What are the key differences in symptoms and treatment approaches for an adult patient with a history of cardiovascular disease or anemia, presenting with fatigue, shortness of breath, or dizziness, suspected to have either low stroke volume index or iron deficiency?

Distinguishing Low Stroke Volume Index from Iron Deficiency

Both conditions share nearly identical symptoms—fatigue, dyspnea, lightheadedness, and exercise intolerance—making symptom-based differentiation unreliable; therefore, diagnosis depends entirely on objective testing with serum ferritin, transferrin saturation, and echocardiography. 1

Overlapping Clinical Presentation

The symptom profiles are essentially indistinguishable because both conditions cause inadequate oxygen delivery to tissues:

• Fatigue and exercise intolerance occur in both conditions and represent the most unreliable differentiating features 1
• Dyspnea and lightheadedness result from either reduced cardiac output (low stroke volume) or reduced oxygen-carrying capacity (iron deficiency) 1
• Additional shared symptoms include palpitations, dizziness, chest discomfort, and presyncope 2

In iron deficiency specifically, patients may also experience:

• Restless legs syndrome (32-40% of cases) 3
• Pica (40-50% of cases), particularly ice craving (pagophagia) 2, 3
• Specific physical findings such as angular stomatitis, glossitis, koilonychia, and blue sclerae 2

Diagnostic Algorithm

Iron Deficiency Assessment

Serum ferritin is the single most powerful diagnostic test: 1

• <30 ng/mL indicates iron deficiency in non-inflammatory states 3
• <100 ng/mL suggests deficiency when inflammation is present 2, 1
• Ferritin 100-300 ng/mL with transferrin saturation <20% also indicates iron deficiency 2

Critical pitfall: Ferritin is an acute-phase reactant and may be falsely elevated in inflammatory conditions, making it unreliable as a sole marker when C-reactive protein is elevated 4

Transferrin saturation <20% indicates inadequate iron delivery to bone marrow, even when ferritin appears normal 5, 1

Cardiac Assessment

Echocardiography with Doppler is required to measure stroke volume index, assess valve function, and evaluate cardiac output 1

Recommended Laboratory Panel

For patients presenting with fatigue, dyspnea, or dizziness: 4

• Complete blood count with differential
• Serum ferritin
• Serum iron and transferrin saturation
• C-reactive protein (to interpret ferritin accurately)
• Comprehensive metabolic panel
• Thyroid function tests

Key Distinguishing Features

Iron Deficiency Specific Findings

• Microcytic anemia (though iron deficiency can exist without anemia) 6, 3
• Transferrin saturation <20% 5, 1
• Low ferritin (with caveats regarding inflammation) 1, 3
• Thrombocytosis may occur and paradoxically increases cardiovascular risk 7

Low Stroke Volume Index Specific Findings

• Reduced cardiac output on echocardiography 1
• Structural cardiac abnormalities (valvular disease, cardiomyopathy) 2
• Elevated natriuretic peptides in heart failure 7

Critical Clinical Considerations

Both Conditions Frequently Coexist

• 37-61% of heart failure patients have iron deficiency 8, 3
• Iron deficiency independently worsens cardiac function and increases hospitalization risk 2, 8
• Iron deficiency in heart failure is uniquely associated with reduced exercise capacity, independent of anemia status 2

Special Population: Cardiovascular Disease Patients

Iron deficiency in cardiac patients carries additional risks: 1

• Increased stroke risk 1, 6
• Increased myocardial ischemia risk 1
• In cyanotic heart disease, iron deficiency reduces oxygen-carrying capacity without lowering viscosity, mimicking hyperviscosity symptoms 5

Treatment Implications

When Iron Deficiency is Confirmed

Intravenous iron is superior to oral supplementation in heart failure patients: 2

• Oral iron failed to improve outcomes in IRONOUT-HF trial 2, 9
• IV ferric carboxymaltose improved NYHA class, 6-minute walk test, and quality of life in FAIR-HF and CONFIRM-HF trials 2, 9
• Benefits occur independent of anemia presence 2

Treatment targets: 5

• Transferrin saturation >20%
• Ferritin >100 ng/mL (>200 ng/mL in hemodialysis patients)

When Low Stroke Volume Index is Confirmed

• Severe aortic stenosis with low stroke volume and symptoms warrants valve replacement 1
• Optimize guideline-directed medical therapy for heart failure 2

When Both Conditions Coexist

Treat iron deficiency first or concurrently, as correction may improve cardiac function and symptoms: 1

• Iron repletion can reduce natriuretic peptides 7
• Improved oxygen-carrying capacity may enhance cardiac performance 7
• ESC guidelines recommend testing all heart failure patients for iron deficiency (Class IC indication) 9

Common Pitfalls to Avoid

• Do not rely on symptoms alone to differentiate these conditions 1
• Do not use ferritin as the sole diagnostic marker when inflammation is present 4
• Do not assume normal hemoglobin excludes iron deficiency—non-anemic iron deficiency is common and clinically significant 2, 3
• Do not use oral iron in heart failure patients—absorption is impaired and efficacy is poor 2, 9
• Do not perform routine phlebotomy in cyanotic heart disease with iron deficiency, as this paradoxically increases complications 5