The Prospective Risk Factor Evaluation & Discovery In CTEPH Study

Chronic thromboembolic pulmonary hypertension (CTEPH) is due to non-resolution of pulmonary
embolism (PE), and is the most serious long-term sequela of PE. Without treatment, CTEPH
leads to progressive right heart failure and death. Fortunately, most cases of CTEPH are
potentially curable by a surgical procedure in which the chronic thromboembolic material is
removed from the pulmonary arterial tree, and for those who are not surgical candidates a
novel medical therapy is now available. Multiple studies have shown, however, that the
majority of CTEPH cases go undiagnosed, and thus many symptomatic patients are never offered
these potentially beneficial treatments. Because persistent dyspnea affects up to 50% of
patients who survive an acute PE, selecting which patients should undergo further invasive
testing for CTEPH is a difficult clinical problem. In this study, the investigators propose
to prospectively follow a cohort of high-risk patients after acute PE until CTEPH is either
diagnosed or excluded, and perform serial collection and banking of biospecimens that will
allow for prospective and longitudinal screening of biomarkers that might predict future risk
of CTEPH. Biomarker screening will initially be focused on a panel of 20 pre-specified plasma
proteins with roles in coagulation/fibrinolysis or inflammation, as well as assays of
fibrinolysis, as these are processes that existing literature suggests are linked to the
pathophysiology of CTEPH. The biorepository created for this study could also be used in the
future to perform unbiased screening with proteomic techniques or RNAseq in the hopes of
identifying novel biomarkers and novel biological processes that are relevant to the
development of CTEPH. As there is no current consensus as to whether structured follow-up
after PE to detect signs and symptoms of CTEPH is beneficial, this study also includes an
analysis of whether a novel structured follow-up program improves identification of incident
CTEPH cases. This study has the potential to dramatically improve post-PE care by
facilitating stratification of patients by future risk of CTEPH at the time of acute PE, thus
allowing for expert follow-up to be tailored to those patients at highest risk for CTEPH. The
investigators hope that these efforts will improve the rate at which CTEPH cases are
identified, so that more patients can benefit from existing treatments.

Inclusion Criteria:

i. Age ≥ 18 years.

ii. Presence of pulmonary embolism (PE) objectively diagnosed by ventilation/perfusion
(V/Q) scan or computed tomography pulmonary angiography (CTPA).

iii. Plus one of:

- Prior history of PE before the index event (predicted 2-year incidence of chronic
thromboembolic pulmonary hypertension (CTEPH) of 35%).

- Transthoracic echocardiogram (TTE) performed within 72 hours of PE diagnosis
demonstrating a maximum velocity of the tricuspid regurgitant (TR) jet ≥ 3.0
meters/second (predicted 2-year incidence of CTEPH of approximately 25%).

- CTPA demonstrating involvement of one of the main pulmonary arteries with PE
(predicted 2-year incidence of CTEPH of approximately 15%).

- CTEPH prediction score ≥ 6 (this score is based on several clinical factors, including
unprovoked nature of the PE, presence of right ventricular dysfunction by CTPA or TTE,
presence of hypothyroidism or diabetes, and thrombolytic therapy for PE).

Exclusion Criteria:

i. The patient previously met diagnostic criteria for pulmonary hypertension of any cause.

ii. Presence of significant left ventricular systolic dysfunction (defined by left
ventricular ejection fraction ≤ 45% by TTE), or left sided valvular disease (including
mitral or aortic regurgitation or stenosis).

iii. Age > 85 years.

iv. The presence of metastatic malignancy (due to the expected limitation of lifespan to
less than the study follow-up period of 2 years).

v. The presence of a significant psychiatric disorder or significant cognitive impairment,
which would make follow-up and/or symptom reporting difficult.

vi. Inability or unwillingness to attend follow-up clinic appointments at Intermountain
Medical Center (including geographical, financial, and insurance limitations).