If It Quacks Like PH, But It’s Not PH, Think EIPH

FIT Author: Anezi Uzendu, MD*
Additional Authors: Mark McIntyre and Saurabh Rajpal, MD*

A 47-year old female presented for evaluation of dyspnea on exertion and hypoxemia observed during a dental procedure. Past medical history included closure of patent ductus arteriosus at 11 months and closure of a ventricular septal defect at 15 months. On exam she had a loud P2 and a soft systolic murmur at tricuspid area. Resting O2 saturations were 95%, on exercise O2 saturation dropped to 79%. CT chest showed ground glass opacities, enlarged pulmonary arteries (PAs) and no acute pulmonary embolism. She had a negative nuclear stress test, pulmonary function testing with mild restriction, an echo with a right ventricular systolic pressure of 40mmHg and a small secundum atrial septal defect (ASD). Cardiac MRI showed mildly decreased right ventricular systolic function (RVEF 35%) and a QpQs of 1.1

To summarize, our patient had severe dyspnea with exertion, hypoxemia with activity, and signs of pulmonary hypertension (loud P2 and enlarged PAs) and an ASD, shunting through which would explain the marked hypoxemia on exercise. Surprisingly right heart catheterization was not consistent with significant pulmonary hypertension (see figure 3).

Thus, an exercise right heart catheterization was pursued which clinched the diagnosis. Results were as follows (in mm hg): RA 10, RV 42/10, PA 39/20/28 PCW 13 at rest; with exercise PA 83/19/55, cardiac output (CO) of 8L/min. These results show a ~30 mm hg increase in PA pressures with exercise with only minimal change in PA diastolic pressures, (See figure 4) suggesting exercise induced pulmonary hypertension (EIPH).

EIPH is an increase in mean pulmonary artery pressures (mPAP) greater than 30 mmHg at a CO less than 10L/min and total pulmonary resistance (TPR) greater than 3 woods units during exercise(1). The defined relationship between mPAP and CO is generally linear with an average slope of ~1 mmHg*L/min-1. In contrast, in EIPH there is an abnormal increase in pulmonary vascular resistance or left heart filling pressures leading to a slope ~ 3 mmHg*L/min-1.

EIPH is not benign.(2-4) There is an association with increased mortality and progression to pulmonary hypertension. Like resting pulmonary hypertension, evaluation should be based on the underlying etiology. In patients with EIPH attributed to increased pulmonary resistance, treatment with pulmonary vasodilator therapy led to improved exercise hemodynamics and capacity (5). Continued efforts into identifying patients and defining this disease entity are needed to assess the depth of its reach and change its current paradigm.

1. Naeije R, Saggar R, Badesch D, Rajagopalan S, Gargani L, Rischard F, et al. Exercise-Induced Pulmonary Hypertension: Translating Pathophysiological Concepts Into Clinical Practice. Chest. 2018. Epub 2018/02/01. doi: 10.1016/j.chest.2018.01.022. PubMed PMID: 29382472.
2. Magne J, Lancellotti P, Piérard LA. Exercise Pulmonary Hypertension in Asymptomatic Degenerative Mitral Regurgitation. Circulation. 2010;122(1):33.
3. Lancellotti P, Magne J, Donal E, Connor K, Dulgheru R, Rosca M, et al. <span hwp:id=”article-title-1″ class=”article-title”>Determinants and Prognostic Significance of Exercise Pulmonary Hypertension in Asymptomatic Severe Aortic Stenosis</span><span hwp:id=”article-title-35″ class=”sub-article-title”>Clinical Perspective</span>. Circulation. 2012;126(7):851.
4. Stamm A, Saxer S, Lichtblau M, Hasler ED, Jordan S, Huber LC, et al. Exercise pulmonary haemodynamics predict outcome in patients with systemic sclerosis. European Respiratory Journal. 2016;48(6):1658.
5. Saggar R, Khanna D, Shapiro S, Furst DE, Maranian P, Clements P, et al. Brief Report: Effect of ambrisentan treatment on exercise‐induced pulmonary hypertension in systemic sclerosis: A prospective single‐center, open‐label pilot study. Arthritis & Rheumatism. 2012;64(12):4072-7. doi: 10.1002/art.34614

*The Ohio State University, Columbus, OH