Can heart failure with preserved ejection fraction (HFpEF) present with a normal left ventricular end‑diastolic pressure (LVEDP) at rest in older women with hypertension, obesity, diabetes, chronic kidney disease, or atrial fibrillation?

Can HFpEF Present with Normal LVEDP at Rest?

Yes, HFpEF can absolutely present with normal left ventricular end-diastolic pressure (LVEDP) at rest, particularly in earlier stages of the disease—this is a critical diagnostic pitfall that clinicians must recognize. Approximately 35% of HFpEF patients present with "unexplained" dyspnea on exertion without overt congestion or elevated filling pressures at rest, yet demonstrate markedly elevated filling pressures during exercise 1, 2.

The Exercise-Dependent Nature of Early HFpEF

Patients in earlier stages of HFpEF may only display abnormal elevation in left ventricular filling pressure during exercise, while pressures remain completely normal at rest 3. This phenomenon explains why many patients with genuine HFpEF have:

• Normal resting LVEDP or pulmonary capillary wedge pressure (PCWP) <15 mm Hg 2
• Normal brain natriuretic peptide levels at rest 2
• No physical examination or radiographic signs of congestion 1

Yet during exercise hemodynamic testing, these same patients demonstrate:

• Exercise PCWP ≥25 mm Hg (diagnostic threshold for HFpEF) 2
• Exercise pulmonary artery systolic pressure ≥45 mm Hg (96% sensitivity, 95% specificity for HFpEF) 2
• Blunted increases in heart rate, systemic vasodilation, and cardiac output 2

Diagnostic Implications for Your Patient Population

In older women with hypertension, obesity, diabetes, chronic kidney disease, or atrial fibrillation—the exact demographic you describe—resting hemodynamics may be entirely normal despite symptomatic HFpEF 3. The 2022 AHA/ACC/HFSA guidelines explicitly acknowledge this: "The criteria for diagnosis of HFmrEF and HFpEF require evidence of increased LV filling pressures at rest, exercise, or other provocations" 3.

When to Suspect HFpEF Despite Normal Resting Pressures

The H2FPEF score can help identify patients who need exercise testing 3:

• Score 0-1: Low probability; pursue alternative diagnoses
• Score 2-5: Intermediate probability; exercise echocardiography or cardiac catheterization is required to confirm or exclude HFpEF 3
• Score ≥6: High probability (>95%) of HFpEF 3

The score incorporates: obesity, atrial fibrillation, age >60 years, ≥2 antihypertensive medications, E/e' >9, and PA systolic pressure >35 mm Hg 3.

The Biomarker Paradox in HFpEF

Normal or low-normal natriuretic peptide levels do NOT exclude HFpEF, particularly when resting filling pressures are normal 3, 4. This is because:

• BNP/NT-proBNP reflect current hemodynamic stress rather than structural abnormalities alone 5
• In euvolemic patients with normal resting PCWP, natriuretic peptides may be normal despite genuine diastolic dysfunction 2
• Obesity (common in HFpEF) suppresses BNP levels by 20-30%, potentially masking cardiac dysfunction 4, 5
• Approximately 29% of symptomatic HFpEF patients with elevated exercise PCWP have BNP ≤100 pg/mL 4

The 2009 ACC/AHA guidelines explicitly state: "A normal BNP level along with completely normal diastolic end-filling parameters makes HF much less likely; however, HF does remain a strictly clinical diagnosis" 3.

Recommended Diagnostic Approach

When HFpEF is suspected but resting hemodynamics are normal:

1. Calculate the H2FPEF score using clinical and resting echocardiographic data 3

2. If score 2-5 (intermediate probability), proceed to:

   • Exercise stress echocardiography with Doppler assessment of E/e' and estimated PA pressures 3, 6
   • OR invasive exercise hemodynamics measuring PCWP, PA pressures, stroke volume, and cardiac output during supine bicycle exercise 3, 2

3. Diagnostic thresholds during exercise:

   • Exercise PCWP ≥25 mm Hg confirms HFpEF 2
   • Exercise PA systolic pressure ≥45 mm Hg has 96% sensitivity and 95% specificity 2

Critical Clinical Pitfalls to Avoid

• Do not rely solely on resting hemodynamics to exclude HFpEF in patients with unexplained exertional dyspnea and typical risk factors 3, 2
• Do not dismiss the diagnosis based on normal BNP/NT-proBNP alone, especially in obese patients 4, 5
• Do not assume normal resting E/e' excludes HFpEF—diastolic parameters are readily altered by transient changes in loading conditions 3
• Recognize that earlier-stage HFpEF is fundamentally an exercise-induced hemodynamic disorder that may be completely masked at rest 3, 2

The key insight is that HFpEF exists on a spectrum: advanced disease presents with overt resting congestion and elevated filling pressures, while earlier disease manifests only during physiologic stress 1, 2. In your patient population (older women with metabolic comorbidities), a high index of suspicion and low threshold for exercise testing is warranted when exertional symptoms cannot be explained by alternative diagnoses 3, 1.