Cardiac Effects of Hydroxychloroquine
Hydroxychloroquine (HCQ) has significant cardiac effects including QT prolongation, ventricular arrhythmias (including torsades de pointes), cardiomyopathy, and conduction disorders that can lead to increased morbidity and mortality, requiring careful monitoring and risk assessment before and during treatment. 1
Major Cardiac Risks of Hydroxychloroquine
QT Prolongation and Arrhythmias
- HCQ has a potential to prolong the QT interval, which can lead to ventricular arrhythmias including torsades de pointes 1
- Approximately 10% of patients treated with HCQ develop QT prolongation 2
- Risk factors for QT prolongation include:
- Congenital or acquired QT prolongation
- Cardiac disease (heart failure, myocardial infarction)
- Bradycardia (<50 bpm)
- History of ventricular dysrhythmias
- Uncorrected hypokalemia and/or hypomagnesemia 1
Cardiomyopathy
- Fatal and life-threatening cases of cardiotoxicity, including cardiomyopathy, have been reported with HCQ treatment 1
- Chronic use can result in an acquired lysosomal storage disorder leading to cardiomyopathy characterized by:
- Concentric hypertrophy
- Conduction abnormalities
- Increased adverse clinical outcomes and mortality 3
- Endomyocardial biopsy often shows phospholipidosis in the absence of inflammation, infiltration, or necrosis 1
Clinical Presentation
- Patients may present with:
- Ventricular hypertrophy
- Pulmonary hypertension
- Conduction disorders including sick sinus syndrome
- ECG findings including atrioventricular, right or left bundle branch block 1
Risk Factors for Cardiac Complications
Patient-Specific Factors
- Chronic kidney disease (CKD) 4
- History of atrial fibrillation 4
- Heart failure 4
- Advanced age and female sex 5
- Baseline QTc prolongation (≥500 ms) 5
- Congenital long QT syndrome 5
Medication-Related Factors
- Higher risk with concomitant QT-prolonging medications 1
- Particular caution with:
- Other macrolides (e.g., azithromycin)
- Quinolones
- Tyrosine kinase inhibitors (TKIs)
- Doxorubicin
- Ondansetron
- Serotonin reuptake inhibitors 6
- High-dose regimens (daily doses exceeding 5 mg/kg actual weight) 1
- Longer duration of treatment 1
Monitoring Recommendations
Pre-Treatment Assessment
- Obtain baseline ECG to assess for pre-existing QT prolongation 5
- Review medication list for other QT-prolonging drugs 5
- Check electrolyte levels, particularly potassium and magnesium 5
- Screen for history of heart disease, slow pulse rate, family history of sudden death 5
During Treatment
- Monitor cardiac function as clinically indicated 1
- Perform follow-up ECG during therapy, especially in high-risk patients 5
- Consider ECG monitoring at 5 and 10 days after starting treatment 6
- Maintain normal electrolyte levels 5
- Monitor for signs and symptoms of cardiac compromise 1
Management of Cardiac Complications
QT Prolongation
- Do not exceed recommended dosages as QT prolongation risk increases with higher drug concentrations 1
- Correct electrolyte imbalances before and during use 1
- Discontinue HCQ if significant QT prolongation occurs 1
Arrhythmias
- If bradycardia occurs, discontinue HCQ and monitor cardiac rhythm 5
- Consider temporary pacing in severe cases of bradycardia 5
- Isoproterenol may be used to increase heart rate in emergency situations 7
Cardiomyopathy
- Discontinue HCQ immediately if cardiomyopathy is suspected or demonstrated 1
- Early withdrawal is essential due to potential reversibility of cardiomyopathy 3
- Consider cardiac MRI and endomyocardial biopsy to confirm diagnosis in suspected cases 3
Special Considerations
COVID-19 Treatment
- Higher risk of cardiac events observed in COVID-19 patients treated with high-dose HCQ 6
- In a randomized, double-blinded trial, high-dose chloroquine (600 mg twice daily) showed increased QTc prolongation and mortality compared to lower doses 6
- Daily ECG monitoring and risk mitigation strategies should be considered when using HCQ for COVID-19 2
Long-term Treatment
- Regular screening with 12-lead ECG and echocardiography should be considered for patients on long-term HCQ therapy 3
- QTc >470 ms during HCQ treatment has been associated with increased mortality risk 4
- Approximately 7% of patients on long-term HCQ therapy develop QTc 470-500 ms, and 1.5% develop QTc >500 ms 4
By understanding these cardiac effects and implementing appropriate monitoring strategies, clinicians can minimize the cardiac risks associated with hydroxychloroquine therapy while still providing necessary treatment for indicated conditions.