Unclassified pulmonary hypertension most often reflects subclinical left heart and metabolic dysfunction consistent with unrecognized early-stage heart failure with preserved ejection fraction (HFpEF).
In a combined cohort of 2,248 participants, unclassified PH had a prevalence of 7.8%. Among those with unclassified PH, 59% (72/122) showed exertional pulmonary artery wedge pressure elevation consistent with undiagnosed HFpEF during exercise testing. The condition was associated with greater adiposity, higher HFpEF probability scores, left heart remodeling, and lower glycine metabolites indicative of metabolic dysfunction.
Evidence Score
Study Evidence
Study 1. Phenotypic Characterization of Unclassified Pulmonary Hypertension.
observationalReddy YNV, Frantz RP, Egbe AC, Miranda WR, Asokan AK, Hassoun PM, Hemnes AR, Horn E, Leopold JA, Rischard F, Rosenzweig EB, Hill NS, Erzurum SC, Finet JE, Mukherjee M, Tang WHW, Nair KS, Borlaug BA · Circulation. Heart failure (2026)
Result:
Mechanism Graph
Limitations
- ⚠Observational study design limits causal inference
- ⚠Prevalence estimates may not generalize to all populations due to cohort-specific referral patterns
Frequently Asked Questions
What is unclassified pulmonary hypertension?▼
Unclassified PH is a condition where symptomatic patients have pulmonary hypertension despite normal pulmonary vascular resistance and pulmonary artery wedge pressure, often thought to reflect increased blood flow.
How common is unclassified PH?▼
The overall prevalence was 7.8% across the main cohorts (175 out of 2,248 participants), with higher prevalence in high output heart failure (14.5%) and lower in adult congenital heart disease (6.6%).
What does unclassified PH indicate about heart health?▼
The study suggests unclassified PH most often reflects subclinical left heart and metabolic dysfunction consistent with unrecognized early-stage heart failure with preserved ejection fraction (HFpEF).
Can exercise testing help diagnose the underlying cause?▼
Yes, dynamic provocation during right heart catheterization with exercise unmasked unrecognized HFpEF in 59% of patients with unclassified PH.
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References
- 1.Reddy YNV, Frantz RP, Egbe AC, Miranda WR, Asokan AK, Hassoun PM, Hemnes AR, Horn E, Leopold JA, Rischard F, Rosenzweig EB, Hill NS, Erzurum SC, Finet JE, Mukherjee M, Tang WHW, Nair KS, Borlaug BA. "Phenotypic Characterization of Unclassified Pulmonary Hypertension.." Circulation. Heart failure, 2026. PMID: 42318624 DOI: 10.1161/CIRCHEARTFAILURE.125.014480