as necessary.
15 mg/min for 10 minutes
followed by 1 mg/min for 6 hours
and then 0.5 mg/min for the remaining 18 hours
Supple- mental infusions of 150 mg over a 10-minute period can be used for breakthrough VT or VF. Intravenous infusions can be continued safely for _____ weeks.
2-3 weeks
Patients with depressed EF should receive IV amiodarone with great caution because of hypotension. High-dose oral loading (_____)may suppress ventricular arrhythmias in _____ days.
800 to 2000 mg/day to maintain trough serum concentrations of 2 to 3 μg/mL
5-7 days
However, amiodarone has been shown to result in inferior survival compared with ICD therapy, and in the SCD-HeFT population (New York Heart Association [NYHA] class II or III heart failure; EF, 35%), survival of amiodarone-treated patients was _____t than for the placebo group
No different
Adverse effects are reported by about 75% of patients treated with amiodarone for 5 years, and these effects compel stopping the drug in 18% to 37%. The most frequent side effects requiring drug discontinuation involve _____complaints or abnormal test results. Most adverse effects are reversible with dose reduction or cessation of treatment. .Adverse effects are more common when therapy is continued in the long term and at higher doses
Pulmonary and GI
Of the non-cardiac adverse reactions of amiodarone, _____ toxicity is the most serious; in one study, it occurred in 33 of 573 patients between 6 days and 60 months of treatment, with three deaths. The mechanism is unclear but may involve a _____.
Pulmonary toxicity
Hypersensitivity reaction, widespread phospholipidosis, or both
_____ are the most common symptoms of amiodarone-induced pulmonary toxicity, along with_____ on examination, _____.
Dyspnea and nonproductive cough
Fine crackles
Hypoxia
Abnormal gallium scan results,
Reduced carbon monoxide diffusion capacity (DLCO)
Radiographic evidence of pulmonary infiltrates
Because amiodarone appears to inhibit the peripheral conversion of T4 to T3, chemical changes result and are characterized by a slight increase in _____ and a slight decrease in ___ levels.The reverse T3 concentration has been used as an index of drug effect.
Slight increase in:
T4
reverse T3 - used as an index of drug effect
TSH
Slight decrease in:
T3
In amiodarone-induced thyroid disease, during hypothyroidism the ___ level increases greatly, whereas the level of __ increases in hyperthyroidism.
Hypothyroidism: TSH
Hyperthyroidism: T3
Thyroid function tests should be performed approximately every ____ months for the first year while amiodarone is being taken and _____ yearly thereafter, or sooner if symptoms develop that are consistent with thyroid dysfunction
1st year: every 3 months
Thereafter: 1-2x yearly
Corneal microdeposits occur in almost 100% of adults receiving the drug longer than _____ months. More serious ocular reactions, including optic neuritis and atrophy with visual loss, have been reported but are rare, and causation by amiodarone has not been firmly established
> 6 months
Among the most common side effects limiting long-term drug use are _____, and these side effects are both dose and duration related as well as idiosyncratic. Lowering the dose of amiodarone frequently decreases the severity of the side effect.A wide variety of neurologic toxicities have been described including tremor, ataxia, peripheral neuropathy, and rarely myopathy and encephalopathy.
Neurologic
Cardiac side effects of Amiodarone include _____. Despite QT prolongation, amiodarone causes TdP rarely presumably due to the inhibition of multiple K channels and L-type Ca channels
(1) Symptomatic bradycardias in approximately 2% of patients;
(2) Rare development of TdP in 1% to 2%
Recommended Follow-up for Amiodarone
(1) ECG at routine clinic follow ups, and at least every 12 months
(2) Liver function tests at baseline and every 6 months or if patient presents with clinical features of liver disease
(3) Thyroid function test (thyroid stimulating hormone) at baseline and every 4–6 months or if patient presents with clinical features suggestive of thyroid disease
(4) Chest radiography at baseline and every year or for new and changing symptoms
(5) Pulmonary function tests at baseline (including DLCO) and if symptoms develop, especially in patients with underlying lung disease or abnormalities on chest radiography
(6) Skin examination at routine follow-up every 6–12 months
Neurologic examination at routine follow-up. Note side effects are dose- and duration-related. Reduced dose should ameliorate symptoms.
(7) Ophthalmologic examination at baseline if there is visual impairment and yearly or for any change in vision
(8) Be aware of numerous drug interactions and drugs contraindicated with concomitant use of amiodarone, especially drugs that prolong QT interval or interact with amiodarone metabolism
Important interactions with other drugs occur, and when given concomitantly with amiodarone, the doses of _____ should be reduced by one third to one half and the patient observed closely
Warfarin
Digoxin
Other AADs
The safety of amiodarone during pregnancy is controversial but categorized currently as class _____. It should be used in pregnant patients only if no alternatives exist but should be avoided during breastfeeding.
Class D
The most serious adverse effect/toxicity of amiodarone?
Pulmonary toxicity
At maintenance doses lower than 200 mg/day, pulmonary toxicity is uncommon but can still occur
Other AE:
Elevations in LFT (Amiodarone is not stopped unless values exceed two or three times the upper limit of normal in a patient with initially normal values)
Neurologic dysfunction, photosensitivity (perhaps minimized by sunscreens), bluish skin discoloration, GI disturbances, and hyperthyroidism (1% to 2%) or hypothyroidism (2% to 4%)
Because amiodarone appears to inhibit the peripheral conversion of T 4 to T3 , chemical changes result and are characterized by a slight increase in T4 , reverse T3 , and thyroid-stimulating hormone (TSH) and a slight decrease in T3 levels (TFTs every 3 months)
Despite QT prolongation, amiodarone causes TdP rarely presumably due to the inhibition of multiple K channels and L-type Ca channels.
_____________approved by the FDA to facilitate maintenance of sinus rhythm in patients with atrial flutter and AF
It is a more potent blocker of I Na than amiodarone and exhibits similar effects on the L-type calcium current.
Should not be used in those with clinical signs of heart failure
Indicated to facilitate cardioversion of atrial flutter or AF or to maintain sinus rhythm after restoration of sinus rhythm.
Dronedarone
Dose: 400 mg every 12 hours
Identify the trial
Patients received either 400 mg twice daily of dronedarone or matching placebo
The results indicate that the use of dronedarone in patients with heart failure, especially those with systolic dysfunction, is associated with a higher incidence of mortality compared with placebo, primarily from death due to CHF and arrhythmias. There also seems to be a higher incidence of increase in serum creatinine with treatment with dronedarone, although whether this resulted in renal failure or other consequences is unknown.
ANDROMEDA (Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease)
Dronedarone-treated patients had a mortality rate more than twice that of the placebo group (8.1% vs. 3.8%)
Identify the trial
Patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo
Results showed increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients
PALLAS (Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy)
Patients with permanent AF who were taking dronedarone had a greater than twofold higher risk for death, stroke, systemic embolism, or MI than did control patients. Thus, the medication should not be used in patients with current or recent episodes of clinical heart failure or those with permanent AF (as a rate control agent).
Subsets of patients that Dronedarone should not be used?
Severe liver dysfunction
Heart Failure - class III or IV
Permanent AF
Pregnancy (Category X)
______________ is a nonspecific beta adrenoceptor blocker without intrinsic sympathomimetic activity that prolongs repolarization. It is approved by the FDA to treat patients with life-threatening ventricular tachyarrhythmias and those with AF
Does not block alpha adrenoceptors and does not block I Na (no membranestabilizing effects) but does prolong atrial and ventricular repolarization times by reducing IKr , thus prolonging the plateau of the action potential. A
Sotalol
It must be used cautiously in patients with marginal cardiac compensation but is well tolerated in those with normal cardiac function
Dose: 80 to 160 mg every 12 hours, with 2 to 3 days between dose adjustments
Approved by the FDA to treat patients with ventricular tachyarrhythmias and AF, sotalol is also useful to prevent recurrence of a wide variety of SVTs, including atrial flutter, AT, AV node reentry, and AV reentry
Sotalol has been used successfully to decrease the incidence of AF after cardiac surgery.
_________________ is the most serious adverse effect of Sotalol
Proarrhythmia
Overall, new or worsened ventricular tachyarrhythmias occur in approximately 4% of patients taking sotalol; this response is the result of TdP in approximately 2.5% but increases to 4% in patients with a history of sustained VT and is dose related (only 1.6% at 320 mg/day but 4.4% at 480 mg/day). This proarrhythmic effect was probably the cause of excess mortality in patients given d-sotalol (the enantiomer lacking a beta-blocking effect) after acute MI in the SWORD (Survival With Oral d-Sotalol) trial.
________________ is an agent released for acute termination of episodes of atrial flutter and AF, also blocks accessory pathway conduction
Indicated for termination of an e lished episode of atrial flutter or AF
It should not be used in patients with frequent short paroxysms of AF because it merely terminates episodes and is not useful for long-term prevention.
Ibutilide
Dose: given as an IV 1 mg over 10 minutes
Should NOT be given in the presence of a QTc interval longer than 440 milliseconds or other drugs that prolong the QT interval or in patients with uncorrected hypokalemia, hypomagnesemia, or bradycardia
Patients must have c tinuous electrocardiographic monitoring throughout the dosing period and for up to 4 hours thereafter because of the risk for ventricular arrhythmias. Pretreatment with IV magnesium may decrease the risk for ventricular arrhythmias and enhance efficacy in treating some atrial arrhythmias. Up to 60% of patients with AF and 70% of those with atrial flutter convert to sinus rhythm after 2 mg of ibutilide has been administered.
Ibutilide has been administered at transthoracic electrical cardioversion to increase the likelihood of termination
Ibutilide prolongs accessory pathway refractoriness and can temporarily slow the ventricular rate during preexcited AF. The drug can rarely terminate episodes of organized AT, as well as sustained, uniformmorphology VT.
Pretreatment with _____ with Ibutilide use may decrease the risk for ventricular arrhythmias and enhance efficacy in treating some atrial arrhythmias.
IV magnesium
Up to 60% of patients with AF and 70% of those with atrial flutter convert to sinus rhythm after __ mg of ibutilide has been administered.
2 mg
The most significant adverse effect of ibutilide is ___________________
QT prolongation–related TdP
This effect develops within the first 4 hours of dosing or until the QTc has returned to baseline, after which the risk is negligible. Thus, patients must undergo electrocardiographic monitoring for up to 4 hours after dosing (or longer, until QTc returns to baseline)
___________________ is approved for the acute conversion of AF to sinus rhythm, as well as for chronic suppression of recurrent AF
Sole electrophysiologic effect is block of the rapid component of the delayed rectifier potassium current (IKr)
Indicated for prevention of e sodes of supraventricular tachyarrhythmias, particularly atrial flutter and fibrillation.
It has no significant hemodynamic effects, is more effective than quinidine at converting AF to sinus rhythm
Dofetilide
Dose: 0.125 to 0.5 mg twice daily and must be initiated in a hospital setting with continuous electrocardiographic monitoring to ensure that excessive QT prolongation and TdP do not develop
Should NOT be given to patients with a creatinine clearance lower than 20 mL/min or a baseline QTc interval longer than 440 milliseconds
The sole electrophysiologic effect of dofetilide is block of the rapid component of the ____, important in repolarization
Delayed rectifier potassium current (IKr)
The most significant adverse effect of dofetilide is _______________
QT interval prolongation–related TdP
Risk is highest in patients with a baseline prolonged QT interval, in those who are hypokalemic, in those taking some other agent that prolongs repolarization, and after conversion from AF to sinus rhythm. Because the risk for TdP is highest at drug initiation, it should be used continuously and not as intermittent outpatient dosing. The drug is otherwise well tolerated, with few side effects.
_________________, a synthetic papaverine derivative, is the prototype of a class of drugs that block the slow calcium channel and reduce I Ca.L in cardiac muscle
Similar with?
Verapamil
Diltiazem
_________________ inhibits vascular smooth muscle contraction and causes marked vasodilation in coronary and other peripheral vascular beds.
