A Pilot Study Evaluating Heart and Lung Metabolism in Pulmonary Hypertension Associated With Left Heart Disease

Evaluation of Cardiopulmonary Metabolism and Pulmonary Vascular Remodeling in Pulmonary Hypertension Associated With Left Heart Disease

Right ventricular (RV) failure is the leading cause of death in pulmonary arterial hypertension. (PAH) Right ventricular ejection fraction is one of the most important predictors of prognosis in heart failure patients regardless of cause. It is estimated that 30-50% of patients with heart failure and preserved ejection fraction (HFpEF) have right ventricular dysfunction and up to 70% of these patients will have significant pulmonary hypertension (PH), both of which are related to much worse prognosis. Right ventricular failure is becoming an increasingly prevalent and significant cause of morbidity in patients with left heart disease. Despite the significance of RV function to survival, there are no therapies available that directly or selectively improve RV function.

The overall theme of this research project is to evaluate the mechanisms that contribute to the cause of right heart failure. This small study is designed to look at the role of heart and lung metabolism and pulmonary hypertension as they relate to the development of right heart failure in cardiovascular disease.(PH-LHD)

The hemodynamic definition of PH-LHD involves a mean pulmonary artery pressure (mPAP) >25mm Hg at rest and pulmonary capillary wedge pressure (PCWP) of ≥15.The coexistence of mitral insufficiency is also a characteristic of PH-LHD. HFpEF is a condition caused by impaired relaxation of a stiffened myocardium as a consequence of an increased load to the left ventricle due to elevated systemic pressures.

Pulmonary hemodynamics can be used to classify PH LHD as either passive or reactive, irrespective of LV function. It has been suggested that diastolic pressure gradient (DPG) may offer added prognostic value as a more accurate indicator of pulmonary vascular remodeling.

Inclusion Criteria:

• Patients must be able to provide their written informed consent to participate in the study after having received adequate previous information and prior to any study specific procedures.
• At least 18 years of age at the time of screening.
• Patients with PH secondary to left heart disease (known as group II PH) defined as a mean PAP>25 mmHg and a PCWP of ≥15 mmHg.

Exclusion Criteria:

• All other types of pulmonary hypertension including Dana Point Classification Group 1, 3, 5.
• Type II Diabetes mellitus requiring medical therapy
• Previous myocardial infarction within the 3 months prior to screening.
• Renal insufficiency (glomerular filtration rate < 30 ml/min.
• ALT or AST > 3times ULN and/or severe hepatic insufficiency.
• Contraindication to MRI imaging.