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DEFINITIONS - There are five subtypes of pulmonary hypertension (PH) in the most recent classification from the 5th World Symposium on Pulmonary Hypertension in 2013.¹ Group 1 is typical pulmonary arterial hypertension (PAH), and group 2 is PH due to left heart disease. Group 2 PH is the most common subtype encountered in clinical practice, including in the stress echocardiography laboratory.

Pre-capillary PH is invasively defined as a mean pulmonary artery pressure (PAP) >25 mmHg at rest, pulmonary capillary wedge pressure (PCWP) <15 mmHg, and a calculated pulmonary vascular resistance <3 Wood units.² It is distinguished from post-capillary PH in which PCWP is >15 mmHg. Mean PAP of 25 mmHg approximates a right ventricular systolic pressure of 38 mmHg.

Despite this apparently clear subdivision, there may be phenotypic continuum between these groups.^3,4 In 2013, Vachiéry et al. proposed subdivision of PH due to left heart disease into 2 categories on the basis of the diastolic pressure difference (DPD).⁵ DPD = diastolic PAP – mean PCWP. Isolated pre-capillary PH was defined as PCWP >15 mmHg and DPD <7 mmHg. Combined pre- and post-capillary PH was defined as PCWP >15 mmHg and DPD ≥7 mmHg. This sub-classification was incorporated into the most recent European guidelines.²

Invasive criteria for diagnosis of exercise-induced PH have been proposed,⁶ but there are limited exercise echocardiographic data concerning standards for right atrial pressure (RAP) and PAP⁷ and their prognostic implication. Consequently, both the 5th World Symposium on Pulmonary Hypertension¹ and European Society of Cardiology²guidelines discourage the use of the term exercise-induced pulmonary hypertension. Therefore, making a diagnosis of PH during stress echocardiography is challenging because specific, validated, consensus diagnostic criteria do not exist.

The preferred test to assess PAP with exercise is supine bike ergometry. This allows for sequential assessment of pulmonary pressures at progressively higher workloads, usually at 2-3 minute intervals. Less optimally, treadmill exercise testing can be performed with pressure assessments, done preferably within 1-2 minutes post-exercise. PAP is then calculated using peak tricuspid regurgitant velocity (TRV) and estimated RAP in the modified Bernoulli equation: 4(TRV)² + RAP.⁸Because the TRV is squared, minimal measurement error leads to disproportionately higher error in the estimated PAP.

UNDERESTIMATION OF PULMONARY PRESSURE - TRV should be measured in multiple views, parallel to the color Doppler tricuspid regurgitation signal because it is angle dependent. RAP is estimated based on standard criteria using inferior vena cava size and degree of inspiratory collapse.⁹ However, this assumes constant RAP at rest and exercise. RAP may be significantly increased at high workloads, particularly in patients with heart failure.⁷ This may cause underestimation of exercise PAP. TRV may not truly reflect right ventricle/right atrium pressure gradient in cases of severe tricuspid regurgitation due to rapid equalization of pressures.

OVERESTIMATION OF PULMONARY PRESSURE - Exercise right ventricular systolic pressure may be overestimated by incorrect measurement of tricuspid regurgitation signal. A full modal signal with a clear peak, rather than weak or incomplete signals, must be used. Administration of agitated saline or contrast agents can be quite useful in improving signal intensity and measurement accuracy. TRV may be overestimated by measurement of contrast artifacts.

PAP is also higher in athletes, especially at high workloads, compared with normal non- athletic controls. These differences are due to higher levels of cardiac output and left ventricular filling pressures.^12,13 A cut-off exercise PAP of 60 mmHg has been suggested for athletes.⁷ PAP also increases with each decade of life, possibly due to non-flow mediated increases in pulmonary vascular resistance.^14,12 In individuals >50 years, resting PAP may be as high as 40 mmHg. PAP is also higher in obese patients. The 2017 recommendations from the European Association of Cardiovascular Imaging and the American Society of Echocardiography suggest a threshold of PAP ≥60 mmHg during exercise stress echocardiography. A threshold of TRV of 3.1 m/sec or PAP >43 mmHg generally applies in young, healthy individuals.¹³

Patients at risk for PAH, such as first-degree relatives of PAH patients and patients with connective tissue disease, sickle cell disease, and human immunodeficiency virus, may also have abnormal exercise PAP; screening should be considered in these groups.^7,13,16

^{KEY POINTS}

• + There are no validated diagnostic criteria for PH during exercise.
• + The term exercise-induced pulmonary hypertension should generally be avoided.
• + Careful attention to study quality, including signal acquisition and measurement, is needed to prevent overestimation or underestimation of PAP.
• + TRV is higher in 5-10% of normal outliers, patients over 50 years of age, obese individuals, and elite athletes.
• + Except in the above-stated conditions, TRV >3.1 m/sec and estimated PAP >43 mmHg may be abnormal and prompt further evaluation.
• + PH during stress echocardiography may be seen in pathologic conditions such as high-flow states, HFpEF, and valvular heart disease.
• + PH seen during stress echocardiography is most commonly due to left heart disease.
• + PH during stress echocardiography may be seen in patients at risk of or with subclinical PAH.
• + Routine addition of diastolic function and PAP assessment to standard stress echocardiography testing can provide incremental clinical particularly in patients with exercise-limiting or unexplained dyspnea and reduced exercise capacity.
• + Further research and validation studies are needed for the development of specific guidelines for the diagnosis of PH during stress echocardiography.

REFERENCES

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