I have bilateral lower‑extremity edema with a positive Stemmer sign, concentric left‑ventricular hypertrophy, normal left‑ventricular filling pressures (E/e′ ≈ 8), a low brain‑type natriuretic peptide level, and a low stroke‑volume index on 2‑D echocardiography; I am taking eplerenone 25 mg daily. Is eplerenone contraindicated, and are BNP/NT‑proBNP and the low stroke‑volume index reliable for assessing heart failure in this setting?

Eplerenone Use in Your Clinical Context

Eplerenone 25 mg daily is NOT contraindicated in your case based on the information provided, assuming your serum potassium is ≤5.5 mEq/L and your creatinine clearance is >30 mL/min. 1

Eplerenone Contraindications Assessment

Your clinical scenario requires careful evaluation against FDA-specified contraindications:

Absolute contraindications for ALL patients include: 1

• Serum potassium >5.5 mEq/L at initiation
• Creatinine clearance ≤30 mL/min
• Concomitant strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir)

Additional contraindications specific to hypertension treatment (NOT heart failure): 1

• Type 2 diabetes with microalbuminuria
• Serum creatinine >2.0 mg/dL (males) or >1.8 mg/dL (females)
• Creatinine clearance <50 mL/min
• Concomitant potassium supplements or potassium-sparing diuretics

Critical distinction: The stricter contraindications apply only when eplerenone is used for hypertension treatment. For heart failure with reduced ejection fraction post-MI, the threshold is more permissive (creatinine clearance >30 mL/min vs. >50 mL/min). 1

Your situation: You have concentric LV hypertrophy with normal filling pressures (E/e′ ≈ 8), which does NOT represent HFrEF post-MI—the FDA-approved indication for eplerenone in heart failure. 1 If eplerenone is being used for hypertension management in your case, the stricter contraindications apply. 1

BNP/NT-proBNP Reliability in Your Clinical Context

Your concern about BNP unreliability in grade 1 diastolic dysfunction is well-founded and supported by evidence.

Why BNP May Be Unreliable in Your Case

Normal E/e′ ratio (≈8) indicates normal LV filling pressures: 2

• E/e′ <8 is considered normal
• Your value of approximately 8 sits at the threshold, suggesting minimal elevation of filling pressures
• BNP levels correlate with ventricular wall stress and filling pressures 3, 4

BNP is significantly lower in HFpEF compared to HFrEF: 3, 4

• Patients with preserved ejection fraction and diastolic dysfunction typically have lower BNP levels than those with systolic dysfunction
• Even with elevated filling pressures, HFpEF patients may have BNP in the "gray zone" (100-400 pg/mL) 2, 3

Grade 1 diastolic dysfunction with normal filling pressures produces minimal BNP elevation: 2, 5

• BNP reflects current hemodynamic stress, not structural abnormalities alone
• With E/e′ ≈ 8, your filling pressures are not significantly elevated, which would result in low-normal BNP
• A study specifically examining patients with BNP 100-400 pg/mL and normal LVEF found that BNP was NOT predictive of heart failure (P = 0.78), while E/e′ ratio WAS predictive (P = 0.0032) 5

Flash pulmonary edema demonstrates BNP can be deceptively low initially: 6

• In first-time flash pulmonary edema with preserved LVEF, BNP levels were significantly lower (median 535 pg/mL) despite similarly elevated filling pressures compared to reduced LVEF patients 6
• This demonstrates that preserved systolic function with diastolic dysfunction can present with lower BNP despite significant hemodynamic derangement 6

NT-proBNP Would Be More Reliable

NT-proBNP is preferred over BNP for several reasons: 2, 3

• Longer half-life provides more stable measurements
• Less affected by acute hemodynamic changes
• Better studied in HFpEF populations
• Diagnostic threshold in non-acute setting: >125 pg/mL suggests cardiac dysfunction 2

However, even NT-proBNP has limitations in your scenario: 3

• With normal filling pressures (E/e′ ≈ 8), NT-proBNP may remain in normal or low-normal range
• The absence of elevated natriuretic peptides does NOT exclude diastolic dysfunction when filling pressures are not significantly elevated 2, 5

Stroke Volume Index Assessment

Your concern about SVI underestimation from LVOT mismeasurement is clinically astute and represents a common pitfall in 2D echocardiography.

LVOT Measurement Limitations

LVOT diameter measurement is a critical source of error:

• Small measurement errors are squared in the calculation (SV = π × [LVOT diameter/2]² × VTI)
• A 1 mm error in LVOT diameter measurement translates to approximately 10% error in stroke volume calculation
• 2D echocardiography measures LVOT in a single plane, potentially missing the true maximum diameter

Alternative SV Calculation: EDV - ESV

The volumetric method (SV = EDV - ESV) is theoretically more accurate but has its own limitations:

Advantages:

• Does not rely on geometric assumptions about LVOT shape
• Directly measures ventricular volumes using Simpson's biplane method
• Less dependent on single linear measurements

Limitations and sources of error:

• Requires excellent endocardial border definition
• Assumes accurate tracing of LV cavity in two orthogonal planes
• Foreshortened apical views underestimate volumes
• Trabeculations and papillary muscles can be inconsistently included/excluded
• Image quality significantly affects accuracy

Recommendation for your situation:

• Compare both methods (LVOT-based and volumetric)
• If they diverge significantly (>15-20%), the measurements are unreliable
• Consider 3D echocardiography if available, which provides more accurate volumetric assessment without geometric assumptions
• Cardiac MRI is the gold standard for ventricular volumes and stroke volume if discrepancies persist and clinical decision-making is affected

Clinical Context for Low SVI

Your bilateral lower-extremity edema with positive Stemmer sign suggests lymphedema rather than cardiac edema: 7

• Stemmer sign (inability to pinch skin at base of second toe) is pathognomonic for lymphedema
• Cardiac edema typically does NOT produce positive Stemmer sign 7
• This finding argues AGAINST heart failure as the primary cause of your edema

Low SVI in the context of normal E/e′ and low BNP:

• If truly low, consider measurement error first (as you are doing)
• Concentric LV hypertrophy reduces cavity size, which can result in lower absolute stroke volume even with normal ejection fraction
• Low SVI with normal filling pressures does not necessarily indicate heart failure
• Consider indexing to body surface area (stroke volume index) for more accurate assessment

Practical Algorithm for Your Situation

1. Verify eplerenone is not contraindicated: Check serum potassium (<5.5 mEq/L) and creatinine clearance (>30 mL/min if used for any indication; >50 mL/min if used specifically for hypertension) 1

2. Interpret low BNP cautiously: With E/e′ ≈ 8 and concentric LVH without reduced EF, low BNP does NOT exclude diastolic dysfunction but does suggest filling pressures are not significantly elevated at rest 2, 5, 6

3. Pursue NT-proBNP when available: More reliable than BNP for chronic assessment, though still may be low-normal with grade 1 diastolic dysfunction 2, 3

4. Resolve SVI discrepancy: Compare LVOT-based and volumetric methods; if discordant, consider 3D echo or cardiac MRI for definitive assessment

5. Recognize lymphedema as likely cause of edema: Positive Stemmer sign strongly suggests lymphedema rather than cardiac cause 7