Can iron deficiency lead to heart failure and low stroke volume index in patients with pre-existing heart conditions?

Iron Deficiency and Cardiac Effects: Heart Failure and Stroke Volume

Iron deficiency is a major contributor to heart failure development and progression, affecting 40-70% of chronic heart failure patients, and it directly impairs cardiac function including stroke volume through multiple mechanisms, independent of anemia. 1

Direct Cardiac Effects of Iron Deficiency

Myocardial Dysfunction and Remodeling

• Iron deficiency causes left ventricular hypertrophy, left ventricular dilation, and symptomatic heart failure through chronic sympathetic activation and increased cardiac workload 2
• These structural changes occur even before anemia develops, demonstrating that iron deficiency itself—not just reduced hemoglobin—directly damages the heart 3
• Iron is essential for mitochondrial function in cardiac myocytes; deficiency impairs cellular energy production, compromising contractility and cardiac output 3

Impact on Stroke Volume

• Iron deficiency creates a chronic high-output state where the heart must pump more blood to compensate for reduced oxygen-carrying capacity 1
• This volume overload increases end-diastolic volume and stroke volume initially, but eventually leads to cardiac decompensation 1
• As heart failure progresses, stroke volume index ultimately decreases due to myocardial dysfunction and impaired contractility 2

Progression to Heart Failure

Pathophysiologic Mechanisms

• Absolute iron deficiency depletes total body iron stores through malabsorption, malnutrition, and gastrointestinal blood loss (often exacerbated by anticoagulants and antithrombotics) 1
• Functional iron deficiency occurs when chronic inflammation elevates hepcidin, blocking iron absorption and mobilization from storage sites despite adequate total body iron 1, 4
• Both types of iron deficiency impair skeletal muscle, cardiac muscle, renal function, and immune system function, creating a vicious cycle that worsens heart failure 3

Clinical Consequences

• Iron deficiency is independently associated with worse heart failure symptoms, reduced exercise capacity, and poorer prognosis regardless of anemia status 5, 6
• It increases hospitalization risk and mortality in heart failure patients 5, 7
• The prevalence reaches 50-70% in stable heart failure patients, making it one of the most common and important comorbidities 6, 3

Clinical Implications and Screening

Who to Screen

• All newly diagnosed heart failure patients should have iron status evaluated as part of initial workup (Class I recommendation, ESC guidelines) 1
• Existing heart failure patients who remain symptomatic despite optimal medical therapy should be screened 1, 5
• Re-evaluate iron status 1-2 times per year and after any heart failure hospitalization 1, 5

Diagnostic Criteria

• Iron deficiency in heart failure is defined as either:
  • Ferritin <100 μg/L (absolute deficiency), OR
  • Ferritin 100-299 μg/L with transferrin saturation <20% (functional deficiency) 1
• Both ferritin and transferrin saturation must be measured simultaneously 1
• Note: Serum ferritin <100 μg/L may not identify patients most likely to respond to treatment; transferrin saturation <20% is a better predictor of treatment response 7

Treatment and Outcomes

Evidence-Based Recommendations

• Intravenous iron (ferric carboxymaltose or ferric derisomaltose) is recommended for NYHA class II-III heart failure with reduced ejection fraction (HFrEF) and iron deficiency to improve functional capacity, quality of life, and reduce hospitalizations 5, 7
• IV iron is superior to oral iron preparations in heart failure patients due to better absorption and efficacy 6
• Treatment improves NYHA functional class, 6-minute walk test distance, peak oxygen consumption, and quality of life 1, 6

Important Caveats

• Do not administer IV iron if hemoglobin >15 g/dL due to unknown safety profile 1, 5
• Screen for treatable causes of iron deficiency (especially gastrointestinal bleeding) before initiating therapy 5
• The benefit of treating iron deficiency in heart failure with preserved ejection fraction (HFpEF) remains unknown 5
• Long-term safety data for IV iron in heart failure are still being established 5

Dosing Strategy

• Calculate total iron need based on hemoglobin and body weight 1
• Administer ferric carboxymaltose in single doses of 500-1000 mg iron 1
• Recheck ferritin and transferrin saturation after 3 months, then 1-2 times yearly 1

Critical Clinical Pitfall

Despite strong guideline recommendations, iron deficiency remains severely under-diagnosed and under-treated in heart failure practice, denying many patients therapy that could significantly improve their cardiovascular function and quality of life. 1, 6 This represents a major gap between evidence and clinical practice that must be addressed through systematic screening protocols.