Cardiac Assessment by PV Loop in IPAH and Scleroderma PAH

Study Overview
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Brief Summary
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This observational study is being done to understand why people with scleroderma can develop pulmonary arterial hypertension (high blood pressure in the lungs, abbreviated PAH) and a weak heart muscle (heart failure). The study will also help the investigators understand why people with PAH from an unknown cause (called idiopathic PAH, or IPAH) can also develop a weakened heart muscle. The response of the right side of the heart or right ventricle (RV) to standard PAH therapy in scleroderma-associated PAH and in IPAH will be assessed. Blood and tissue samples will be collected from research participants during participants' normal standard of care procedures. People with scleroderma-associated PAH or idiopathic cause (IPAH) who need a right heart catheterization may join this study.

Detailed Description
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Patients with scleroderma associated pulmonary hypertension (with or without interstitial lung disease) have a worse prognosis compared to patients with idiopathic pulmonary arterial hypertension (IPAH). The investigators have discovered through a previous protocol that patients with scleroderma associated pulmonary hypertension (SSc-PAH) have intrinsic right ventricular (RV) contractile dysfunction compared with patients with idiopathic pulmonary hypertension (IPAH) despite similar afterload imposed by the pulmonary vasculature. Patients with scleroderma or presumed/known IPAH who are clinically referred for right heart catheterization (RHC) will undergo, in addition to a clinically indicated RHC, state-of-the-art Pressure-Volume (P/V) Loop Assessment and RV biopsy for research purposes. The investigators will also do a standard pathologic assessment of the RV tissue (H&E, special staining, electron microscopy), microvascular density measurements using immunohistochemistry techniques and isolated skinned myocyte experiments. Additional experiments will include proteomics, genomics/genetics, and RV protein and microRNA expression. The investigators will compare these findings in both groups (IPAH and SSc-PAH), before and after standard treatment for 6 months, in order to fully understand the differences in how the RV adapts to pressure overload and reasons for impaired RV function in SSc-PAH as well as identifying potential therapeutic targets.

Official Title
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Understanding Right Ventricular Heart Failure in Scleroderma and Idiopathic Pulmonary Arterial Hypertension

Conditions
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Scleroderma, Pulmonary Artery Hypertension

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years or older with clinically diagnosed scleroderma or presumed/known idiopathic pulmonary hypertension. Exclusion Criteria: Patients found to have secondary pulmonary hypertension (PH due to left heart failure) on clinical RHC. Hemodynamically unstable patients (systolic blood pressure < 90mmHg, vasopressor requirement). Patients whom are unable to give consent for themselves. Patients with RV clot or septal aneurysm will be excluded. In order to undergo the clinical right heart catheterization procedures, pregnancy testing (urine or serum) is standard of care. Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SSc-PAH Group<br>Scleroderma patients referred for a clinically indicated right heart catheterization (RHC). | |
| IPAH Group<br>Presumed/known IPAH patients referred for a clinically indicated right heart catheterization (RHC). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right Ventricular Function as assessed by RHC | Assessed on the clinical RHC as normal, moderately reduced, or severely reduced. | Baseline | 
| Change in pulmonary vascular resistance | Assessed as improved or decreased after 6 months by comparing the change in pulmonary vascular resistance in Wood units on the clinical RHC. | Baseline and 6months | 
| Change in arterial elastance | Assessed as improved or decreased after 6 months by comparing the change in arterial elastance in pressure volume (PV) loops. | Baseline and 6 months | 
| Change in myofilament contractility | Assessed as Normal or Abnormal after studying the collected samples in lab. Abnormal can be either reduced or increased; i.e. hyper- or hypo-contractile. | up to 4 years | 
| Change in calcium sensitivity | Assessed as either increased- or decreased- sensitivity after 6 months, by studying the collected samples in lab. | up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of genes expressed | Gene expression as assessed by observing presence of microRNA in the lab. | up to 4 years | 
| Number of proteins expressed | Protein expression as assessed by observing post-translational modification of candidate proteins in the lab. | up to 4 years |