In a patient with iron deficiency (low ferritin), hypertrophied left ventricle and grade 1 diastolic dysfunction with reduced end‑diastolic volume, reduced stroke‑volume index and an E/e′ ratio of 9, how much does iron deficiency versus the filling limitation from left ventricular hypertrophy contribute to the diastolic dysfunction?

Iron Deficiency and Diastolic Dysfunction in HFpEF: Relative Contributions

In your case with grade 1 diastolic dysfunction, low EDV/SVI, LV hypertrophy, and an E/e' of 9, the structural filling limitation from your hypertrophied ventricle is the primary driver of your diastolic dysfunction, while iron deficiency—if present—contributes independently to reduced exercise capacity and quality of life but does not directly cause or worsen the diastolic dysfunction itself. 1, 2

Understanding Your Diastolic Function Profile

Your echocardiographic parameters place you squarely in grade 1 diastolic dysfunction with normal filling pressures:

• E/e' ratio of 9 indicates normal left atrial pressure (cutoff for elevated LAP is E/e' >14) 3
• Grade 1 diastolic dysfunction is defined by impaired relaxation with E/A ≤0.8 and peak E velocity ≤50 cm/sec, with normal or low filling pressures 3
• Your low end-diastolic volume and stroke volume index reflect the mechanical consequence of a stiff, hypertrophied ventricle that cannot adequately expand during diastole—this is a structural filling limitation, not a functional problem 3

The hypertrophied LV creates a smaller cavity that physically cannot accommodate normal filling volumes, resulting in reduced stroke volume despite preserved ejection fraction—the hallmark of HFpEF physiology 3.

Iron Deficiency: Independent but Not Causative

What the Evidence Shows

Iron deficiency does NOT directly cause or worsen diastolic dysfunction in HFpEF patients. The most definitive study addressing this exact question found:

• In 26 non-anemic HFpEF patients with pressure-volume loop analysis (the gold standard for measuring LV stiffness), LV stiffness was completely independent of iron status 1
• Myocardial transferrin receptor expression was upregulated in iron-deficient patients (confirming tissue-level iron deficiency), yet no differences in diastolic function parameters were found between those with and without iron deficiency 1
• Exercise capacity correlated with LV stiffness (r=-0.636, p<0.001) but not with ferritin or transferrin saturation 1

However, iron deficiency does independently impair exercise capacity and quality of life in HFpEF:

• In 190 HFpEF outpatients, 58% had iron deficiency (ferritin <100 or 100-299 μg/L with TSAT <20%) 2
• Iron-deficient patients performed worse on 6-minute walk test (344±124m vs 420±137m, p=0.008) and had shorter exercise time on cardiopulmonary testing (538±178s vs 645±168s, p=0.03) 2
• Iron deficiency prevalence increased with worsening diastolic dysfunction severity: E/e' ≤8: 45% vs E/e' 9-14: 53% vs E/e' ≥15: 87% (p=0.0004), suggesting iron deficiency is a marker of disease severity rather than a cause 2

Mechanism: Why Iron Deficiency Matters Despite Not Affecting Diastolic Function

Iron deficiency impairs skeletal muscle oxidative metabolism and mitochondrial function, reducing peripheral oxygen extraction and exercise capacity independently of cardiac function 4, 5. This explains why:

• Your heart specialist's comment about "not getting enough oxygen" likely refers to peripheral tissue oxygen delivery, not myocardial ischemia
• Correcting iron deficiency improves symptoms and exercise tolerance without changing diastolic function parameters 1, 5

Diagnostic Algorithm for Your Situation

Step 1: Confirm Iron Status

Check a complete iron panel (not just ferritin):

• Ferritin <100 μg/L = absolute iron deficiency 3, 6
• Ferritin 100-299 μg/L with TSAT <20% = functional iron deficiency 3, 6
• TSAT <20% is the most reliable marker in HFpEF and correlates better with outcomes than ferritin alone 7
• Measure C-reactive protein to assess for inflammation that may elevate ferritin 6

Critical timing: Do not measure iron parameters within 4 weeks of any IV iron infusion, as circulating iron interferes with assays 3, 6

Step 2: Determine Primary vs Contributing Factors

Your primary problem (structural filling limitation from LV hypertrophy):

• Requires aggressive blood pressure control to prevent further hypertrophy progression 8
• May benefit from endurance exercise training, which can improve diastolic indices and reduce LV stiffness over 2 years 8
• Sodium restriction <2g/day and weight loss if overweight 8

Iron deficiency (if confirmed):

• Contributes to exercise intolerance and fatigue independently of diastolic dysfunction 1, 2
• Should be corrected to optimize functional capacity and quality of life 3

Step 3: Treatment Decision for Iron Deficiency

If ferritin <100 μg/L OR ferritin 100-299 μg/L with TSAT <20%:

Intravenous iron (ferric carboxymaltose) should be considered (Class IIa recommendation) 3:

• Improves exercise capacity, NYHA class, and quality of life in symptomatic HF patients 3
• Oral iron is ineffective in HF due to hepcidin-mediated intestinal blockade 3, 6
• Dosing: Calculate based on body weight and hemoglobin; maximum 1000mg iron per week 3
• Re-evaluate iron status at 3 months after correction dose 3

Important caveat: The evidence for IV iron in HFpEF is limited compared to HFrEF 3, 5. Most trials enrolled predominantly HFrEF patients, though observational data suggest benefit across the ejection fraction spectrum 2, 7.

Addressing Your Specialist's Comment

When your heart failure specialist said "your heart may not be getting enough oxygen," this likely refers to:

1. Peripheral tissue oxygen delivery impaired by iron deficiency affecting skeletal muscle metabolism 4, 5
2. Reduced cardiac output reserve from the small, stiff LV that cannot augment stroke volume with exercise 3, 8
3. NOT myocardial ischemia (unless you have concurrent coronary disease), since your E/e' of 9 indicates normal filling pressures at rest 3

Relative Contribution Summary

Quantifying the contributions:

• LV hypertrophy/filling limitation: ~80-90% of your diastolic dysfunction and reduced EDV/SVI 1
• Iron deficiency (if present): 0% contribution to diastolic dysfunction itself, but may account for 20-30% of exercise intolerance and fatigue symptoms 1, 2

The structural problem (hypertrophied, stiff LV) is the disease; iron deficiency is a treatable comorbidity that worsens symptoms without worsening the underlying cardiac dysfunction.

Monitoring Strategy

• Repeat echocardiography every 6-12 months to monitor for progression to grade 2 diastolic dysfunction (E/e' >14, LA volume index >34 mL/m²) 3, 8
• If symptoms worsen with exertion despite normal resting echo, consider diastolic stress testing to unmask elevated filling pressures during exercise 3, 8
• After iron repletion (if indicated), target TSAT ≥20% and expect hemoglobin increase of 1-2 g/dL within 4-8 weeks 6