Treatment of Ventricular Arrhythmias WS 2023 PDF

TREATMENT OF VENTRICULAR ARRHYTHMIAS Jodi L. Taylor, Pharm.D., BCCCP, BCPS, FASHP 1 Current Guidelines 2017 AHA/ACC/HRS Guideline for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death – Circulat...

TREATMENT OF VENTRICULAR ARRHYTHMIAS Jodi L. Taylor, Pharm.D., BCCCP, BCPS, FASHP 1 Current Guidelines 2017 AHA/ACC/HRS Guideline for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death – Circulation 2018;138:e272-e391 2022 ESC Guidelines for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death – Eur Heart J 2022; doi:10.1093/eurheartj/ehac.262 Looking Ahead in the Curriculum Advanced Cardiovascular Life Support will be covered in Pharmacotherapy V. 2  Learning Objectives Design appropriate pharmacological treatment regimens for prophylaxis and treatment of ventricular arrhythmias. Recognize risk factors for shock after myocardial infarction indicating a delay in early beta blocker therapy as appropriate. Discuss the importance of the CAST trial. Identify drugs commonly associated with QT prolongation. Identify patients who meet criteria indicating an increased risk for Torsades de Pointes. 3 Definitions Term Definition Ventricular tachycardia (VT) Cardiac arrhythmia of > 3 consecutive complexes originating in the ventricles at a rate > 100 bpm Sustained VT VT lasting > 30 seconds or VT that requires termination due to hemodynamic compromise in < 30 seconds Nonsustained VT VT that terminates spontaneously Monomorphic VT VT with a stable, single QRS morphology (aka shape) from beat to beat Polymorphic VT VT with changing or multiform QRS morphology from beat to beat Torsades de Pointes (TdP) Polymorphic VT in the setting of a long QT interval characterized by waxing and waning QRS amplitude 4 Definitions Term Definition Ventricular fibrillation (VF) Rapid, grossly irregular electrical activity with marked variability in ECG waveform with ventricular rate usually > 300 bpm Sudden Cardiac Arrest (SCA) Sudden cessation of cardiac activity such that the victim becomes unresponsive with agonal gasps or no signs of respirations and no signs of circulation Sudden Cardiac Death (SCD) Sudden and unexpected death occurring within an hour of the onset of symptoms or patients found dead within 24 hr of being asymptomatic, presumed due to cardiac arrhythmia or hemodynamic catastrophe 5  Classifications of Ventricular Arrhythmias Classification by Clinical Presentation Classification by Electrocardiography Zipes DP, et al. Circulation 2006;114:e385 6  Classifications of Ventricular Arrhythmias Clinical Presentation – Hemodynamically stable Asymptomatic or minimal symptoms – Hemodynamically unstable Presyncope Syncope Sudden cardiac death (SCD) Sudden cardiac arrest Zipes DP, et al. Circulation 2006;114:e385 7  Hemodynamically Unstable Presentation Presyncope – Reported/described as: Dizziness Lightheadedness Feeling faint “graying out” Syncope – Sudden loss of consciousness with loss of postural tone (not related to anesthesia) with spontaneous recovery Zipes DP, et al. Circulation 2006;114:e385 8  Hemodynamically Unstable Presentation Treatment of patients who present with hemodynamically unstable ventricular arrhythmias should be treated in accordance with the 2020 AHA/ECC ACLS Guidelines – This includes SCA, SCD & VF Pulseless ventricular arrhythmias require defibrillation No pulse = start CPR! SCA=sudden cardiac arrest, SCD=sudden cardiac death, VF=ventricular fibrillation Panchal AR, et al. Circulation 2020;142:S366 9  Hemodynamically Stable Presentation Asymptomatic Minimal symptoms – Palpitations Reported as felt in either chest, throat, or neck and described as: – Heartbeat sensations that feel like pounding or racing – An unpleasant awareness of heartbeat – Feeling of skipped beats or a pause Zipes DP, et al. Circulation 2006;114:e385 10  Classification of Ventricular Arrhythmias Classification by Electrocardiography – Ventricular tachycardia (VT) Monomorphic – Sustained – Nonsustained Polymorphic – Sustained – Nonsustained – Torsades de pointes (TdP) – Ventricular fibrillation Zipes DP, et al. Circulation 2006;114:e385 11 Monomorphic VT EKG Criteria – Wide QRS complex – No P waves seen – All depolarizations from one focus 12 Polymorphic VT EKG Criteria – Wide QRS complex – No P waves seen – Depolarizations from many foci 13 Torsades de Pointes EKG Criteria – Wide QRS complex – No P waves seen – Complexes “twist” around axis 14 Ventricular