What is the management for a patient with tachycardia and elevated ferritin levels?

Management of Tachycardia with Elevated Ferritin

The immediate priority is to determine whether the elevated ferritin represents true iron overload (requiring urgent assessment for cardiac hemochromatosis) or is a nonspecific acute phase reactant from inflammation, infection, or other causes—this distinction is made by measuring transferrin saturation (TS), which if >45% suggests iron overload requiring further evaluation, while normal TS points to secondary hyperferritinemia. 1

Initial Diagnostic Approach

Measure Transferrin Saturation Immediately

• Calculate TS from serum iron divided by total iron-binding capacity (TIBC) 1
• TS >45% indicates possible iron overload and warrants urgent further evaluation 1
• TS <45% with elevated ferritin suggests ferritin elevation is from inflammation, not iron overload 1

Interpret the Ferritin-TS Combination

• Elevated ferritin with elevated TS (>45%): Proceed to iron overload evaluation 1
• Elevated ferritin with normal/low TS (<20%): Consider secondary causes of hyperferritinemia including inflammation, chronic liver disease, malignancy, infection, or rheumatologic conditions 1, 2, 3
• Ferritin is an acute phase protein and commonly elevated in necroinflammatory liver disease (alcoholic liver disease, chronic hepatitis B/C, NAFLD), lymphomas, and chronic inflammatory conditions 1

If Iron Overload is Confirmed (TS >45%)

Urgent Cardiac Assessment for Iron Overload Cardiomyopathy

Cardiac hemochromatosis is a medical emergency that causes rapid deterioration once heart failure develops, and tachycardia may be an early manifestation of cardiac involvement. 4

Specific Cardiac Manifestations to Assess:

• Arrhythmias: Atrial arrhythmias (intra-atrial reentrant tachycardia, atrial fibrillation, ectopic atrial tachycardia) are most common with cardiac iron loading 1
• Ventricular arrhythmias (couplets, nonsustained VT) are more specific for iron cardiotoxicity 1
• Dilated cardiomyopathy with reduced ejection fraction and fractional shortening 4
• Congestive heart failure symptoms: progressive dyspnea, fluid retention, abdominal pain from hepatic congestion 1

Obtain These Cardiac Studies:

• Electrocardiogram: Look for arrhythmias, conduction abnormalities 1
• Echocardiography: Assess chamber dimensions, ejection fraction, and cardiac function 1
• Cardiac MRI with T2*: This is superior to other tests for quantitatively assessing myocardial iron load 4
  • Cardiac T2* <10 ms predicts heart failure development 1
  • Cardiac T2* <6 ms indicates 50% likelihood of developing heart failure within 12 months without treatment intensification 1
• BNP level: Elevated in heart failure but may be a late sign 1

Confirm Iron Overload Diagnosis

HFE Genetic Testing

• Test for C282Y and H63D mutations 1, 3
• C282Y homozygotes with TS >45% (>50% in males/postmenopausal women) and ferritin >200 μg/L (females) or >300 μg/L (males) confirms hereditary hemochromatosis 1

Assess Hepatic Iron Load

• Liver MRI for quantitative hepatic iron concentration or liver biopsy if concurrent liver disease 1, 3
• Ferritin >1000 μg/L warrants liver biopsy to assess for cirrhosis in symptomatic patients 1

Treatment Based on Findings

If Cardiac Iron Overload WITHOUT Severe Heart Failure

Therapeutic phlebotomy is the gold standard treatment for nonanemic patients with cardiac hemochromatosis. 1, 4

Phlebotomy Protocol:

• Induction phase: Remove 400-500 mL blood (200-250 mg iron) weekly or twice weekly 1
• Target ferritin <50 μg/L during induction, then maintain <100 μg/L 1
• Historical targets were ferritin <20 ng/mL, but current guidelines recommend <50 μg/L induction and <100 μg/L maintenance 1
• Monitor hemoglobin, ferritin, and hematocrit during treatment 1
• Improvements in cardiac function and arrhythmias occur with aggressive iron removal, especially when started early 1

Maintenance Phlebotomy:

• Men typically require 3-4 phlebotomies per year 1
• Women typically require 1-2 phlebotomies per year 1

If Cardiac Iron Overload WITH Severe Heart Failure or Anemia

This is a medical emergency requiring specialized care at a center experienced in iron overload cardiomyopathy. 1

Intensive Chelation Therapy:

• Continuous intravenous deferoxamine is the treatment of choice when phlebotomy is contraindicated 1
• Deferoxamine improved survival from 6 of 7 patients in one series, and 17 of 20 patients in another 1
• High-dose IV deferoxamine for rapid cardiac iron removal in heavily loaded patients with cardiac failure 1
• Combination therapy with deferoxamine plus deferiprone is recommended for patients with cardiac siderosis and abnormal/falling LVEF 1

Arrhythmia Management:

• Amiodarone is often successful for controlling atrial arrhythmias during intensive iron chelation 1
• Can often be discontinued after 6-12 months once cardiac iron is removed 1
• Avoid ablation until successful cardiac iron removal is documented by MRI 1
• Avoid implantable devices if possible as they preclude further cardiac iron monitoring by MRI; consider defibrillation vest as bridge during intensive chelation 1

Standard Heart Failure Therapy:

• ACE inhibitors, beta-blockers, and minimal diuretics (to maintain preload) 1

If Secondary Hyperferritinemia (Normal TS)

• Treat underlying cause: inflammation, infection, liver disease, malignancy 1, 3
• Tachycardia management based on underlying etiology
• No iron removal therapy indicated 1

Critical Pitfalls to Avoid

• Do not dismiss elevated ferritin as "just inflammation" without checking TS—iron overload is missed in 80% of cases when complete iron evaluation is not performed 1
• Do not delay cardiac assessment if TS is elevated—cardiac hemochromatosis deteriorates rapidly once heart failure develops 4
• Do not use ferritin alone to exclude iron overload—in the general population, iron overload is not the most common cause of elevated ferritin 1
• Do not perform aggressive diuresis in iron overload cardiomyopathy—maintaining preload is critical 1
• Single ferritin measurements can be misleading—trends over time are more valuable 1