Pulmonary Hypertension Due to Left Heart Disease

Publication Date: December 1, 2018


Pulmonary arterial wedge pressure 

A value of PAWP >15 mmHg, measured at end-expiration at rest, is considered consistent with PH-LHD. There is insufficient new data since the 5th WSPH in 2013 to recommend a change in this cut-off value.
PAWP should be measured at end-diastole to determine the pre-capillary component of PH-LHD and the calculation of PVR. In sinus rhythm, this corresponds to the mean of the a-wave. In atrial fibrillation, it is appropriate to measure PAWP 130–160 ms after the onset of QRS and before the v-wave.
There are no new data to suggest a change in standards for the measurement of PAWP. Therefore, we continue to recommend the assessment of PAWP at end-expiration, as averaging over of the respiratory cycle would reclassify many post-capillary PH patients to pre-capillary disease with the current PAWP cut-off value.
Best practice suggests that RHC should be performed in stable, non-acute clinical conditions for the differential diagnosis of PH. Proper levelling at the mid-chest and “zero”ing the transducer to atmospheric pressure are critical. Patients should be positioned supine with legs flat and pressures recorded during spontaneous breathing (no breath-hold). Measurements should be repeated in triplicate to obtain values within a 10% agreement.
If PAWP is elevated and the accuracy of PAWP is in question, blood oxygen saturation should be determined in the wedge position. If the PAWP oxygen saturation is <90%, direct LVEDP measurement should be obtained.
The presence of significant, large v-waves should be noted as this strongly suggests LHD regardless of resting PAWP.

Isolated post-capillary PH (IpcPH) vs. combined post-capillary and pre-capillary PH (CpcPH)

After careful consideration of the changes in the general definition of PH, the proposed haemodynamic definition of PH in LHD is: 1) IpcPH: PAWP >15 mmHg and mPAP >20 mmHg and PVR<3 WU; and 2) CpcPH: PAWP >15 mmHg and mPAP >20 mmHg and PVR ≥3 WU.
Beyond a strict haemodynamic definition, other markers of disease may be taken in consideration to better determine a patient's prognosis. These could include an additional haemodynamic marker (e.g. DPG or PAC), cardiopulmonary exercise testing (CPET) profile (level of V′E/V′CO2 (minute ventilation/oxygen uptake) slope, exercise oscillatory ventilation, end-tidal carbon dioxide tension (PETCO2)), indices of right ventricular function and right ventricle/pulmonary artery coupling (compliance and elastance) and biomarkers. In the context of PH due to HFpEF, ST2, a member of the interleukin-1 superfamily, may be complementary to N-terminal pro-brain natriuretic peptide (NT-proBNP).
Given the limitations of pure haemodynamic definitions, future studies should be aimed at developing biomarkers and other non-haemodynamic diagnostics to discriminate IpcPH and CpcPH.

Diagnostic approach and differential diagnosis of pulmonary hypertension (PH) in left heart disease (LHD)

The nomenclature of “PAH with cardiovascular risk factors” should be preferred over any other, to account for their coexistence without suggesting that risk factors may be influencing the cause of the PVD. The role of comorbidities in the disease process of PAH is not demonstrated and remains unclear.
A three-step approach should be followed to perform the differential diagnosis between group 2 PH (mainly HFpEF) and PAH: 1) identification of a clinical phenotype suggesting PH-LHD, 2) determination of a pre-test probability for PH-LHD and 3) haemodynamic characterisation.
Invasive assessment should be performed in patients with intermediate probability of PH-LHD, presence of right ventricular abnormality and when risk factors for PAH/CTEPH coexist.
In patients with a PAWP 13–15 mmHg and high/intermediate probability of PH-HFpEF, provocative testing should be considered to uncover PH due to HFpEF. For technical reasons and reliability of pressure recording, a fluid challenge is preferred over exercise in the approach to differential diagnosis.
PAWP >18 mmHg immediately after administration of 500 mL of saline over 5 min is considered abnormal.
However, how this should impact management is unknown. If PAH-specific therapies are initiated in patients with an “abnormal” response, caution should be exercised, including close monitoring of response and side-effects.

Clinical trials and therapy for PH due to LHD

There is still no multicentre trial that suggests targeting PH-LHD with PAH-specific drugs is beneficial. Therefore, we maintain a strong recommendation against the use of PAH therapies in group 2 PH.
In addition, a safety signal should be acknowledged: 1) the use of sildenafil in the context of PH post-VHD intervention is associated with an increased risk of clinical deterioration and death, and 2) the use of macitentan in CpcPH due to heart failure is associated with an increased risk of fluid retention.
Following the MELODY-1 trial, new standards have been proposed to explore the role of PAH-approved therapies in the context of group 2 PH. If pursued, such trials should be limited to PH due to HFpEF with CpcPH. The agent of choice should ideally be a HFpEF disease-modifying drug. Finally, a proof-of-concept study should be performed first, with safety and tolerability, haemodynamic and/or CPET efficacy end-points.
Vasoreactivity testing is not recommended in patients with PH-LHD, outside of the context of assessment for heart transplantation.

Recommendation Grading




Pulmonary Hypertension Due to Left Heart Disease

Authoring Organization

Publication Month/Year

December 1, 2018

Document Type


External Publication Status


Country of Publication


Inclusion Criteria

Female, Male, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Emergency care, Hospital, Operating and recovery room

Intended Users

Social worker, respiratory therapist, nurse, athletics coaching, nurse practitioner, physician, physician assistant


Assessment and screening, Diagnosis, Prevention, Management, Treatment

Diseases/Conditions (MeSH)

D006976 - Hypertension, Pulmonary, D011660 - Pulmonary Heart Disease


pulmonary hypertension, Left heart disease, arterial hypertension, right ventricle, pulmonary artery, haemodynamic phenotypes, arterial fibrillation, cardiovascular comorbidities