Clinical trial NCT04610788: Cardiac Assessment by PV Loop in IPAH and Scleroderma PAH
Official title: Understanding Right Ventricular Heart Failure in Scleroderma and Idiopathic Pulmonary Arterial Hypertension
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Scleroderma
Pulmonary Artery Hypertension
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2020-11-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients 18 years or older with clinically diagnosed scleroderma or presumed/known idiopathic pulmonary hypertension.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Right Ventricular Function as assessed by RHC
timeFrame: Baseline
measure: Change in pulmonary vascular resistance
timeFrame: Baseline and 6months
measure: Change in arterial elastance
timeFrame: Baseline and 6 months
measure: Change in myofilament contractility
timeFrame: up to 4 years
measure: Change in calcium sensitivity
timeFrame: up to 4 years
Secondary outcomes:
measure: Number of genes expressed
timeFrame: up to 4 years
measure: Number of proteins expressed
timeFrame: up to 4 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Paul Hassoun, MD
role: PRINCIPAL_INVESTIGATOR
References: