Implications for safe medication prescribing in older adults QTc Prolongation Implications for safe medication prescribing in older adults Staci Hollar MD Geriatrician St. Vincent Center for Healthy Aging

Biography Undergraduate degree from DePauw University Indiana University School of Medicine Internal Medicine Residency at St. Vincent Hospital Geriatric Medicine Fellowship at the St. Vincent Center For Healthy Aging Geriatrician at St. Vincent Center for Healthy Aging

Disclosure This speaker has no conflict of interest to disclose.

What is the QT Interval? JAMA. 2003;289(16):2120-2127. -Starts at the beginning of the QRS complex and ends at the end of the T wave. -Represents ventricular depolarization and repolarization. -If there is an excess of positively charged ions, repolarization is extended and the QT interval is prolonged. -There is some variability in measuring this interval and it can change with heart rate (prolonged at lower heart rates). Formulas exist for adjusting for this but there are differences in opinion on which is the best method. -Current recommendations for measurement: Measure manually using a limb lead, from beginning of QRS to end of Twave, average over 3-5 beats, measurement during peak plasma concentration of a qt prolonging drug, Adjust for heart rate using some method. If Afib present, use average of shortest and longest beats as above. JAMA. 2003;289(16):2120-2127.

Prolonged QTc and Risk >450 ms in men, >470 ms in women In the absence of intraventricular conduction delay Prolonged QTc interval increases risk for polymorphic ventricular tachycardia (Torsades de Pointe) Palpitations Syncope Seizures Sudden Cardiac Death UpToDate.com

Incidence Difficult to assess Most data from case reports or small observational studies One single center review: 293 of 41,649 admissions had QTc >500ms Less than 6% of those experienced syncope or arrhythmia Observational study in the Netherlands 24 of 775 patients with sudden cardiac death were on QT prolonging agent Current use of any non-cardiac QT prolonging agent associated with significantly increased risk of sudden cardiac death Highest with antipsychotics

Congenital vs Acquired Congenital Long QT Jervell and Lange-Nielsen Syndrome Romano Ward Syndrome LQT1 and LQT2 due to mutations in potassium channels LQT3 due to mutation in sodium channels Idiopathic Acquired Long QT Medications Electrolyte abnormalities Hypokalemia Hypomagnesemia Hypocalcemia Structural Heart Disease Bradyarrhythmia -Probably often a combination of genetic and environmental factors in many cases (possible that patients with acquired long QT have genetic predisposition, silent gene mutations).

Risk Factors for Drug Induced Long QTc High doses of offending agents Rapid IV infusion of offending agent Use of more than one QT prolonging agent Concurrent use of a drug that slows metabolism through cytochrome P450 enzymes Diuretic use Electrolyte abnormalities (hypokalemia, hypomagnesemia) Hepatic or renal dysfunction Underlying heart disease (CHF, MI, LVH) Female sex Advanced Age

Medications Antiarrhythmic Drugs Certain Psychotropics Amiodarone, Sotalol, Quinidine, Procainamide, Dofetilide Certain Psychotropics Thioridazine, Ziprasidone, Pimozide Certain Antimicrobials Clarithromycin, Erythromycin, Pentamidine, Fluoroquinolones Certain Antidepressants Amitriptyline, Desipramine, Imipramine, Citalopram, Venlafaxine Certain Gastric Motility Agents Cisapride now off market Methadone For a more extensive list: www.crediblemeds.org Possible in high risk patients: chlorpromazine, haloperidol, olanzapine, risperidone, Unknown - quetiapine

So how does this affect prescribing? Weigh risks vs benefits of therapy Is there an alternative medication with similar benefit? Will the medication improve survival, symptoms, morbidity? Assess risk for QT prolongation Patient risk factors Concurrent medications Drug properties (ex. Renally excreted, CYP450 interactions)

Monitoring EKG monitoring Management Before and after starting antiarrhythmic agent Typically require inpatient monitoring during antiarrhythmic initiation Anyone who overdoses on potentially proarrhythmic agent New onset bradyarrhythmia Severe electrolyte abnormalities Consider before and after starting antipsychotic Consider in patients with multiple risk factors for prolonged QT Including being on multiple agents that can prolong QT Management If QT prolongs >60ms above baseline, or is >500ms Consider stopping new medication Consider alternative options in high risk patients prior to initiating QT prolonging agent Try to avoid multiple QT prolonging agents Educate patients on symptoms to watch for Consider monitoring electrolytes

References Van Noord, C. et al. Drug and non-drug-associated QT interval prolongation. Br J Clin Pharmacol, 2010; 70 (1): 16-23. Al-Khatib, SM et al. What Clinicians Should Know About the QT Interval. JAMA, 2003; 289(16): 2120-27. Berul, C. Acquired Long QT Syndrome: Definitions, Causes and Pathophysiology. Up To Date. (Accessed January 30, 2019). Yu H, et al. Acquired long QT Syndrome in Hospitalized Patients. Heart Rhythm, 2017, 14: 974. Strauss, SM et al. Non-cardiac QTc-prolonging drugs and risk of sudden cardiac death. Eur Heart J 2005; 26: 2007. Berul, C. Acquired Long QT Syndrome: Clinical Manifestations, Diagnosis and Management. Up To Date (Accessed January 30, 2019). Drew BJ, et al. AHA/ACCF Prevention of Torsade de Pointes in Hospital Settings. Circulation, 2010; 121(8):1047-60. Drew BJ, et al. AHA Practice Standards for Electrocardiographic Monitoring in Hospital Settings. Circulation, 2004; 110:2721-46.