Reply to Olschewski et al.

From the Authors:

In their letter “Let’s Talk about Respiratory Swings!” Olschewski and colleagues highlight the importance of precision and accuracy around hemodynamic measurements, particularly pulmonary arterial wedge pressure (PAWP) reporting. We agree that there is room for clarity in future pulmonary hypertension (PH) guidelines and that the current convention of reading values at end-expiration, especially in certain patient scenarios such as obesity and chronic lung disease, should be reconsidered. As written, current guidance to perform all pressure measurements at end-expiration, with allowance for reporting average PAWP in patients with “large” respiratory swings, is ambiguous and subject to inconsistency across operators, with downstream consequences on PH diagnosis, disease phenotyping, and treatment eligibility (1, 2). This is particularly problematic for a procedure already limited by operator misinterpretation. In fact, inappropriate PAWP reporting is identified even at expert PH centers (3).

The treatment of patients with PH has become more complex, with many beneficial therapies now available, as discussed in our recent state-of-the-art paper (4). These benefits are opposed by risk of harm if therapies are used inappropriately (5, 6). As novel therapeutics are tested within and outside of pulmonary arterial hypertension, standardized enrollment in clinical trials is essential. For example, in a patient with significant respirophasic variation with an end-expiratory PAWP of 16 mm Hg but a mean PAWP of 12 mm Hg, the use of end-expiratory PAWP would result in exclusion from a study of pulmonary arterial hypertension but may instead result in enrollment in a trial of combined pre- and postcapillary PH (4). This may limit generalizability to a presumed “combined pre- and postcapillary PH” population. Furthermore, reporting the higher end-expiratory PAWP would decrease the transpulmonary gradient and therefore the calculated pulmonary vascular resistance ([mean pulmonary arterial pressure − PAWP]/cardiac output), potentially limiting eligibility for any trial enrollment. Work by Khirfan and colleagues further demonstrates the impact of PAWP reporting on disease classification (7). These authors described the impact of accounting for intrathoracic pressure measurements when performing right heart catheterization within an obese cohort (body mass index ⩾ 30 kg/m²). Subtraction of intrathoracic pressure measurements, or esophageal pressure, assessed via concomitant esophageal balloon placement, significantly decreased the proportion of patients classified as having isolated postcapillary PH.

In patients with chronic obstructive pulmonary disease (COPD)–PH, mortality risk among patients with pulmonary vascular resistance > 5 Wood units is newly appreciated (8). Anticipating future clinical trial enrollment for this population, consistency around average PAWP reporting will be particularly relevant. In fact, additional work using esophageal balloons to assess transmural pressure in a COPD population confirms the overestimation of PAWP at end-expiration in patients with COPD–PH (9).

Although it is not feasible to scale transmural pressure measurements, careful hemodynamic studies such as those performed by Olschewski and colleagues and others help challenge conventional thinking. As we enter a contemporary era of PH phenotyping and our pharmaceutical armamentarium expands, we support Olschewski and colleagues’ suggestion to the PH community to use averaged PAWP values. We also suggest consideration of stipulating clinical trial enrollment criteria on the basis of mean PAWP to ensure precision and accuracy across multicenter studies.