Lower DLco-percent in patients with lung disease may be a sign of exercise pulmonary hypertension

Liz Meszaros, MDLinx | June 16, 2017

Check for underlying pulmonary vascular disease in patients with a very low diffusion of the lungs for carbon monoxide (DLco%), as this may signify the presence of exercise pulmonary hypertension (ePH), according to results presented in Washington, DC, in late May at the American Thoracic Society 2017 International Conference.

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Looking for exercise pulmonary hypertension

Very low diffusion of the lungs for carbon monoxide (DLco%), as this may signify the presence of exercise pulmonary hypertension (ePH).

“Exercise pulmonary arterial hypertension has been a phenomenon that’s been noted for quite some time, but in about 2008, at the World Health Organization meeting, they got rid of the definition for ePH, primarily because there was a lack of standardization in how the studies were done and how they defined it,” explained lead researcher Michael G. Risbano, MD, MA, FCCP, assistant professor of medicine; director, Invasive Cardiopulmonary Exercise Testing Program; and head, Clinical Operations for Pulmonary Hypertension, University of Pittsburgh Medical Center, Montefiore Hospital, Pittsburgh, PA.

“Since then, there have been a lot of groups looking at how to define ePH. What people seem to be settling on is the relationship of the pulmonary artery pressures to the flow, cardiac output. That relationship may define what is an abnormal pulmonary vascular response to exercise,” he said.

Exercise pulmonary arterial hypertension is currently characterized by an mean pulmonary artery pressure (mPAP)max ≥ 30 mmHg, with a cardiac output (CO) of < 10 L/min and total pulmonary vascular (TPR) resistancemax ≥ 3.0 WU or the slope of the mPAP/CO ratio > 3.0 mmHg/L/min.1

Dr. Risbano and colleagues included 80 patients who had undergone exercise right heart catheterization (exRHC) between March 2012 and May 2017 at the University of Pittsburgh, Pittsburgh, PA. They analyzed 43 consecutive supine exRHC studies in which patients had normal resting mPAP and pulmonary artery wedge pressure (PAWP), with at least four hemodynamic values from resting to peak exercise.

Patients with a resting pulmonary arterial hypertension mPAP > 25 mm Hg, elevated resting PAWP > 15 mmHg, structural cardiac abnormalities, severe mitral/aortic valvular disease, or LVEF by echocardiogram < 45% were excluded. Using Kruskal-Wallis or Fisher’s exact test, they did pairwise comparisons of the two subject populations for baseline variables.

In the low DLco% group, most patients had underlying lung disease. Among patients with normal resting hemodynamics and an ePH diagnosis, those with a DLco% < 50% had a higher baseline resting transpulmonary gradient (TPG) compared with those with DLco% > 50% (21 mmHg vs 17.2, respectively; P=0.08) and pulmonary vascular resistance. At peak exercise, patients with a DLco% < 50% had a significantly higher mPAP compared with those with DLco% > 50% (35.0 vs 29.8 mmHg, respectively; P=0.01), total pulmonary resistance (TPR; 3.5 vs 2.3 WU; P=0.004), and pulmonary vascular resistance (PVR; 2.5 VS 1.7 WU; P=0.021) and lower cardiac output and index (see table).

“In a referral population, if there tends to be a lot of underlying pulmonary disease, and if you have a low DLco%, there may be more ePH. If you are going to refer them to figure out why they may be breathless, if they have pulmonary function tests that haven’t changed much, and if you’re trying to figure out if there’s anything we can substantially reverse or fix, you can look and see if there’s underlying pulmonary vascular disease in patients with a very low DLco%. It’s still very controversial whether we should be treating these people or not,” concluded Dr. Risbano.

Reference: 1. Herve P, Lau EM, Sitbon O, et al. Criteria for diagnosis of exercise pulmonary hypertension. Eur Resp J. 2015;46:728-737.

Peak Exercise

DLco >50%

Median (IQR)

DLco <50%

Median (IQR)

P-value

n

32

11

Exercise Parameters

     Duration of exercise (min)

13 (11-19)

9 (9-12)

0.019

     METS

4.9 (4.0-6.1)

3.7 (3.2-6.1)

0.025

     Maximum Workload (Watts)

75 (60-100)

50 (40-70)

0.028

     HR (mm Hg)

72 (62-82)

76 (59-81)

0.80

     SBP (mm Hg)

158 (145-187)

190 (157-200)

0.14

     DBP (mm Hg)

94 (82-105)

94 (89-116)

0.40

     MAP (mm Hg)

115 (108-129)

127 (111-144)

0.30

     O2 Saturation (%)

97 (94-98)

93 (92-96)

0.009

Exercise Hemodynamics

     mPAP (mm Hg)

29.8 (21.5-34.5)

35.0 (32.3-40.3)

0.01

     TPR (WU)

2.3 (1.9-3.3)

3.5 (2.9-5.2)

0.004

     Slope mPAP/CO ratio

1.6 (0.9-2.7)

3.1 (2.6-3.7)

0.01

     R2 for slope

0.63 (0.4-0.8)

0.72 (0.6-0.7)

0.40

     Δ (mPAP/CO) (WU)

2.0 (1.1-3.8)

3.3 (2.7-5.6)

0.009

     RA (mm Hg)

8 (3.5-13.5)

8 (6.0-10.0)

0.90

     PAWP (mm Hg)

17 (9.5-22.0)

15 (12.0-22.0)

0.80

     CO (L/min)

11.7 (9.3-12.9)

10.5 (7.7-11.3)

0.09

     CI (L/min/m2)

6.1 (5.2-6.9)

4.7 (4.2-6.0)

0.045

     TPG (mm Hg)

17.2 (12-22) 

21 (15-26) 

0.08 

     PVR (WU)

1.7 (1.0-1.9)

2.5 (1.7-3.1)

0.021

     Pulse Pressure (mm Hg)

36.5 (29-42)

44.0 (42-50)

0.007

     Stroke volume (mL)

100.8 (84-120)

81.3 (70-111)

0.16

     PA compliance (mL/mm Hg)

2.7 (2.3-3.5)

1.9 (1.3-3.3)

0.019

     PA Saturation (%)

42.1 (37.6-46.1)

42.9 (40.3-45.2)

0.90

Exercise PH Classification

     mPAP>30, n (%)

14 (44)

10 (91)

0.012

     TPR >3, n (%)

12 (38)

7 (64)

0.17

     ePH#, n (%)

11 (34)

6 (55)

0.30

     Slope mPAP/CO ratio > 3, n (%)

7 (23)

6 (55)

0.07

     Δ (mPAP/CO) >3, n (%)

10 (31)

6 (55)

0.30

     ePH combination definition*, n (%)

14 (44)

8 (73)

0.16

# mPAP > 30 mmHg and TPR >3.0

* Either ePH or Slope of the mPAP/CO >3 or Δ (mPAP/CO) >3

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