What is the treatment approach for patients with hemochromatosis (iron overload disorder) and heart failure?

Treatment of Hemochromatosis with Heart Failure

Patients with hemochromatosis and heart failure require aggressive iron removal therapy with therapeutic phlebotomy as first-line treatment (targeting ferritin 50-100 μg/L) combined with standard heart failure medications, but when phlebotomy is not tolerated due to anemia or hemodynamic instability, iron chelation therapy with deferoxamine or deferasirox should be initiated immediately. 1, 2

Initial Assessment and Risk Stratification

Before initiating treatment, obtain cardiac MRI with T2* relaxation time measurement to quantify myocardial iron burden and stratify cardiac risk 1, 2:

• T2 >20 ms (green zone)*: Low risk for imminent heart failure 1
• T2 10-20 ms (yellow zone)*: Intermediate risk requiring close monitoring 1
• T2 <10 ms (red zone)*: High risk requiring immediate aggressive chelation therapy 1

Perform comprehensive cardiac evaluation including ECG, Holter monitoring, and echocardiography to assess for arrhythmias, diastolic dysfunction, and systolic impairment 2, 3. Cardiologist consultation is mandatory for any patient with cardiac involvement 2.

First-Line Treatment: Therapeutic Phlebotomy

Induction Phase

• Remove 450-500 mL of blood (200-250 mg iron) weekly as tolerated 1, 4, 5
• Check hemoglobin/hematocrit before each session; do not allow hemoglobin to fall below 80% of baseline 4, 5
• If hemoglobin drops below 12 g/dL, reduce frequency; if below 11 g/dL, pause treatment 4
• Monitor serum ferritin every 10-12 phlebotomies (approximately every 3 months) 5
• Target ferritin: 50 μg/L during initial depletion 2, 4

Maintenance Phase

• Continue phlebotomy 2-6 times per year to maintain ferritin between 50-100 μg/L 1, 2, 4
• Monitor ferritin and transferrin saturation every 6 months 4

Evidence for Cardiac Improvement

Improvements in cardiac function and refractory arrhythmias have been documented with aggressive phlebotomy, especially when started early 1. However, patients with severe cardiac impairment may not tolerate standard phlebotomy due to hemodynamic instability 2.

Second-Line Treatment: Iron Chelation Therapy

When to Use Chelation

Iron chelation is indicated when 1, 2:

• Phlebotomy is not feasible due to anemia
• Severe cardiac impairment with hemodynamic instability
• Poor venous access
• Patient intolerance to phlebotomy

Chelation Options

Deferoxamine (Parenteral):

• Dose: 20-40 mg/kg/day via continuous subcutaneous infusion for 8-12 hours nightly, 5-7 nights weekly 1
• Maximum urinary iron excretion achieved at approximately 2 g per 24 hours 1
• Preferred in secondary iron overload with dyserythropoiesis 1
• Limitations include cost, parenteral route, discomfort, and neurotoxicity 1

Deferasirox (Oral):

• Starting dose: 10 mg/kg/day 2, 6
• Contraindicated in patients with eGFR <40 mL/min/1.73 m² and severe (Child-Pugh C) hepatic impairment 7
• Requires monthly monitoring of liver and renal function, with weekly renal monitoring during first month 7
• Annual audiological and ophthalmological reviews mandatory 2
• Common adverse events include diarrhea, headache, nausea, and dose-dependent increases in ALT and creatinine 6
• Can reduce serum ferritin by 63-75% at doses of 5-15 mg/kg/day over 48 weeks 6

Special Considerations for Cardiac Patients

For patients in the "red zone" (T2* <10 ms) with heart failure symptoms, aggressive chelation therapy must be combined with standard heart failure medications including ACE inhibitors, diuretics, and beta-blockers 1. In severe cases with anemia, consider personalized mini-phlebotomies combined with chelation therapy 2.

Concurrent Heart Failure Management

Initiate standard heart failure therapy alongside iron removal 1, 2:

• ACE inhibitors or ARBs
• Beta-blockers
• Diuretics for volume management
• Treat arrhythmias per standard cardiology practice

Critical Monitoring Parameters

During Treatment

• Renal function: Measure serum creatinine in duplicate at baseline; monitor at least monthly, weekly during first month if using deferasirox 7
• Hepatic function: Check transaminases and bilirubin every 2 weeks during first month, then monthly 7
• Cardiac assessment: Regular echocardiography and/or cardiac MRI to monitor treatment response 2
• Ferritin: Monthly monitoring to guide dose adjustments 1, 4

Risk of Overchelation

When ferritin falls below 1000 μg/L on two consecutive visits, consider dose reduction, especially if deferasirox dose exceeds 17.5 mg/kg/day 7. Interrupt therapy if ferritin falls below 500 μg/L 7.

Important Pitfalls to Avoid

• Rapid iron mobilization in cardiac patients: Those with arrhythmias or cardiomyopathy require careful monitoring due to increased risk of sudden death with rapid iron mobilization 5
• Vitamin C supplements: Absolutely avoid, especially before iron depletion, as they accelerate iron mobilization to dangerous levels 1, 2, 5
• Raw shellfish: Avoid due to risk of Vibrio vulnificus infection in iron-overloaded patients 1
• Alcohol: Should be minimized or completely avoided in patients with cirrhosis 2, 4
• Ignoring anemia: May indicate another underlying condition requiring investigation 2

Prognosis

The average survival is less than one year in untreated patients with severe cardiac impairment 3. However, if treated early and aggressively, survival approaches that of the general heart failure population 3. Cardiac function can normalize within one year with appropriate iron chelation therapy 8.