Multimodality Deep Phenotyping Methods to Assess Mechanisms of Poor Right Ventricular-Pulmonary Artery Coupling

Area of Science:

• Cardiology
• Pulmonary Medicine
• Biomedical Engineering

Background:

• Pulmonary hypertension (PH) diagnosis and management benefit from precise phenotyping.
• Multimodal exercise interventions offer a dynamic approach to assess cardiovascular function.
• Understanding right ventricular:pulmonary arterial (RV:PA) coupling is crucial for PH prognosis.

Purpose of the Study:

• To develop and pilot methods for simultaneous assessment of pulmonary impedance, biventricular myocardial strain, and RV:PA coupling during exercise in suspected PH.
• To demonstrate distinct physiological responses to exercise across different PH etiologies.
• To explore the utility of deep phenotyping in distinguishing mechanisms of RV:PA uncoupling.

Main Methods:

• Simultaneous measurement of pulmonary impedance (input Z0, characteristic ZC), differential biventricular myocardial strain, and RV:PA coupling during graded exercise.
• Pilot study in four subjects with pulmonary arterial hypertension (PAH), chronic thromboembolic disease (CTEPH), PH with preserved ejection fraction (PH-HFpEF), and noncardiac dyspnea (NCD).

Main Results:

• Distinct exercise response patterns observed across PH subtypes.
• RV:PA coupling during exercise ranked highest to lowest: PAH > CTEPH > PH-HFpEF > NCD.
• Input impedance (Z0) was highest in precapillary PH (PAH, CTEPH), lower in PH-HFpEF and NCD.
• Characteristic impedance (ZC) generally decreased with exercise, with an exception in PH-HFpEF.
• Reduced interventricular septal strain noted in the PH-HFpEF subject, correlating with impaired RV:PA coupling due to left ventricular support issues.

Conclusions:

• Deep phenotyping with multimodal exercise interventions provides novel insights into RV:PA uncoupling mechanisms in PH.
• This approach can differentiate between afterload-sensitive and left ventricle-dependent RV:PA uncoupling.
• Findings suggest potential for improved diagnostic accuracy and targeted therapeutic strategies in PH.