1. 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

2. 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

3. Disclosure
This speaker has no conflict of interest to disclose.

4. 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):

5. 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

6. 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

7. 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).

8. 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

9. 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:
Possible in high risk patients: chlorpromazine, haloperidol, olanzapine, risperidone, Unknown - quetiapine

10. 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)

11. 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

12. References
Van Noord, C. et al. Drug and non-drug-associated QT interval prolongation. Br J Clin Pharmacol, 2010; 70 (1):
Al-Khatib, SM et al. What Clinicians Should Know About the QT Interval. JAMA, 2003; 289(16):
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):
Drew BJ, et al. AHA Practice Standards for Electrocardiographic Monitoring in Hospital Settings. Circulation, 2004; 110: