What is the management approach for a patient with hydroxychloroquine (Plaquenil)-induced cardiomyopathy?

Management of Hydroxychloroquine-Induced Cardiomyopathy

Immediately discontinue hydroxychloroquine and initiate aggressive afterload reduction therapy, as cessation of the drug combined with heart failure management has been associated with halting disease progression and even clinical improvement. 1, 2

Immediate Actions

Drug Discontinuation

• Stop hydroxychloroquine immediately upon suspicion or confirmation of cardiotoxicity 3, 2
• Do not wait for biopsy confirmation if clinical suspicion is high, as irreversible histopathological changes can occur if discontinuation is delayed 4
• Recognize that cardiac toxicity can be fatal even after drug cessation if irreversible changes have already developed 4

Cardiac Assessment

• Obtain 12-lead ECG looking specifically for: 3, 4
  • Atrioventricular blocks (including Mobitz II) 5
  • Bundle branch blocks (right or left) 3
  • QT prolongation 3
  • Conduction system disease 4
• Perform transthoracic echocardiography to evaluate: 3, 4
  • Biventricular hypertrophy (concentric pattern) 6, 7
  • Systolic and diastolic dysfunction 2
  • Biatrial enlargement 5
  • Valvular regurgitation (mitral and tricuspid) 7
  • Restrictive filling patterns 2

Diagnostic Confirmation

Advanced Imaging

• Cardiac MRI with delayed gadolinium enhancement is the preferred non-invasive diagnostic tool 5, 7
• Look for characteristic findings: 7
  • Mid-wall, subepicardial, and patchy late gadolinium enhancement in non-ischemic distribution
  • Left ventricular wall thickening
  • Biventricular hypokinesis
  • Absence of edema and perfusion abnormalities
• Cardiac MRI may have prognostic value in assessing disease severity 4

Endomyocardial Biopsy

• Consider biopsy for definitive diagnosis when imaging is equivocal or to guide prognosis 2, 6, 7
• Characteristic pathologic findings include: 3, 7
  • Light microscopy: myocyte vacuolization, positive PAS stain with diastase sensitivity
  • Electron microscopy: myeloid and curvilinear bodies (inclusion bodies)
  • Phospholipidosis with accumulation of multilamellar zebra bodies
  • Association with phospholipidosis in absence of inflammation, infiltration, or necrosis 3

Heart Failure Management

Pharmacologic Therapy

• Initiate aggressive afterload reduction therapy 2
• Implement standard guideline-directed medical therapy for heart failure: 1
  • ACE inhibitors or ARBs for afterload reduction
  • Beta-blockers (titrate carefully given conduction abnormalities)
  • Diuretics for volume management
  • Aldosterone antagonists as appropriate
• Correct electrolyte imbalances (hypokalemia, hypomagnesemia) prior to and during treatment 3

Monitoring During Treatment

• Monitor cardiac function closely as clinical improvement can occur within months of drug cessation 5
• Serial echocardiography to assess: 2, 5
  • Ejection fraction improvement
  • Resolution of hypertrophy
  • Improvement in diastolic function
• Continuous ECG monitoring if conduction abnormalities present 4
• Track biomarkers (troponin, BNP) for recurrent elevations 4

Special Considerations

Arrhythmia Management

• Avoid QT-prolonging agents given hydroxychloroquine's potential for ventricular arrhythmias including torsades de pointes 3
• Consider implantable cardioverter-defibrillator if ventricular arrhythmias develop or ejection fraction remains severely reduced 4
• Pacemaker may be necessary for high-grade AV blocks 5

Prognosis and Outcomes

• Early detection and prompt discontinuation can lead to reversible disease 1, 5, 6
• Cases show improved ejection fraction and symptom resolution within months after drug cessation and supportive therapy 5
• However, sudden death can occur even after clinical improvement, particularly if irreversible histopathological changes occurred before discontinuation 4
• Long-term follow-up is essential as disease progression may continue even after drug cessation 3

Prevention in Other Patients

Screening Recommendations

• Regular screening with 12-lead ECG and transthoracic echocardiography should be considered in all hydroxychloroquine-treated patients 4
• Risk factors for cardiotoxicity include: 1, 3
  • High cumulative exposure (>5 mg/kg/day actual body weight)
  • Treatment duration >5 years
  • Renal impairment (eGFR <60 ml/min per 1.73 m²)
  • Concomitant use of other cardiotoxic agents