Arrhythmias Prophylaxis Treatment 15  Prevention of Sudden Cardiac Death Public access defibrillation available Prompt bystander-provided CPR Promote community BLS training Mobile-based alerts to BLS-trained bystander volunteers Zeppenfeld K, et al. Eur Heart J 2022; doi:10.1093/eurheartj/ehac.262 16 Prophylaxis of Ventricular Arrhythmias Optimize guideline-directed medical therapy for comorbidities – Heart failure – CAD/ASCVD 17  Prophylaxis of Ventricular Arrhythmias Beta blockers (BB) are the only class that have demonstrated a reduction in mortality from primary or secondary prevention of SCD – Early use of BB in post-MI patients with RF for shock is associated with an increased risk of shock or death. Risk Factors for Shock post-MI Age > 70 years Symptoms < 12 hours with STEMI SBP < 120 mmHg HR > 110 bpm Al-Khatib SM, et al. Circulation 2018;138:e272 18  Prophylaxis of Ventricular Arrhythmias Class I AAR Agents Limited role in prevention due to the CAST trial IV Lidocaine Do not use in ACS with the intent to prevent VT from occurring Use for treatment of VT will be discussed separately Al-Khatib SM, et al. Circulation 2018;138:e272 Hallstrom AP, et al. N Engl J Med 1989;321:406 Echt DS, et al. N Engl J Med 1991;324:781 19  Cardiac Arrhythmia Suppression Trial Hypothesis: Suppression of ventricular ectopy after MI reduces sudden death Inclusion Criteria: AMI between 6 days and 2 years prior 1498 Patients to screening Average of 6 or more ventricular premature depolarizations/hr No runs of VT of > 15 beats EF < 55% if MI within 90 days from 755 received enrollment 743 received encainide or EF < 40% if MI > 90 days from placebo flecainide enrollment Methods: Patients were eligible to add Outcome Active Drug Placebo P-value on moricizine as a 2nd drug Death due to arrhythmia 5.7% (43) 2.2 % (16) 0.0004 Conclusion: An excess of cardiac deaths occurred in the active treatment group Death due to other cardiac cause 2.3% (17) 0.7% (5) 0.01 Echt DS, et al. N Engl J Med 1991;324:781 20 Ventricular Arrhythmias Prophylaxis Treatment 21 Treatment of Ventricular Arrhythmias Withdraw offending agents if drug-induced arrhythmia is suspected Investigate for reversible causes – Electrolyte imbalances – Ischemia – Hypoxemia – Others 22  Sustained, HD-Stable Monomorphic VT For Patients with Structural Heart Disease Consider disease- specific Cardioversion Drug Therapy treatments IV Procainamide (IIa) recommended over IV Amiodarone (IIb) or IV Sotalol (IIb) Al-Khatib SM, et al. Circulation 2018;138:e272 23  Treatment of Ventricular Arrhythmias Potassium Channel Blockers – Amiodarone Can be used to terminate HD-stable VT Chronic therapy associated with significant risks – Sotalol Can be used to terminate HD-stable VT Significant proarrhythmic effects May lead to HF exacerbation and questionable effect on mortality in post-MI patients with HFrEF – Bretylium Reintroduced to market in 2020 Al-Khatib SM, et al. Circulation 2018;138:e272 24 Treatment of Ventricular Arrhythmias Bretylium – Not included most recent guidelines – 2010 ACLS Guidelines recommended against use – Key takeaways Onset of action may be delayed for 20 minutes or more Should not be considered unless last resort for arrhythmias resistant to other therapies May initially cause hypertension, but quickly followed by hypotension Can cause significant hyperthermia, significant N/V Don’t use in digoxin toxicity Not for supraventricular arrhythmias Can only use for 3-5 days 25  Treatment of Ventricular Arrhythmias Sodium Channel Blockers – Use generally avoided due to CAST trial – Specific circumstances for use: Can be used to terminate HD-stable VT – Procainamide Refractory VT/cardiac arrest that is witnessed – Lidocaine Congenital LQTS – Mexiletine Brugada syndrome – Quinidine Catecholaminergic polymorphic VT – Flecainide – Ranolazine – late Na channel current blockade and blockade of the delayed rectifier potassium current Lack of convincing clinical data to support use at this time Al-Khatib SM, et al. Circulation 2018;138:e272 26  Treatment of Ventricular Arrhythmias Calcium Channel Blockers – No evidence-based role – IV verapamil for sustained VT associated with HD collapse – Avoid in HFrEF and acute MI patients Al-Khatib SM, et al. Circulation 2018;138:e272 27  Treatment of Ventricular Arrhythmias Electrolytes – Goal Potassium between 3.5 and 4.5 mEq/L Guidelines recognize that some replace potassium to 4.5-5 mEq/L K < 3 mEq/L or > 5 mEq/L