In pulmonary arterial hypertension (PAH), progressive pulmonary vascular remodeling leads to supraphysiologic right ventricular (RV) afterload. Pharmacologic trials have shown that aggressive upfront treatment reversing pulmonary vascular remodeling successfully increases RV function and improves survival. To date, however, there are no proven treatments that target RV contractile function.

Echocardiographic studies of RV dysfunction in the setting of pressure overload have demonstrated intra and interventricular dyssynchrony even in the absence of overt right bundle branch block (RBBB).

Electrophysiologic studies of patients with chronic thromboembolic disease (CTEPH) at the time of pulmonary endarterectomy have shown prolongation of action potential and slowed conduction in the right ventricle which has correlated with echocardiographic measures of dyssynchrony.

Cardiac MRI measures of RV strain in patients with PAH demonstrated simultaneous initiation of RV and left ventricular (LV) contraction, but delayed peak RV strain suggesting that interventricular dyssynchrony is a mechanical rather than electrical phenomenon.

Prior studies of RV dysfunction in an animal model, computer model, congenital heart disease, and CTEPH have suggested acute hemodynamic benefits of RV pacing. However, RV pacing has not been studied in patients with PAH. Furthermore, it remains unclear if pacing particular regions of the RV can achieve a hemodynamic benefit and what cost this hemodynamic improvement may incur with regards to myocardial energetics and wall stress.

Therefore, the investigators propose to examine RV electrical activation in PAH, map the area of latest activation, and then evaluate the hemodynamic and energetic effects of RV pacing in these patients.

Research procedures in chronological order:

1. Baseline clinical variables will be prospectively determined and then obtained retrospectively from the clinical assessment of individual pulmonary hypertension team physicians via chart review. The most recent transthoracic echocardiogram will also be evaluated and routine clinical variables including tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (FAC), RV outflow tract (OT) and LVOT velocity time integral (VTI), and ejection fraction (EF) will be extracted.
2. All patients will have cardiac MRI performed prior to the procedure to allow precise measurement of right ventricular volumes as well as LV volumes, RVEF, and LVEF. Gadolinium enhancement using gadolinium contrast will be measured.
3. Standard of care right heart catheterization (RHC) will be performed on the day of the research procedure.
4. Radial arterial pressure will be used for periprocedural monitoring as well as for sampling of arterial oxygen content and arterial oxygen lactate.
5. Myocardial energetics will be assessed via sampling of coronary sinus venous blood with measurement of oxygen saturation and lactate.
6. Following the standard of care RHC, endocardial mapping will be performed. After pressure-volume measurements are obtained (step 7), pacing will be performed from the right atrium (RA), His bundle, and RV at the site of the latest activation with repeat measurements of pressure-volume relationships.
7. Once endocardial mapping is complete, a 7-French Millar conductance catheter will be placed into the RV and used to obtain pressure-volume data for the RV using the INCA PV signal processor. The Valsalva maneuver will be used to generate a series of PV-loops reflecting preload reduction subsequently allowing for the calculation of a load independent measure of contractility, the end systolic pressure volume relationship (Ees). RV afterload will be measured as effective arterial elastance (Ea) and V-A coupling will be assessed by the ratio of Ees/Ea. Myocardial energetics will be assessed via PV area (PVA) and calculation of the transmyocardial arteriovenous oxygen extraction.

Inclusion Criteria:

• Patients referred for a clinically indicated right heart catheterization to either diagnose pulmonary arterial hypertension prior to initiating therapies or monitor response to ongoing therapies in patients with diagnosed pulmonary arterial hypertension.
• Patients with pulmonary arterial hypertension with or without significant right ventricular dysfunction as assessed by baseline echocardiography and standard of care right heart catheterization
• Functional class 2 or 3 symptoms
• Are able to undergo cardiac MRI, endocardial mapping, and pressure volume measurements
• English speaking
• All patients will be required to have evidence of right ventricular hypertrophy or conduction delay (QRS > 130ms) on surface ECG

Exclusion Criteria:

• Preexisting left bundle branch block, current atrial fibrillation, or pacemaker/ defibrillators
• Functional class 4 symptoms
• Patients treated with parenteral or subcutaneous therapies for pulmonary hypertension
• Contraindication to right heart catheterization including significant thrombocytopenia (platelets < 50,000), coagulopathy (INR > 1.8), or pregnancy as determined by routine screening laboratory work
• Mean pulmonary artery pressure less than 25 mmHg as determined by the right heart catheterization on the day of the study procedure
• Pulmonary capillary wedge pressure greater than or equal to 15 mmHg as determined by the right heart catheterization on the day of the study procedure
• Severe tricuspid regurgitation as determined by baseline transthoracic echocardiogram.
• Left ventricular dysfunction (EF < 50%) as determined by baseline transthoracic echocardiogram.
• Inability to complete cardiac MRI or transthoracic echocardiography
• Patients with confounding systemic disease specifically portopulmonary hypertension and scleroderma associated pulmonary hypertension
• Patients otherwise deemed not appropriate for the study as determined by the study investigators