In older women with hypertension, obesity, diabetes, chronic kidney disease, or atrial fibrillation, can heart‑failure with preserved ejection fraction and a normal left‑ventricular end‑diastolic pressure cause an elevated pulmonary capillary wedge pressure during right‑heart catheterization for suspected Group 2 pulmonary hypertension?

Can HFpEF with Normal LVEDP Explain Elevated PCWP in Group 2 Pulmonary Hypertension?

Yes, HFpEF can absolutely cause elevated PCWP during right heart catheterization even when LVEDP appears normal at rest, particularly in older women with hypertension, obesity, diabetes, chronic kidney disease, or atrial fibrillation—this represents one of the most challenging diagnostic scenarios in pulmonary hypertension evaluation. 1

The Core Diagnostic Challenge

The critical issue is that PCWP and LVEDP can be "pseudo-normal" at rest, especially when patients have been treated with diuretics, masking underlying left ventricular diastolic dysfunction. 1 This phenomenon makes HFpEF one of the most challenging differential diagnoses in patients presenting with suspected pulmonary hypertension. 1

Why This Occurs

• Diastolic dysfunction in HFpEF is characterized by elevated left ventricular stiffness, prolonged iso-volumetric LV relaxation, slow LV filling, and elevated LV end-diastolic pressure—but these abnormalities may not be apparent at rest after diuretic therapy. 2

• In the HFpEF population, PCWP may be mildly elevated or at the higher end of the normal range at rest, yet still reflect significant left heart disease. 1

• Approximately 22% of patients with mean pulmonary artery pressure 19-24 mmHg and 78% with mean PAP >25 mmHg have elevated PCWP (>15 mmHg), demonstrating how common post-capillary pulmonary hypertension is in this population. 3

Hemodynamic Definitions and Thresholds

Normal PCWP values are ≤12 mmHg; values >15 mmHg are considered elevated and indicate increased left ventricular filling pressures. 4, 5, 3 A PCWP >15 mmHg excludes the diagnosis of pre-capillary pulmonary arterial hypertension and confirms Group 2 (post-capillary) pulmonary hypertension due to left heart disease. 1

Critical Measurement Considerations

• Measurements must be taken at end-expiration of a spontaneous respiratory cycle to minimize respiratory variations. 4, 5

• Multiple measurements from different pulmonary segments improve accuracy as values may vary between lung segments. 4, 5

• The external pressure transducer must be zeroed at the mid-thoracic line (halfway between anterior sternum and bed surface) in a supine patient. 5

When LVEDP and PCWP Diverge

In rare cases, left heart catheterization may be required for direct assessment of left ventricular end-diastolic pressure when PCWP is uncertain or potentially inaccurate. 1 This is particularly important because:

• PCWP may not accurately reflect LVEDP in certain conditions, including left ventricular hypertrophy, diabetes, obesity, and ischemia—all common in the HFpEF population. 3

• Direct LVEDP measurement is particularly recommended when left heart disease is the likely etiology, such as in patients with orthopnea or associated risk factors. 5

• The threshold to perform left heart catheterization in addition to right heart catheterization should be low in patients with clinical risk factors for heart failure with preserved ejection fraction. 1

Exercise Hemodynamic Challenge: Unmasking Hidden HFpEF

In the setting where resting hemodynamics appear normal or borderline, exercise hemodynamic challenge has been proposed to identify left ventricular dysfunction, though these diagnostic tools require further standardization. 1 This approach is particularly valuable because:

• Approximately 35% of patients with HFpEF present with "unexplained" dyspnea on exertion without clear physical, radiographic, or echocardiographic signs of HF at rest. 6

• These patients have elevated atrial pressures with exercise as measured with invasive hemodynamic stress testing or estimated with Doppler echocardiography stress testing. 6

Clinical Risk Factors That Predict Elevated PCWP

In your specific patient population (older women with hypertension, obesity, diabetes, chronic kidney disease, or atrial fibrillation), multiple validated risk factors strongly predict elevated PCWP and HFpEF:

• Body mass index ≥30 (morbid obesity) has an odds ratio of 3.4 for pulmonary hypertension in patients with elevated LVEDP and preserved ejection fraction. 7

• Atrial fibrillation has an odds ratio of 3.1 for pulmonary hypertension in this population. 7

• LVEDP ≥25 mmHg has an odds ratio of 4.3 for pulmonary hypertension, though remember that resting LVEDP may be pseudo-normal. 7

• Age ≥80 years, chronic kidney disease (implied by chronic obstructive pulmonary disease association), and dyspnea on exertion are all significantly associated with PH development. 7

Noninvasive Prediction Tools

The H2FPEF score (incorporating age, hypertension, obesity, atrial fibrillation status, and Doppler echocardiographic variables) can assist with diagnosis—a score >5 indicates more than 95% probability of HFpEF. 6 However, high probability of heart failure with preserved ejection fraction (H2FPEF score ≥6) was less specific for postcapillary PH than the OPTICS risk score in predicting elevated PCWP. 8

The OPTICS risk score (incorporating BMI ≥30, diabetes mellitus, atrial fibrillation, dyslipidemia, history of valvular surgery, ECG parameters, and left atrial dilation) has 100% specificity for postcapillary PH when >104, though with only 22% sensitivity. 8

Distinguishing Combined Pre- and Post-Capillary PH

An elevated transpulmonary gradient (mean PA pressure - PCWP) >12 mmHg is suggestive of intrinsic changes in the pulmonary circulation overriding the passive increase in PCWP. 1 This indicates combined pre- and post-capillary pulmonary hypertension rather than isolated post-capillary PH. 3

• Isolated post-capillary PH is characterized by mean PAP >20 mmHg, PCWP >15 mmHg, and PVR <3 Wood units. 3

• Combined pre- and post-capillary PH is characterized by mean PAP >20 mmHg, PCWP >15 mmHg, and PVR ≥3 Wood units. 3

Critical Pitfalls to Avoid

• Never rely on a single resting PCWP measurement in patients with strong clinical risk factors for HFpEF—consider exercise hemodynamics or direct LVEDP measurement if uncertainty exists. 1

• Do not assume normal LVEDP excludes HFpEF if the patient has been aggressively diuresed—pseudo-normal pressures are common. 1

• Avoid measuring PCWP during active expiratory muscle recruitment, hyperventilation, or Valsalva maneuvers, which create exaggerated pressure swings. 5

• Ensure proper wedge position by confirming characteristic a and v waves and obtaining blood gas from wedged position showing arterial-level oxygen saturation. 5

• Account for conditions that affect PCWP accuracy: severe tricuspid regurgitation, positive end-expiratory pressure ventilation, and atrial fibrillation all invalidate standard measurements. 5, 3

Prognostic Implications

Of 455 patients with LVEDP >15 mmHg and preserved ejection fraction, 239 (52.5%) had pulmonary hypertension, demonstrating how common this scenario is. 7 Mortality in PH-HFpEF is 23.6% at 1 year and 48.2% at 5 years, with cardiac hospitalizations occurring in 28.1% at 1 year and 47.4% at 5 years. 9