likely harmful – Avoid hypomagnesemia No benefit to drive magnesium to supratherapeutic levels Al-Khatib SM, et al. Circulation 2018;138:e272 Cohn JN, et al. Arch Intern Med 2000;160:2429 Leier CV, et al. Am Heart J 1994;128:564 28 Torsades de Pointes Congenital LQTS Advanced Drug- conduction associated disease 29  Congenital LQTS Clinical Assessment Clinical Course Genetic testing on all first- Variable depending on age, degree family members* genotype, gender, Careful and thorough H&P environmental factors, and Distinguish between therapy congenital and acquired Continuous risk assessment factors warranted *Genetic counseling recommended prior to genetic testing. Zipes DP, et al. Circulation 2006;114:e385 30  EKG Interpretation of QT Interval Reported as QT and QTc on EKG reports – QT Mean value from at least 3-5 cardiac cycles Measured from earliest onset of QRS complex to the end of the T wave Measurement made from leads II and V5 or V6 with the longest value being used – QTc QT value corrected for heart rate Bazett formula – QTc = QT/RR0.5 Zipes DP, et al. Circulation 2006;114:e385 31  EKG Interpretation of QT Interval Suggested Values for Diagnosing QT Prolongation Rating 1-15 years Adult Male Adult Female Normal < 440 < 430 < 450 Borderline 440-460 430-450 450-470 Prolonged > 460 > 450 > 470 Zipes DP, et al. Circulation 2006;114:e385 32  Drugs that prolong the QT-interval www.crediblemeds.org Drugs Removed from Market or Severely Restricted due to QT Prolongation Terfinadine Astemizole Grepafloxicin Terodiline Droperidol Lidoflazine Sertindole Levomethadyl Cisapride Pimozide 33  Risk Factors for Drug-Induced Torsades de Pointes Female sex Hypokalemia Bradycardia Recent conversion from AF, esp with a QT-prolonging drug CHF Digitalis therapy High drug concentrations (except quinidine) Rapid rate of IV infusion with a QT-prolonging drug Baseline QT prolongation Subclinical LQTS Ion-channel polymorphisms Severe hypomagnesemia Zipes DP, et al. Circulation 2006;114:e385 34  Drugs Implicated in TdP Antiarrhythmic drugs Class Ia drugs Class III drugs Bepridil Promotility drugs Antimicrobials Macrolides Fluoroquinolones Antiprotozoals/malarials Antipsychotic drugs Phenothiazines Butyrophenones Pimozide Miscellaneous drugs/Poisons Arsenic trioxide Methadone Organophosphates Vitamins, Supplements, and Herbals Cesium Licorice Zhigancao Zipes DP, et al. Circulation 2006;114:e385 35  Conditions Associated with TdP Electrolyte Disturbances Hypokalemia Hypomagnesemia Hypocalcemia Conduction Disorders Complete AV block Sick Sinus Syndrome GI Conditions/Disorders Anorexia nervosa “Liquid Protein” diets Gastroplasty Ileojejunal bypass DKA HHS Nervous System Injury Subarachnoid hemorrhage Thalamic hematoma Right Neck Dissection Right neck hematoma Pheochromocytoma Zipes DP, et al. Circulation 2006;114:e385 36  Treatment of Torsades de Pointes First-line Magnesium sulfate 1-2g IV Withdraw offending agents Correct electrolyte abnormalities [replete K > 4 mEq/L, magnesium > 2 mEq/L Second-line If magnesium does not suppress TdP, increase the heart rate with atrial or ventricular pacing or isoproterenol Al-Khatib SM, et al. Circulation 2018;138:e272 37 Prevention is Key!! Drew BJ, et al. Circulation 2010;121:1047-1060 ECG Signs indicative of risk: Increase in QTc from pre-drug baseline of 60 msec Marked QTc prolongation > 500 msec T-U wave distortion that becomes more exaggerated in the beat after a pause Visible T-wave alternans New-onset ventricular ectopy Couplets Nonsustained polymorphic VT initiated in the beat after a pause 38  Other Recommendations for Patients with VA Digoxin Toxicity – Digoxin antibodies is recommended for those who present with sustained VA due to digoxin toxicity – Magnesium can be beneficial in the treatment of VT secondary to digoxin toxicity – Temporary pacing may be needed Smoking – Smoking should be STRONGLY discouraged in all patients with suspected or documented ventricular arrhythmias and/or aborted SCD. Lipids – Statin therapy is beneficial in those with ASCVD – Omega-3 FA may be considered for patients with CHD Icosapent ethyl (Vascepa®) was shown to reduce the risk of CV events [including CV death] in statin-treated patients with [established CV disease] or [DM + 1 RF for CV disease] – Results may influence future guideline recommendations Al-Khatib SM, et al. Circulation 2018;138:e272 Zipes DP, et al. Circulation 2006;114:e385 Bhatt DL, et al. N Engl J Med 2019;380:11 39