The reflex sympathetic effects of verapamil may reduce its marked negative inotropic action on isolated cardiac muscle
IV verapamil or diltiazem is the next treatment of choice for termination of sustained AV node reentry or orthodromic AV reciprocating tachycardia associated with an accessory pathway after Adenosine
Verapamil/Diltiazem
Dose: For acute termination of SVT or rapid achievement of ventricular rate control during AF, the most common IV dose of verapamil is up to 10 mg infused over 1 to 2 minutes; the initial effect achieved with the first bolus injection, such as slowing of the ventricular response during AF, can be maintained by continuous infusion of the drug at a rate of 0.005 mg/kg/min. The oral dose is 240 to 480 mg/day in divided doses
In patients with preexcited ventricular complexes during AF associated with WPW syndrome, IV verapamil may accelerate the ventricular response; therefore, the IV route is contraindicated in this situation
Even though verapamil can often terminate an idiopathic left septal VT, hemodynamic collapse can occur if IV verapamil is given to patients with the more common forms of VT because these generally occur in the setting of decreased left ventricular systolic function. A general rule for avoiding complications, however, is not to administer verapamil intravenously to any patient with wide-QRS tachycardia unless one is certain of the nature of the tachycardia and its probable response to verapamil.
By blocking ICa.L in all cardiac fibers, verapamil _____.
Reduces the plateau height of the action potential
Slightly shortens muscle action potential at pharmacologic concentrations
Slightly prolongs Purkinje fiber action potential
Dosage and administration of Verpamil
For acute termination of SVT or rapid achievement of ventricular rate control during AF, the most common IV dose of verapamil is up to _____ while cardiac rhythm and blood pressure are monitored.A second injection of an equal dose may be given 30 minutes later. The initial effect achieved with the first bolus injection, such as slowing of the ventricular response during AF, can be maintained by continuous infusion of the drug at a rate of _____.The oral dose is ____ in divided doses
Bolus: 10 mg infused over 1 to 2 minutes
Infusion: 0.005 mg/kg/min
Oral: 240 to 480 mg/day
Diltiazem is given intravenously at a dose of _____ as a bolus over 2 minutes, with a second dose in 15 minutes if necessary. Because it is generally better tolerated (less hypotension) with long-term administration, such as for control of the ventricular rate during AF, diltiazem is preferred over verapamil in this setting. Significant hypotension resulting from IV diltiazem can be countered by volume expansion or judicious use of a pure vasoconstrictor agent such as phenylephrine. Orally, doses must be adjusted to the patient’s needs, with a _____ range
IV: 0.25 mg/kg over 2 mins, 2nd dose in 15 mins
Oral: 120- to 360-mg
As noted earlier, in patients with _____ during AF associated with WPW syndrome, IV verapamil may accelerate the ventricular response; therefore, the IV route is contraindicated in this situation
Preexcited ventricular complexes
.Verapamil has not generally been effective in treat- ing patients who have recurrent ventricular tachyarrhythmias, although it may suppress some forms of VT, such as _____
Left septal VT
Verapamil should also be used with caution in patients with sinus node abnormalities because marked depression of sinus node function or asystole can result in some of these patients. IV _____, which may be only partially effective, or temporary pacing may be necessary to counteract some of the adverse effects of verapamil.
Calcium glucagon
Isoproterenol
Dopamine
Atropine
_____ may be more effective for the treatment of bradyarrhythmias, and _____ may be used for the treatment of hemodynamic dysfunction secondary to verapamil
Brady: Isoproterenol
hemodynamic dysfunction: Calcium
Contraindications to the use of verapamil and diltiazem include the presence of _____.
Advanced heart failure
2nd or 3rd degree AV block without a pacemaker in place
AF and anterograde conduction over an accessory pathway
Significant sinus node dysfunction
Most VTs
Cardiogenic shock and other hypotensive states
_______________ interacts with G-protein coupled A 1receptors present on the extracellular surface of cardiac cells and activates K +channel; shortens the atrial APD, hyperpolarizes the membrane potential, and decreases atrial contractility. Similar changes occur in the sinus and AV nodes
Drug of first choice to terminate an SVT acutely, such as AV node or AV reentry
This slows the sinus rate in humans, followed within seconds by a reflex increase in the sinus rate. In the AV node, adenosine produces transient prolongation of the A-H interval, often with transient first-, second-, or third-degree AV node block
Does not affect conduction in normal accessory pathways
Adenosine
Dose: 6 to 12 mg, followed by a flush; When it is injected into a central vein and in patients after heart transplantation or those receiving dipyridamole, the initial dose should be reduced to 3 mg; doses higher than 18 mg are unlikely to revert a tachycardia and should not be used
It results in only transient AV block during atrial flutter or fibrillation and is thus useful only for diagnosis, not therapy
Adenosine may be useful to help differentiate among causes of wide-QRS tachycardias because it terminates many SVTs with aberrancy or reveals the underlying atrial mechanism and does not block conduction over an accessory pathway or terminate most VT
This agent may predispose to the development of AF and might transiently increase the ventricular response in patients with AF conducting over an accessory pathway.
Electrophysiologic effects of adenosine
Increase in K+ conductance:
Shortens the atrial APD
Hyperpolarizes the membrane potential
Decreases atrial contractility
Adenosine slows the sinus rate in humans, followed within seconds by a reflex increase in the sinus rate. In the AV node, adenosine produces transient prolongation of the A-H interval, often with transient first-, second-, or third-degree AV node block lasting up to a few seconds.
Conduction may be blocked in unusual accessory pathways that have long conduction times or decremental conduction properties
The vascular endothelium and erythrocytes contain these elimination systems, which result in very rapid clearance of adenosine from the circulation. Its elimination half-life is _____ seconds
1-6s
_____ has become the drug of first choice to terminate an SVT acutely, such as AV node or AV reentry, and is useful in pediatric patients
Adenosine
To terminate tachycardia, a bolus of adenosine is rapidly injected intravenously at doses of _____. Transient sinus slowing or AV node block results but lasts less than _____ seconds. Doses higher than 18 mg are unlikely to revert a tachycardia and should not be used.
6 to 12 mg, followed by a flush
<5s
Adenosine terminates a group of VTs whose maintenance depends on adrenergic drive, which is most often located in the _____ but can be found at other sites as well; however, idiopathic left septal VT rarely responds.
RVOT VT
Transient side effects occur in almost 40% of patients with SVT given adenosine and usually consist of _____________________. These symptoms are fleeting, lasting less than 1 minute, and are well tolerated.
Flushing, dyspnea, and chest pressure
Doses as low as ___ mg terminate some tachycardias; doses of 12 mg or less terminate 92% of SVTs, usually within 30 seconds.
