What cardiac complications arise in transfusion‑dependent beta thalassemia and what are the recommended prevention and management strategies?

Cardiac Complications in Beta Thalassemia Major

Heart failure from cardiac iron overload is the leading cause of death in transfusion-dependent beta thalassemia major, accounting for approximately 70% of mortality, and requires aggressive prevention through lifelong iron chelation therapy combined with regular cardiac monitoring. 1

Primary Cardiac Complications

Iron-mediated cardiomyopathy is the dominant cardiac complication in beta thalassemia major, resulting from:

• Myocardial siderosis: Excess iron accumulates in cardiac myocytes when iron levels exceed transferrin binding capacity, entering cells through L-type calcium channels and causing direct myocardial toxicity 2
• Dilated cardiomyopathy: Progressive ventricular dysfunction develops from chronic iron deposition, leading to reduced ejection fraction and heart failure 3, 4
• Arrhythmias: Life-threatening cardiac rhythm disturbances occur in up to 71% of beta thalassemia major patients, including atrial fibrillation and ventricular arrhythmias 3

High-output cardiac state contributes independently to cardiac dysfunction:

• Chronic anemia drives compensatory increases in cardiac output, leading to left ventricular hypertrophy and structural remodeling even in the absence of iron overload 5
• This mechanism is particularly important in thalassemia intermedia but also contributes to cardiac stress in transfusion-dependent patients 4

Prevention Strategies

Transfusion Protocol

Maintain pre-transfusion hemoglobin at 9-10 g/dL and post-transfusion hemoglobin at 13-14 g/dL through regular transfusions every 3-4 weeks to suppress ineffective erythropoiesis and reduce cardiac output stress 1, 6

Iron Chelation Therapy

Begin iron chelation immediately when regular transfusions are established, as each transfused unit delivers 200-250 mg of elemental iron with no physiological excretion mechanism 6, 2

First-line chelation options:

• Deferiprone 75 mg/kg/day (oral): Superior efficacy for cardiac iron removal compared to deferoxamine 6, 7
• Deferoxamine 50 mg/kg/day (subcutaneous): 5-7 nights per week via continuous infusion, less effective for cardiac iron but widely used 6, 7
• Deferasirox 20-40 mg/kg/day (oral): Comparable efficacy to deferoxamine for overall iron overload 6

Combination therapy (deferiprone + deferoxamine) is more effective than monotherapy for reducing cardiac iron burden and should be used in patients with significant cardiac involvement 6, 7

Cardiac Monitoring Protocol

Annual cardiac MRI T2 imaging* is the gold standard for detecting cardiac iron before symptoms develop 1, 6:

• *T2 <10 ms**: Severe cardiac iron overload with 47% risk of heart failure within 1 year (270-fold increased risk compared to T2* >10 ms) 7, 8
• T2 10-20 ms*: Mild to moderate cardiac iron loading requiring intensified chelation 1
• T2 >20 ms*: Adequate cardiac iron control 9

Critical caveat: Serum ferritin and liver iron concentration are NOT adequate surrogates for cardiac iron measurement and should not be used alone to guide cardiac risk assessment 1, 8

Annual echocardiography to assess left ventricular ejection fraction, recognizing that interpretation is complicated by the high-output state in chronically anemic patients (baseline tachycardia, enlarged end-diastolic volume, high ejection fraction) 1, 6

Monitor serum ferritin every 3 months as a trend marker only, not as a predictor of cardiac iron 6, 7

Management of Acute Cardiac Decompensation

Acute heart failure is a medical emergency requiring immediate transfer to a specialized thalassemia center 1

Initiate urgent combination chelation therapy:

• Continuous intravenous deferoxamine 50 mg/kg/day PLUS oral deferiprone 75 mg/kg/day 6, 7
• This combination is more effective than monotherapy and must be started immediately to control free iron toxicity 6
• Avoid deferasirox in acute heart failure due to concerns about renal perfusion 7

Maintain higher pre-transfusion hemoglobin targets to reduce cardiac output stress during acute decompensation 4

Important pitfall: Cardiac iron removal is extremely slow, requiring several years of intensive chelation even after resolution of acute heart failure, and premature termination of intensive therapy leads to high relapse rates 1, 7

Prevalence and Prognosis

• Cardiac iron overload (T2 <20 ms)* affects 25% of transfusion-dependent thalassemia patients worldwide 9
• Cardiac complications overall occur in 42% of patients 9
• Severe cardiac iron loading (T2 <10 ms)* is present in 37% of adult patients and is strongly associated with cardiac events 8

With optimal adherence to transfusions and chelation, patients can expect survival into their 40s-50s, compared to death by age 10 without treatment 6

Additional Preventive Measures

• Hepatitis B vaccination before starting transfusions with regular screening for hepatitis B and C 6
• Limit red meat consumption to reduce heme iron intake 6
• Never take iron supplements or multivitamins containing iron 6
• Hematopoietic stem cell transplantation is the only curative option and should be performed as early as possible, ideally before age 14 years and before iron-related organ damage develops 6