What is the treatment for hyperferritinemia in patients with a pacemaker?

Treatment of Hyperferritinemia in Patients with Pacemakers

Therapeutic phlebotomy is the first-line treatment for hyperferritinemia in patients with pacemakers, with a target ferritin level below 20 ng/ml for initial therapy, followed by maintenance phlebotomy 3-4 times yearly for men and 1-2 times yearly for women. 1

Diagnostic Approach

Before initiating treatment, it's essential to determine the cause of hyperferritinemia:

• Evaluate serum ferritin and transferrin saturation as the first diagnostic step to identify the cause of hyperferritinemia 2
• Rule out common causes of hyperferritinemia including:
  • Chronic alcohol consumption
  • Inflammation (check CRP)
  • Cell necrosis (check AST, ALT, CK)
  • Malignancy
  • Non-alcoholic fatty liver disease and metabolic syndrome 1
• Consider liver MRI to assess iron concentration non-invasively, which is particularly important in patients with pacemakers where standard MRI protocols may be contraindicated 2
• Determine if hyperferritinemia is associated with iron overload (hemochromatosis) or is dysmetabolic (normal transferrin saturation) 3, 4

Treatment Options

1. Phlebotomy Therapy

• For hereditary hemochromatosis and other iron overload conditions:
  • Initial therapy: Remove 400-500 cc of blood (200-250 mg of iron) weekly or twice weekly until target ferritin below 20 ng/ml is achieved 1
  • Maintenance therapy: 3-4 phlebotomies yearly for men, 1-2 yearly for women 1
  • Monitor hemoglobin, ferritin, and hematocrit during maintenance therapy 1
  • Phlebotomy has shown improvements in cardiac function in hemochromatosis patients with cardiomyopathy 1

2. Chelation Therapy

For patients with significant anemia, malignancy, or hemodynamic instability where phlebotomy is contraindicated:

• Deferoxamine: High-affinity iron chelator that binds with ferric ion and removes cardiac iron 1
  • Can be administered intravenously for rapid removal of cardiac iron in heavily iron-loaded patients 1
  • Has shown improvements in left ventricular ejection fraction (52% to 63%) and reductions in LV volume and mass index 1
• Deferiprone: Oral chelator that has been associated with reduced cardiac mortality 1
• Deferasirox: Oral chelator option 1
• Combination therapy: Deferoxamine with deferiprone has shown benefit in patients with cardiac siderosis with abnormal or falling LVEF 1

3. Special Considerations for Patients with Pacemakers

• Cardiac monitoring is essential, with annual electrocardiography and echocardiography to assess chamber dimension and function 1
• Patients with pacemakers should receive physiological pacing (DDD system) to maintain adequate chronotropic response and atrial-ventricular coordination 1
• Right ventricular pacing may induce dyssynchrony and worsen symptoms in heart failure patients 1
• For patients with both hyperferritinemia and atrial fibrillation requiring rate control:
  • Beta-blockers, diltiazem, verapamil, or digoxin are recommended for patients with LVEF >40% 1
  • Beta-blockers and/or digoxin are recommended for patients with LVEF ≤40% 1

4. Dietary Management

• Dietary interventions alone are insufficient to treat significant iron overload but may provide adjunctive benefit 1
• Recommendations include:
  • Minimize alcohol consumption as it increases iron absorption 1
  • Avoid multivitamin tablets containing iron and vitamin C 1
  • Consider foods containing tannates, phytates, oxalates, calcium, and phosphates which can bind iron and inhibit absorption 1

Monitoring and Follow-up

• Monitor ferritin levels at least every 3 months 1
• For patients with cardiac involvement, perform annual cardiac assessment including:
  • Clinical cardiac evaluation (history, physical examination) 1
  • Electrocardiography 1
  • Echocardiography to assess chamber dimensions and function 1
• For patients with pacemakers, ensure regular device checks to confirm proper functioning and optimize programming 1

Treatment Algorithm

1. Determine if hyperferritinemia is associated with iron overload (elevated transferrin saturation) or is dysmetabolic (normal transferrin saturation)
2. For iron overload with normal cardiac function:
   • Initiate weekly phlebotomy if hemodynamically stable
   • Consider chelation therapy if anemic or hemodynamically unstable
3. For iron overload with cardiac dysfunction:
   • Consider combination therapy with deferoxamine and deferiprone
   • Optimize pacemaker settings to ensure physiological pacing
4. For dysmetabolic hyperferritinemia:
   • Address underlying metabolic disorders
   • Consider less aggressive phlebotomy schedule
5. Monitor ferritin levels every 3 months and adjust therapy accordingly