Some tachycardias: 2.5 mg
SVT: </= 12 mg
_____ might be chosen first in patients receiving drugs such as theophylline (which is known to interfere with adenosine’s actions or metabolism), in patients with active broncho- constriction, and in those with inadequate venous access.
Verapamil
This agent may predispose to the development of AF and might transiently increase the ventricular response in patients with AF conducting over an accessory pathway.
AF is occasionally observed (12% in one study) with adenos- ine administration, perhaps because of the drug’s effect in shortening atrial refractoriness
Adenosine
_________________ acts mainly through the autonomic nervous system, in particular by enhancing both central and peripheral vagal tone; slowing of the sinus node discharge rate, shortening of atrial refractoriness, and prolongation of AV nodal refractoriness
Used to slow the ventricular rate during AF and atrial flutter; more often used orally to control the ventricular rate in permanent (“chronic”) AF
Digoxin
Dose: In acute loading doses of 0.5 to 1.0 mg, digoxin can be given orally or intravenously; 0.125 to 0.25 mg/day as a single dose; renal adjustment
When a patient with AF is at rest and vagal tone p dominates, the ventricular rate can be maintained between 60 and 100 beats/min in 40% to 60% of cases. However, when the patient begins to exercise, the decrease in vagal tone and increase in adrenergic tone combine to diminish the beneficial effects of digoxin on AV nodal conduction
Digoxin is therefore rarely used as a single agent to control the ventricular rate in AF. The drug has little ability to prevent episodes of paroxysmal AF or to control the ventricular rate during episodes and may even provoke episodes in patients with so-called vagal AF. Furthermore, digoxin is not more effective than placebo in terminating episodes of acute- or recent-onset AF.
Electrophysiologic actions of Digoxin
- Acts mainly through the autonomic nervous system, in particular by enhancing both central and peripheral vagal tone.
- Confined largely to:
Slowing of the sinus node discharge rate
Shortening of atrial refractoriness
Prolongation of AV nodal refractoriness)
The sinus rate may decrease in patients with heart failure whose left ventricular performance is improved by the drug;
The characteristic ST and T wave abnormalities seen with use of digoxin do not represent toxicity.
Serum half life of Digoxin
36-48 hrs (excreted in the kidneys)
Acute loading dose of Digoxin
In acute loading doses of 0.5 to 1.0 mg, digoxin can be given orally or intravenously
Chronic daily oral dosing of Digoxin
Most patients: 0.125 to 0.25 mg/day as a single dose
Some patients undergoing renal dialysis need as little as 0.125 mg every other day, whereas young patients may require as much as 0.5 mg/day
Indications for using Digoxin
- IV to slow the ventricular rate during AF and atrial flutter (formerly used in an attempt to convert SVTs to sinus rhythm,but its onset of action is much slower and its success rate less than that of adenosine, verapamil, or beta blockers)
- often used orally to control the ventricular rate in permanent (“chronic”) AF. When a patient with AF is at rest and vagal tone predominates, the ventricular rate can be maintained between 60 and 100 beats/min in 40% to 60% of cases.
- The drug has little ability to prevent episodes of paroxysmal AF or to control the ventricular rate during episodes and may even provoke episodes in patients with so-called vagal AF.
Digitalis toxicity
Digitalis toxicity - headache, nausea and vomiting, altered color perception, halo vision, and generalized malaise
Less common but more serious than these are ______, which include bradycardias related to a greatly enhanced vagal effect (e.g., sinus bradycardia or arrest, AV node block) and tachyarrhythmias that may be caused by DAD-mediated triggered activity (e.g., junctional, and fascicular or VT).
Digitalis-related arrhythmias
______ increase a patient’s sensitivity to digitalis-related arrhythmias.
Worsening renal function
Advanced age
Amyloidosis
Chronic lung disease
Hypothyroidism
Hypokalemia
Therapy for digitalis toxicity
Bradycardia - withdrawal, atropine, temporary pacing in symptomatic patients
Atrial tachyarrhythmias - Phenytoin
Infranodal taachycardias - Lidocaine
Life-threatening arrhythmias - Digoxin-specific Ab fragments, VT - Electrical DC cardioversion
_________________ produces various symptoms and signs, increasing headache, nausea and vomiting, altered color perception, halo vision, and generalized malaise
Digital toxicity
Worsening renal function, advanced age, hypokalemia, chronic lung disease, hypothyroidism, and amyloidosis increase a patient’s sensitivity to digitalis-related arrhythmias
_________________ approved for treatment of chronic angina, has significant electrophysiologic properties. It has been shown to decrease the incidence of AF, SVT, and ventricular arrhythmias relative to controls in trials of the drug’s antianginal effects
Blocks IKr, as well as the late Na current; at higher c tions, the L-type Ca current is mildly affected; prolongs atrial and ventricular r ness and induces postrepolarization refractoriness
Has no important hemodynamic effects
Ranolazine
Dose: 500 mg twice daily, to a maximum of 1000 mg twice daily
The most widely known potential adverse effect of ranolazine is QTc prolongation, which averages 6 to 15 milliseconds (sometimes more in patients with severe liver failure), because of inhibition of IKr . Despite this effect on the QT interval, TdP is rare, probably in part because of only modest QT prolongation combined with the drug’s inhibition of the late inward Na current, which mitigates the QT effect.
Electrophysiologic actions of Ranolazine
(1) Blocks IKr, as well as the late Na current; at higher concentrations, the L-type Ca current is mildly affected
(2) Prolongs atrial and ventricular refractoriness and induces postrepolarization refractoriness; the P wave, PR inter-val, and QRS are unaffected, but the QT interval is mildly prolonged.
Unlike other IKr-blocking drugs, ranolazine does not induce EADs. Its effects are more pronounced on atrial than on ventricular myocardium, and the drug shows promise for the treatment of AF, particularly when combined with dronedarone
Hemodynamic effects of Ranolazine
None
Dosing of Rano;azine
The typical oral dose of ranolazine is 500 mg twice daily, to a maximum of 1000 mg twice daily.
The most widely known potential adverse effect of ranolazine is ______, which averages _____ (sometimes more in patients with severe liver failure), because of inhibition of IKr. Despite this effect on the QT interval, TdP is rare, probably in part because of only modest QT prolongation combined with the drug’s inhibition of the late inward Na current, which mitigates the QT effect.
QTc prolongation 6-15 ms
________________ approved by the FDA for reducing the risk of h ization for worsening heart failure in patients with stable, symptomatic heart failure and a reduced EF in sinus rhythm with a resting heart rate ≥70 beats/min and taking maximally tolerated doses of beta blockers; has been used to treat inappropriate sinus tachycardia
Blocks the pacemaker or “funny” current (If), the current responsible for generating spontaneous depolarization in the sinus node; funny current is a mixed Na+-K +inward current activated by hyperpolarization
No hemodynamic effects or alterations of cardiac contractility
Ivabradine
Dose: started at a dose of 5 mg twice per day (2.5 mg bid if the resting heart rate is <60 beats/min) and may be increased to 7.5 mg twice daily
The most common non-cardiac side effect is visual disturbances, specifically transient flashes of brightness in the visual field.
Ivabradine is approved by the FDA for reducing the risk of hospitalization for worsening heart failure in patients with stable, symptomatic heart failure and a reduced EF in sinus rhythm with a resting heart rate ___ beats/min and taking maximally tolerated doses of beta blockers. Ivabradine has been used to treat inappropriate sinus tachycardia.
70 bpm
Electrophysiologic actions of Ivabradine
Ivabradine blocks the pacemaker or “funny” current (If), the current responsible for generating spontaneous depolarization in the sinus node
Dosing of Ivabradine
Started at a dose of 5 mg twice per day (2.5 mg bid if the resting heart rate is <60 beats/min)
May be increased to 7.5 mg twice daily to increase its effects.
The dosage may be lowered if excessive bradycardia is encountered.The dose is typically titrated after 2 weeks.
The most common non-cardiac side effect is _____.When ivabradine is used in combination with other QT prolonging drugs it may increase the risk of _____.
Visual disturbances, specifically transient flashes of brightness in the visual field
TdP
Several medications commonly used for other indications also have some degree of antiarrhythmic effect. In some cases, physicians can use these drugs for their standard indications and achieve additional, although often small, amounts of benefit in treating the patient’s rhythm disturbance. These drugs include:
ACEi and ARBs
Aldosterone antagonists such as eplerenone
Statins
Omega-3 fatty acids (prevention of sudden death)
Non-dihydropyridine CCBs and ranolazine (less AF and perhaps VF)
_______________ general term used to indicate the termination of an arrhythmia, usually a tachyarrhythmia, by various means, including electrical, pharmacologic, or manual/surgical.
Cardioversion
_______________ refers to the delivery of an electrical shock to the heart to terminate a tachycardia, flutter, or fibrillation and includes the technique of both synchronous cardioversion and defibrillation.
Electrical cardioversion
offers obvious advantages over drug therapy because under conditions optimal for close supervision and monitoring, a precisely regulated “dose” of electricity can restore sinus rhythm immediately and safely
_____________ most effective in terminating tachycardias related to reentry, such as atrial flutter and many cases of AF, AV node reentry, reciprocating tachycardias associated with WPW syndrome, most forms of VT, ventricular flutter, and VF.
Electrical Cardioversion
The electrical shock, by depolarizing all excitable myocardium and possibly by prolonging refractoriness, interrupts reentrant circuits and establishes electrical homogeneity, which terminates reentry.
_________________ refers to a specific technique of delivering an electrical shock, usually of lower energy and timed to the QRS complex (“R wave”), to avoid the vulnerable period of the T wave.
Synchronous cardioversion
Administration of maintenance AADs 1 to 2 days before planned electrical cardioversion of patients with AF can revert some patients to sinus rhythm, help prevent recurrence of AF once sinus rhythm is restored, and assist in determining the patient’s tolerance of the drug for long-term use
Patches 12 to 13 cm in diameter can be used to deliver maximum current to the heart
Except for AF, shocks in the range of 25 to 50 joules (J) successfully terminate most SVTs and should be tried initially
The starting level to terminate AF with older monophasic machines should be no less than 100 J, but with newer biphasic systems, a shock as low as 25 J may succeed
A posterior patches may have a higher efficacy rate by placing more of the atrial mass in the shock vector than is the case with apicoanterior patches. I
A _____ shock (i.e., one delivered during the QRS complex) is used for all cardioversions except for very rapid ventricular tachyarrhythmias, such as ventricular flutter or VF.
Synchronized
For defibrillation of the ventricular flutter or fibrillation, energies greater than those for synchronous cardioversion are required, and synchronization is not necessary because there is _____.
No vulnerable period of the T wave to avoid
Except for AF, shocks in the range of _____ joules (J) successfully terminate most SVTs and should be tried initially.If the shock is unsuc- cessful,a second shock of higher energy can be delivered.
25 to 50 J
The starting level to terminate AF with older monophasic machines should be no less than _____ J, but with newer biphasic systems, a shock as low as _____ J may succeed.
Monophasic: 100 J
Biphasic: 25 J
Antero- posterior patches may have a higher efficacy rate by placing more of the atrial mass in the shock vector than is the case with apicoanterior patches
Antero-posterior
For patients with stable VT, starting levels in the range of _____ J can be used
25-50 J
To terminate VF, a _____ is generally used, although much lower energies (<___ J) terminate VF when the shock is delivered soon after onset of the arrhythmia, for example, using previously placed adhesive patches in the electrophysiology laboratory.
Biphasic 100 to 200 J (200 to 360 J with monophasic)
<50 J
Administration of __________ has been shown to facilitate electrical cardioversion of AF to sinus rhythm
Ibutilide
In up to __% of patients with AF, sinus rhythm cannot be restored by external countershock despite all the preceding measures, including ibutilide pretreatment and biphasic shocks
5%
Patients in whom AF simply cannot be terminated with an external shock tend to be very obese or have severe obstructive lung disease.In such patients, internal cardioversion can be performed with the use of specially configured catheters that have multiple large electrodes covering several centimeters of the distal portion of the catheter for distributing the shock energy. Internal shocks of _____ J can terminate AF in more than 90% of patients whose arrhythmia was refractory to transthoracic shock.
2 to 15 J
As a general rule, any non-sinus tachycardia that produces _____ should be terminated electrically.
Hypotension
Congestive heart failure
Mental status changes
Angina and does not respond promptly to medical management
Favorable candidates for electrical cardioversion of AF include patients who _____.
