What are the considerations for using hydroxychloroquine (Plaquenil) in patients with cardiomyopathy?

Hydroxychloroquine and Cardiomyopathy: Considerations for Use

Hydroxychloroquine should be avoided in patients with pre-existing cardiomyopathy due to the risk of fatal cardiotoxicity, including worsening heart failure, conduction abnormalities, and ventricular arrhythmias. 1

Cardiac Risks of Hydroxychloroquine

Hydroxychloroquine (HCQ) carries significant cardiac risks that require careful consideration, particularly in patients with cardiomyopathy:

Cardiotoxicity Mechanisms

• Can cause fatal and life-threatening cardiotoxicity, including cardiomyopathy 1
• Associated with phospholipidosis in the myocardium (demonstrated on endomyocardial biopsy) 1
• Presents as an acquired lysosomal storage disorder with chronic use 2
• May lead to both restrictive and dilated cardiomyopathy patterns 3, 4

Specific Cardiac Manifestations

• Ventricular hypertrophy (biventricular)
• Pulmonary hypertension
• Conduction disorders including:
  • Sick sinus syndrome
  • Atrioventricular block
  • Bundle branch blocks
• QT interval prolongation with risk of ventricular arrhythmias (including torsades de pointes) 1

Absolute Contraindications

Hydroxychloroquine is absolutely contraindicated in patients with:

• Congenital or acquired QT prolongation
• Heart failure
• History of myocardial infarction
• Bradycardia (<50 bpm)
• History of ventricular dysrhythmias
• Uncorrected electrolyte abnormalities (hypokalemia/hypomagnesemia)
• Concurrent use of other QT-prolonging medications 1

Monitoring Recommendations if HCQ Must Be Used

If hydroxychloroquine must be used in patients with mild cardiac disease or risk factors (when benefits clearly outweigh risks):

Before Initiation

• Baseline ECG to assess QT interval and conduction system
• Baseline echocardiography to assess ventricular function
• Electrolyte panel (potassium, magnesium) 5, 1

During Treatment

• Regular ECG monitoring (yearly at minimum, more frequently with cardiac risk factors) 5
• Regular echocardiography to detect early signs of cardiomyopathy 4
• Monitor for symptoms of heart failure or arrhythmias:
  • Dyspnea
  • Fatigue
  • Palpitations
  • Syncope or pre-syncope 1

Dose Considerations

• Never exceed 5 mg/kg/day of actual body weight 1
• Lower doses should be considered in patients with any cardiac risk factors
• Shorter duration of treatment when possible (risk increases with duration) 1

Warning Signs Requiring Immediate Discontinuation

Hydroxychloroquine should be immediately discontinued if any of these occur:

• New or worsening heart failure symptoms
• New conduction abnormalities on ECG
• QT prolongation
• Ventricular arrhythmias
• Decline in ventricular function on echocardiography 1, 4

Diagnostic Approach for Suspected Cardiotoxicity

If hydroxychloroquine cardiotoxicity is suspected:

1. Obtain ECG to assess for conduction abnormalities and QT prolongation
2. Perform echocardiography to evaluate ventricular function and morphology
3. Consider cardiac MRI which may show specific patterns of myocardial damage
4. Endomyocardial biopsy can confirm the diagnosis with characteristic findings:
   • Myocyte hypertrophy with vacuolar changes
   • Abnormal mitochondria
   • Myeloid and curvilinear bodies 6

Prognosis and Management of HCQ-Induced Cardiomyopathy

• Early cardiotoxicity may be reversible with prompt drug discontinuation 2
• Advanced cardiotoxicity may be irreversible despite drug discontinuation
• Treatment includes standard heart failure therapy according to guidelines
• Some patients may require advanced heart failure therapies or transplantation in severe cases 4, 2

Key Considerations for Specific Patient Populations

Patients with Autoimmune Conditions

• The American College of Rheumatology notes that while HCQ cardiac toxicity is rare in rheumatic diseases, it can be fatal 7
• Benefits may outweigh risks in patients with SLE without cardiac disease, as HCQ reduces disease activity 5
• Alternative immunomodulatory therapies should be considered for patients with cardiomyopathy

Patients with SLE

• SLE itself can cause myocarditis and cardiomyopathy in up to 9% of patients 5
• Hydroxychloroquine-induced cardiomyopathy must be distinguished from SLE-related cardiac disease
• Consider alternative treatments such as corticosteroids, azathioprine, or cyclophosphamide for SLE patients with cardiac involvement 5

In conclusion, the cardiac risks of hydroxychloroquine, particularly in patients with pre-existing cardiomyopathy, generally outweigh the benefits. Alternative therapies should be strongly considered, and if hydroxychloroquine must be used, close cardiac monitoring is essential.