Interferon-β-Induced Pulmonary Arterial Hypertension: Approach to Diagnosis and Clinical Monitoring

Abstract

A 48-year-old woman who had been receiving long-term interferon-β for 8 years for multiple sclerosis developed drug-induced World Health Organization group I pulmonary arterial hypertension. Triple therapy for pulmonary arterial hypertension and suspension of interferon-β led to improvement from a high-risk to low-risk state and improvement in exercise hemodynamics, including vascular distensibility, and right ventricle-pulmonary artery coupling. (Level of Difficulty: Advanced.).

Keywords: 6MWD, 6-min walk distance; BNP, B-type natriuretic peptide; BP, blood pressure; CMR, cardiac magnetic resonance; CPET, cardiopulmonary exercise test; Dlco, diffusion capacity of carbon monoxide; ET, endothelin; IFN, interferon; MS, multiple sclerosis; NYHA, New York Heart Association; PA, pulmonary arterial; PAH, pulmonary arterial hypertension; RHC, right-sided heart catheterization; RV, right ventricular; exercise; pulmonary hypertension; right ventricle.

Graphical abstract

Figure 1

Timeline of Clinical Course With Improvement From High-Risk to Low-Risk State (A) Overview. (B) Specific values. ∗Echocardiography-based coupling parameter (ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure [TAPSE/PASP]) (12). ^λCardiac magnetic resonance–based right ventricular ejection fraction (RVEF). ^†Ratio of end-systolic elastance (Ees) to arterial elastance (Ea) (Ees/Ea) as a marker of right ventricular–pulmonary arterial coupling, on the basis of the single-beat method (details in Figure 3). BNP = B-type natriuretic peptide; CPET = cardiopulmonary exercise test; IFN = interferon; IV = intravenous; PAH = pulmonary arterial hypertension; PVR = pulmonary vascular resistance; 6MWD = 6-min walk distance.

Figure 2

Improvement of RV Morphology and Function: Pre- and Post-Treatment Pre- and post-treatment normalization of (A and B) right ventricular (RV) outflow tract Doppler waveform notching pattern (reflects increased right ventricular afterload), (C and D) dilated right ventricular apex, (E and F) interventricular septal flattening, and (G and H) severe right atrial dilation and pericardial effusion.

Figure 3

Right Ventricular Pressure Volume Loops Pre- and Post-Treatment on the Basis of the Single-Beat Method (Volume Estimated With CMR) Solid lines indicate calculated quantities; dashed lines are theoretical. Right ventricular–pulmonary arterial coupling was defined as the ratio of end-systolic elastance (Ees) to arterial elastance (Ea), the Ees/Ea ratio. Before single-beat analysis, the right ventricular traces were shifted down to obtain an end-diastolic pressure of approximately zero (11). ESP = end-systolic pressure; Pmax = maximum pressure reached by an isovolumic heartbeat.