(1) have symptomatic AF of less than 12 months’ duration
(2) continue to have AF after the precipitating cause has been removed (e.g., after treatment of thyrotoxicosis)
(3) have a rapid ven- tricular rate that is difficult to slow,or
(4) have symptoms of decreased cardiac output (e.g., fatigue, lightheadedness, dyspnea) attributable to lack of atrial contraction’s contribution to ventricular filling
It is important to distinguish between inability to attain sinus rhythm, indicating failure of the shock to convert the arrhythmia, and inability to maintain sinus rhythm after transient termination of fibrillation
The latter condition (early re-initiation of AF) does not respond to higher-energy shocks because fibrillation has already been terminated but quickly recurs.
Pretreatment with an _________ may help maintain sinus rhythm after subsequent shocks.
AAD
Any non-sinus tachycardia that produces ______________, _____________, ________________, ________________ and does not respond promptly to medical management should be terminated electrically.
Hypotension, ongestive heart failure, mental status changes, or angina
Very rapid ventricular rates in patients with AF and WPW s drome are often best treated by electrical cardioversion.
Favorable candidates for electrical cardioversion of AF include patients who
(1) have symptomatic AF of less than ______________ duration
(2) continue to have AF after the precipitating cause has been removed (e.g., after treatment of thyrotoxicosis)
(3) have a rapid ventricular rate that is difficult to slow
(4) have symptoms of decreased cardiac output (e.g., fatigue, lightheadedness, dyspnea) attributable to lack of atrial contraction’s contribution to ventricular filling
(1) have symptomatic AF of less than 12 months’ duration
(2) continue to have AF after the precipitating cause has been removed (e.g., after treatment of thyrotoxicosis
(3) have a rapid ventricular rate that is difficult to slow
(4) have symptoms of decreased cardiac output (e.g., fatigue, lightheadedness, dyspnea) attributable to lack of atrial contraction’s contribution to ventricular filling.
Unfavorable candidates include patients
(1) digitalis toxicity
(2) no symptoms and a well-controlled ventricular rate without therapy
(3) sinus node dysfunction and various unstable supraventricular tachyarrhythmias or bradyarrhythmias—often bradycardia-tachycardia syndrome—in whom AF finally develops and is maintained, which in essence represents a cure for sick sinus syndrome
(4) little or no symptomatic improvement with normal sinus rhythm
(5) prompt reversion to AF after cardioversion despite drug therapy
(6) a large (>5 cm) left atrium and longstanding AF
(7) episodes of AF that revert spontaneously to sinus rhythm
(8) no mechanical atrial systole after the return of electrical atrial systole
(9) AF and advanced heart block,
(10) cardiac surgery planned in the near future
(11) AAD intolerance
Embolic episodes are reported to occur in 1% to 3% of patients converted from AF to sinus rhythm.
Prior therapeutic anticoagulation with warfarin (international normalized ratio _______________ ) or newer agents such as dabigatran, rivaroxaban, apixaban or edoxaban, should be used consistently for at least _____________ by patients who have no contraindication to such therapy and have had AF for longer than __________________ duration.
INR 2.0 to 3.0
3 weeks
2 days or of indeterminate
Anticoagulation for at least _________________ afterward is recommended because restoration of atrial mechanical function lags behind that of electrical systolic function, and thrombi can still form due to delayed mechanical recovery, although the atria are electrocardiographically in sinus rhythm.
4 weeks
ST-segment elevation, sometimes d matic, can occur immediately after elective DC cardioversion and can last for up to ______________, although cardiac enzymes and myocardial scintigraphy may be unremarkable
1 - 2 minutes
ST elevation lasting longer than 2 minutes usually indicates myocardial injury unrelated to the shock.
ST elevation lasting longer than ___ minutes usually indicates myocardial injury unrelated to the shock
2 mins
Cardioversion of VT can also be achieved by a _____. Its mechanism of termination is probably related to a mechanically induced PVC that interrupts a tachycardia circuit and may be related to commotio cordis
Chest thump
Purpose is to destroy myocardial tissue by delivery of energy, generally electrical energy or cryoenergy, through electrodes on a catheter placed next to an area of the myocardium integrally related to onset or maintenance of the arrhythmia
Catheter ablation
RF energy causes resistive heating in the cells close to the tip of the catheter (i.e., these cells transduce the electrical energy into thermal energy). When tissue temperature exceeds 50°C, irreversible cellular damage and tissue death occur.
For tachycardias with an apparent focal origin (e.g., automatic, triggered activity, microreentry), the focus itself (<5 mm in diameter) is targeted. In macroreentrant AT and VT, inexcitable scar tissue typically separates strands of surviving myocardium, and wavefronts propagate around these scars. The target for ablation is a narrow portion of myocardium between inexcitable areas (e.g., scar, valve annulus
For tachy- cardias with an apparent focal origin (e.g., automatic, triggered activity, microreentry), the focus itself (<___ mm in diameter) is targeted
< 5 mm
When tissue temperature exceeds _____°C, irreversible cellular damage and tissue death occur.
50 C
An expanding front of conducted heat emanates from the region of resistive heating while RF delivery continues over the next 30 seconds and results in the production of a homogeneous, roughly hemispheric lesion of coagulative necrosis _____ mm in diameter
3-5mm
RF- induced heating of tissue that has inherent automaticity (e.g., His bundle, foci of automatic tachycardias) results in _____, whereas RF delivery during a reentrant arrhythmia typically causes slowing and termination of the arrhythmia
His bundle, foci of automatic tachycardias: Initial acceleration of a rhythm
Reentrant: slowing and termination
_______________ has been used to good advantage in cases in which standard (4-mm tip) catheter ablation has failed, as well as for primary therapy for atrial flutter and fibrillation and VT associated with structural heart disease, in which additional damage to already-diseased areas is not harmful and may be required to achieve the desired result.
Cooled-tip ablation
The safety, efficacy, and cost-effectiveness of RF catheter ablation of an accessory AV pathway have made ablation the treatment of choice in most adult and many pediatric patients who have ___________
AV reentrant tachycardia (AVRT) or atrial flutter or fibrillation associated with a rapid ventricular response over the accessory pathway
Most common mechanism of AVNRT?
Premature atrial complexes can encounter refractoriness in the fast pathway, conduct over the slow pathway, and reenter the fast pathway retrogradely, thereby initiating AV nodal reentrant SVT
_____________ ablation is rarely performed because it is associated with a prolonged PR interval, a higher recurrence rate (10% to 15%), and a slightly higher risk for complete AV block (2% to 5%)
Fast pathway
The slow pathway can be located by mapping along the__________________________ close to the coronary sinus os.
Posteromedial tricuspid annulus
The success rate is equivalent with the anatomic and electrographic mapping approaches, and most often, combinations of both are used and yield success rates of greater than 95%,
The surest endpoint for slow pathway ablation is ________________________, with and without an infusion of isoproterenol or epinephrine.
Elimination of sustained AVNRT
_______________________ is the preferred method for ablation of typical AVNRT.
Slow pathway approach
_______________________ is a rare form of SVT in which the ECG resembles that in AVNRT but is distinct in that (1) the mechanism is automatic, not reentrant, and (2) the atrium is clearly not involved in the tachycardia
Junctional tachycardia, often called ectopic junctional tachycardia
This disorder is most often observed in young healthy individuals, in women more often than in men, and is usually catecholamine dependent
Ablation must be carried out close to the His bundle, and the risk for heart block requiring pacemaker insertion exceeds 5%.
_____________________ is a syndrome characterized by high sinus rates with exercise and at rest. Patients complain of palpitations at all times of day that correlate with inappropriately high sinus rates.
Inappropriate sinus tachycardia
May not respond well to beta-blocker therapy because of lack of desired effect or occurrence of side effects.
Ablative lesions are usually placed between the superior vena cava and crista terminalis at sites of early atrial activation
When the sinus node area is to be ablated because of drug-refractory symptoms if IST, it can be identified anatomically and electrophysiologically, and ablative lesions are usually placed between the _____ at sites of early atrial activation
SVC
Crista terminalis
Patients with persistent inappropriate sinus tachycardia should be considered for ablation only after _____, because the results of ablation are often less than completely satisfactory.Whenever ablation is performed in the region of the sinus node, the patient should be apprised of the chance of needing a pacemaker after the procedure. ______ are also possibilities.
Clear failure of medical therapy
Phrenic nerve damage and superior vena caval stenosis
_______________ are a heterogeneous group of disorders; causative factors include rapid discharge of a focus (focal tachycardia) and reentry.
Atrial tachycardia
Focal tachycarida an occur in anyone, regardless of the presence of structural abnormalities of the atria, whereas reentrant ATs almost always occur in the setting of structurally damaged atria.
As noted, REENTRANT ATs usually occur in the setting of structural heart disease, especially after previous surgery involving an _____.
(1) Atrial incision (repair of congenital heart disease such as an atrial septal defect, Mustard or Senning repair of transposed great vessels or one of a variety of Fontan repairs for tricuspid atresia and other disorders)
(2) Previous atrial ablation (e.g., for AF).
FAT sites tend to cluster near the _________________ in the left atrium and the mouths of the atrial appendages and along the right atrial _____________
Pulmonary veins
Crista terminalis
Activation times at these sites typically occur only 15 to 40 milliseconds before onset of the P wave on the ECG. Care must be taken to avoid inadvertent damage to the phrenic nerve
Types of surgeries/procedures associated with reentrant atrial tachycardia
Previous surgery involving an atrial incision (repair of congenital heart disease such as an atrial septal defect, Mustard or Senning repair of transposed great vessels, or one of a variety of Fontan repairs for tricuspid atresia and other disorders), or previous atrial ablation
The ablation strategy in ATs is to identify regions with _____ atrial activation during tachycardia that can be proved by pacing techniques to be integral to the tachycardia
Mid-diastolic
Catheter ablation for ATs should be considered in patients who have _____.
Recurrent episodes of symptomatic sustained ATs that are:
(1) Drug resistant
(2) Drug intolerant
(3) Do not desire long-term drug treatment
Complications with ablation in ATs, which occur in 1% to 2% of patients, include _____.
Phrenic nerve damage
Cardiac tamponade
Heart block (with rare perinodal ATs)
The region of slow conduction is typically related to an ______________________
End of an atriotomy or previous ablation scar,
__________________ can be defined electrocardiographically (most typically, negative sawtooth waves in leads II, III, and aVF at a rate of approximately 300 beats/min) or electrophysiologically (rapid, organized macroreentrant AT, the circuit for which is anatomically determined).
Atrial Flutter
Atrial flutter can be defined electrocardiographically _____ or electrophysiologically _____.
ECG: most typically, negative sawtooth waves in leads II, III, and aVF at a rate of approximately 300 beats/min
EP: rapid, organized macroreentrant AT, the circuit for which is anatomically determined
Reentry in the right atrium, with the left atrium passively activated, constitutes the mechanism of the typical electrocardiographic variety of atrial flutter, with caudocranial activation along the right atrial septum and craniocaudal activation of the right atrial free wall
Typically, this is across the isthmus of atrial tissue between the inferior vena caval orifice and the tricuspid annulus (_____________________)
The cavotricuspid isthmus
Right atrial circuit is reversed (“clockwise” flutter proceeding cephalad up the right atrial free wall and caudad down the septum, with upright flutter waves in the inferior leads; These two arrhythmias constitute cavotricuspid isthmus–dependent flutter
The current end-point of ablation has changed to ensuring a line of ________________ is present in this region, usually by pacing from opposite sides of the isthmus
Bidirectional block
Candidates for RF catheter ablation in atrial flutter include patients with _____.
Recurrent episodes of atrial flutter that are drug resistant, those who are drug intolerant, and those who do not desire long-term drug therapy.
In some patients who have rapid ventricular rates despite optimal drug therapy during complex atrial tachyarrhythmias that are less amenable to ablation, RF ablation can be used to eliminate or modify _______________ and control the ventricular rates.
AV conduction
Improved left ventricular function can result from control of the ventricular rate during AF and withdrawal of rate-controlling medications that have negative inotropic action. Permanent right, His bundle or biventricular pacing is typically required after ablation.
