Resolving Diagnostic Discordance in Group 2 Pulmonary Hypertension Through Staged Physiologic Testing: Insights From...

Area of Science:

• Cardiology
• Pulmonary Hypertension
• Left Heart Disease

Background:

• Group 2 pulmonary hypertension (PH) is linked to left heart disease, with pre- vs. post-capillary classification based on pulmonary capillary wedge pressure (PCWP).
• Current guidelines suggest contextual interpretation and provocative testing for intermediate PCWP, but the relationship between PCWP and phenotype is unclear.
• Systematic evaluation of phenotype-hemodynamic discordance and a physiology-guided framework are needed.

Purpose of the Study:

• To quantify phenotype-hemodynamic discordance across the PCWP spectrum in Group 2 PH.
• To evaluate a staged, physiology-guided framework using inhaled nitric oxide (iNO), ventricular geometry, and provocative testing.
• To improve the concordance between hemodynamic classification and clinical phenotype in PH.

Main Methods:

• Studied 1,032 participants from the NHLBI PVDOMICS cohort with multidisciplinary adjudicated phenotypes.
• Classified pre- vs. post-capillary physiology at rest, during iNO, and during provocative testing (fluid challenge or iCPET).
• Evaluated echocardiographic right ventricular-to-left ventricular (RV/LV) ratio and used restricted cubic spline/staged concordance analyses.

Main Results:

• Resting PCWP showed good discrimination (AUC 0.86) but significant discordance persisted at intermediate values.
• Dynamic testing and iNO improved concordance, increasing Group 2 PH identification by 63.4% and sensitivity.
• RV/LV ratio and PCWP/cardiac output slope provided complementary information for resolving discordant classifications.

Conclusions:

• Group 2 PH is dynamic and load-dependent, inadequately characterized by resting PCWP alone.
• Intermediate PCWP values represent continuous probabilities of discordance, not discrete diagnostic states.
• A staged, physiology-guided approach integrating iNO, ventricular geometry, and provocative testing enhances classification accuracy.