What is the management approach for a patient with hemochromatosis and cardiac involvement?

Management of Hemochromatosis with Cardiac Involvement

The primary management for hemochromatosis with cardiac involvement is aggressive iron removal therapy through phlebotomy or iron chelation, which can prevent, improve, or even reverse cardiac dysfunction. 1

Diagnostic Evaluation

• Clinical investigation should include evaluation of signs and symptoms of contractile dysfunction or conduction disease, ECG, Holter-ECG, and transthoracic echocardiography 1
• Cardiac MRI with T2* relaxation time measurement is the best method to assess myocardial iron overload, stratify risk, determine treatment intensity, and optimize follow-up 1
• Cardiologist consultation is recommended for any patient with signs of possible cardiac involvement 1, 2

Cardiac Manifestations to Monitor

• Early manifestations include restrictive cardiomyopathy with diastolic dysfunction that may progress to dilated cardiomyopathy with impaired systolic function 1, 3
• Conduction disturbances are common, including bradycardia, tachycardia, atrial fibrillation, ventricular arrhythmias, atrioventricular blocks, and risk of sudden death 1, 4
• Cardiac involvement varies by type of hemochromatosis, with higher prevalence in juvenile forms compared to HFE-related hemochromatosis 1

Treatment Approach

First-Line Treatment: Phlebotomy

• Weekly phlebotomy (removal of 450-500 mL of blood) is the first-line treatment for non-anemic patients 5, 3
• Target ferritin level during induction phase: 50 μg/L, but not lower to avoid iron deficiency 1, 6
• Maintenance phase: keep ferritin between 50-100 μg/L with less frequent phlebotomies (typically 2-6 times per year) 6, 5
• Monitor hemoglobin before each phlebotomy; reduce frequency if hemoglobin falls below 12 g/dL and temporarily discontinue if below 11 g/dL 6, 5

Second-Line Treatment: Iron Chelation

• Iron chelation therapy should be used when phlebotomy is not feasible or poorly tolerated, particularly in patients with anemia or severe cardiac impairment 1, 3
• Deferasirox (DFX) is the most studied oral chelator for hemochromatosis; recommended starting dose is 10 mg/kg 1
• Deferoxamine (DFO) can be used parenterally, especially in cases of severe cardiac iron overload 1, 7
• Combination therapy with oral deferiprone and intravenous deferoxamine has been described for severe cardiac iron overload, particularly in juvenile hemochromatosis 1, 7
• Careful monitoring is required with chelation therapy: monthly liver and renal function tests, and annual audiological and ophthalmological reviews 1

Special Considerations for Cardiac Involvement

• In patients with heart failure and arrhythmias, conventional cardiac treatment should be initiated per standard cardiology practice alongside iron removal therapy 1
• For patients with severe cardiac impairment who cannot tolerate standard phlebotomy, consider personalized mini-phlebotomies combined with chelation therapy 1
• Patients with severe cardiac manifestations should be referred to specialized centers for evaluation and treatment 1
• Calcium channel blockers may represent a potential adjunctive therapy as L-type Ca²⁺ channels provide a pathway for ferrous iron uptake into cardiomyocytes 8

Monitoring and Follow-up

• Regular cardiac assessment with echocardiography and/or cardiac MRI is recommended to monitor treatment response 1, 4
• More frequent monitoring is needed for juvenile forms of hemochromatosis due to higher risk of cardiac involvement 1
• Lifelong maintenance therapy is required to prevent recurrence of iron overload 5, 3

Important Pitfalls to Avoid

• Delaying treatment once cardiac involvement is detected can lead to rapid deterioration and poor outcomes 3, 9, 4
• Failing to recognize anemia in a hemochromatosis patient may indicate another underlying condition that requires investigation 1
• Vitamin C supplements should be avoided, especially before iron depletion, as they can increase iron absorption and toxicity 1, 6
• Patients with cirrhosis should abstain from alcohol completely to reduce complications associated with iron overload 6, 5

Early diagnosis and aggressive treatment are critical, as cardiac dysfunction is potentially reversible if effective therapy is introduced before the onset of overt heart failure 4, 8.