Ablation and modification of AV conduction can be considered in the following cases
(1) patients with symptomatic atrial tachyarrhythmias who have inadequately controlled ventricular rates, unless primary ablation of the atrial tachyarrhythmia is possible (especially when a permanent pacemaker is already present for treatment of bradycardiatachycardia syndrome)
(2) similar patients when drugs are not tolerated or patients do not choose to take them, even though the ventricular rate can be controlled
(3) patients with symptomatic, nonparoxysmal junctional tachycardia that is drug resistant or in whom drugs are not tolerated or are not desired
(4) patients resuscitated from sudden cardiac death related to atrial flutter or AF with a rapid ventricular response in the absence of an accessory pathway
(5) patients with a dual-chamber pacemaker and pacemaker-mediated tachycardia that cannot be treated effectively by drugs or reprogramming of the pacemaker
_____________ occurs in patients with essentially structurally normal hearts and includes patients with isolated PVCs
Idiopathic VT
In general, the success rate for ablation of ______ is lower than that for AV node reentry or AV reentry
Ventricular tachycardia
Because of the heterogeneity of substrates and presentations. In the ideal case, induction of the VT must be reproducible, with uniform QRS morphology from beat to beat, and VT must be sustained and hemodynamically stable so that the patient can tolerate the VT long enough during the procedure to undergo the extensive mapping necessary to localize optimal ablation target sites
In the first group, VTs/PVCs can arise in either ventricle.
Right VTs most frequently originate in the __________ and have a characteristic ________________ morphology, _________ axis; less often, VTs/PVCs arise in the inflow tract or free wall.
Left VTs in structurally normal hearts are septal in origin and have a characteristic QRS configuration (i.e., ________________, _______________)
Outflow tract
Left bundle branch block–like, inferior axis morphology
Septal
Right bundle branch block, superior axis
Other VTs/PVCs also occur and arise from different areas of the left ventricle, including the left ventricular outflow region and the aortic sinuses of Valsalva, and are similar in electrocardiographic appearance and clinical behavior to those arising in the right ventricular outflow tract.
VTs in abnormal hearts without CAD can be the result of either ______, most often observed in patients with dilated cardiomyopathy, or as a focal process. Epicardial foci and circuits are more common in this than in other groups.
In patients with _________________, ablation of the right bundle branch eliminates the tachycardia.
Intramyocardial or bundle branch reentry
Bundle branch reentry
In scar-based VT (e.g., after MI, cardiomyopathies), finding a _____ used as a critical part of the reentrant circuit is desirable because ablation at this site has a good chance of eliminating the tachycardia. As a result of the extensive derangement in electrophysiology caused by the previous damage (e.g., infarct, myopathy), many areas of the ventricle may have diastolic activation but may not be relevant to perpetuation of the VT. These “bystander sites” make activation mapping more difficult.
Protected region of diastolic activation
Presystolic Purkinje potentials, as well as very-low-amplitude mid-diastolic signals, can be recorded during VT from sites at which ablation cures VT in most patients with ___________________________________; this VT characteristically terminates with _______________ and is the only significant idiopathic VT with a reentrant basis.
IV verapamil
Left ventricular VTs that have a right bundle branch block superior axis
True or False
Localization of optimal ablation sites for VT in patients with CAD and previous MI can be more challenging than in patients with structurally normal hearts because of the altered anatomy and electrophysiology.
True
Pace mapping has a lower sensitivity and specificity than for idiopathic VT. Furthermore, reentry circuits can sometimes be large and resistant to the relatively small lesions produced by RF catheter ablation in scarred endocardium.
________________ involves pacing for several complexes during a tachycardia at a rate slightly faster than the VT rate; after pacing is stopped and the same tachycardia resumes, the timing of the first complex relative to the last paced beat is an indicator of how close the pacing site is to a part of the VT circuit
Entrainment
Patients considered for RF catheter ablation of VT in the absence of structural heart disease are those with _____.
Symptomatic, sustained monomorphic VT when the tachycardia is drug resistant, when the patient is drug intolerant, or when the patient does not desire long-term drug therapy.
Patients with structural heart disease who are candidates for ablation include those with _____.
(1) Bundle branch reentrant VT
(2) Sustained monomorphic VT and an ICD who are receiving multiple shocks not manageable by reprogramming or concomitant drug therapy.I
In some patients (usually without structural heart disease,but also in patients with diseased ventricles), nonsustained VT or even severely symptomatic PVCs warrant RF catheter ablation.
In patients with structurally normal hearts, the success rate ofVT or PVC ablation is approximately _____%. In patients with postinfarction VT, more than _____% no longer have recurrences of VT after the ablation procedure despite inducibility of rapid VT or VF; only approximately 30% of patients will have no inducible ventricular arrhythmia of any type and no spontaneous recurrence
Structurally normal hearts: 85%
Postinfarction VT: 70%
Significant complications occur in up to 3%, including _____.
(1) Vascular damage
(2) Heart block
(3) Worsening of heart failure
(4) Cardiac tamponade
(5) Stroke
(6) Valve damage\
(7) Death is rare but can occur in patients with severe CAD and/or systolic dysfunction.
In patients with extensive structural heart disease, multiple VTs are usually present. Most of these patients already have, or soon will have, an ICD; ablation can be used to decrease the frequency of ICD therapies but is generally not intended to cure the patient of all ventricular arrhythmias.
Catheter ablation of a single VT in such patients may be only________________ and may not eliminate the need for further AAD or device therapy, but can improve quality of life by decreasing ICD shocks.
Palliative
In patients without structural heart disease, only a single VT is usually present, and catheter ablation of that VT is most often curative.
Cardiac sympathectomy (______) alters adrenergic influences on the heart and has been effective in some patients, particularly those who have recurrent VT with long-QT syndrome despite beta blockade, and catecholaminergic polymorphic VT.
Stellate ganglionectomy
The first direct surgical approach to VT was __________________, which entails performing a transmural ventriculotomy to isolate areas of endocardial fibrosis that were recognized visually; this procedure is rarely used now.
Encircling endocardial ventriculotomy
___________________ involves peeling off a 1- to 3-mm-thick layer of endocardium, often near the rim of an aneurysm, that has been demonstrated by mapping procedures to contain sites of mid-diastolic activation recorded during VT.
Subendocardial resection
In almost all patients who haveVT associated with ischemic heart disease, the arrhythmia, regardless of its configuration on the surface ECG, arises in the _____.
Left ventricle or on the left ventricular side of the interventricular septum
The procedure is usually performed through a limited thoracotomy, exposing only the area of the ventricles believed responsible for the arrhythmia. In idiopathic VT/PVC cases, this is often at the _____, an area where epicardial catheter ablation is difficult because of thick epicardial fat and proximity to major coronary arteries.
Basal aspect of the anterior left ventricle
