Pulmonary arterial hypertension with below threshold pulmonary vascular resistance

Abstract

<jats:p>Pulmonary vascular resistance (PVR) &gt;3 Wood units is a criterion of the haemodynamic definition of pulmonary arterial hypertension (PAH). However, this cut-off is conservative and arbitrarily defined. Data is lacking on the natural history, response to therapy and survival of patients diagnosed with precapillary pulmonary hypertension (PH) with mild or borderline elevation of PVR.</jats:p><jats:p>In Australia, PAH therapy could be prescribed solely on mean pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) criteria. Using the Australian and New Zealand Pulmonary Hypertension Registry, we aimed to study a population diagnosed with PAH between January 2004 and December 2017 with the pre-defined haemodynamic characteristics of mean PAP ≥25 mmHg, PAWP ≤15 mmHg and PVR &lt;3 Wood units.</jats:p><jats:p>Eighty-two patients met the pre-defined haemodynamic inclusion criteria (mean age 63±11 years; 67 females). Underlying aetiologies included idiopathic disease (n=39), connective tissue disease (CTD; n=42) and HIV infection (n=1). At diagnosis, mean PAP was 27 mmHg (interquartile range (IQR) 25–30 mmHg), PAWP 13 mmHg (IQR 11–14 mmHg) and PVR 2.2 Wood units (IQR 1.9–2.7 Wood units). Baseline 6-min walk distance (6MWD) was 352 m (IQR 280–416 m) and 77% of subjects were in New York Heart Association (NYHA) functional class 3 or 4. All patients were commenced on initial monotherapy with an endothelin receptor antagonist (ERA; n=66) or phosphodiesterase type-5 inhibitor (PDE5i; n=16). At first re-evaluation, 6MWD increased by 46 m (IQR 7–96 m) and 35% of subjects demonstrated improvement in NYHA functional class. After a median follow-up of 65 months (IQR 32–101 months), 18 out of 82 subjects (22.0%) had died, with estimated 1-year and 5-year survival rates of 98% and 84%, respectively. Death attributed to PAH occurred in six out of these 18 patients (33.3%, 7% of total cohort).</jats:p><jats:p>Patients with precapillary PH and “borderline” PVR falling outside the current definition have adverse outcomes. Such patients appear to respond to PAH therapy; however, this requires further study in randomised trials.</jats:p>

Mild pulmonary hemodynamic alterations in patients with systemic sclerosis: relevance of the new 2022 ESC/ERS definition of pulmonary hypertension and impact on mortality

“…When patients with normal or only mildly elevated PVR were excluded, we did not observe a difference in relationship between PVR and CI in patients with SSc-PAH suggesting that increased stiffness of the pulmonary arterial bed is unlikely to be responsible for differences in outcomes. The patients with PVR between 2 and 3 also appear to be at risk of progression to PH [ 21 ], which seems to be also observed in our cohort.…”

Adding an important piece to the pulmonary vascular resistance puzzle in pulmonary arterial hypertension

“…Results extrapolated from this study could also be used to guide national screening programmes for detecting early stage PAH, already underway in some countries, including France [13]. RATWATTE et al [9] are to be congratulated on these important data, which help build a much-needed framework for contemporising the PAH haemodynamic criteria relative to PVR. These findings should stimulate additional investigations using definitive clinical research methodologies, which were not yet available at the time the current work was assembled, to understand the association between PVR <3.0 WU and therapeutic response in PAH.…”

“…In this issue of the European Respiratory Journal, RATWATTE et al [9] add a key piece to the PVR puzzle by leveraging the unique clinical practice patterns in Australian and New Zealand, in which PVR ⩾3.0 WU is not obligatory for treating PAH. The investigators assembled data for 2378 PAH patients enrolled in the PHSANZ registry between 2011 and 2018, and focused on 82 patients for whom the PVR was <3.0 WU.…”

Pulmonary hypertension phenotypes in patients with systemic sclerosis

“…JAAFAR et al ) who were all treated with PAH-specific therapy. They found that this haemodynamic picture was associated with impaired function and reduced survival but was also associated with functional response to PAH-specific therapy [79].…”

“…In those patients with a mPAP ⩾19 mmHg and PAWP ⩽15 mmHg, the PVR threshold above which the hazard ratio for mortality increased was 2.2 WU. RATWATTE et al[79] recently presented data on 82 patients (42 with CTD) with mPAP ⩾25 mmHg, PAWP ⩽15 mmHg but PVR <3 WU (median (interquartile range) 2.2 (1.9-2.7) WU…”