Grand Rounds – 9/30/22 – Pulmonary Hypertension Updates

Last week in Grand Rounds, 3rd year fellow Romy Lawrence treated us an update on the latest advances in Pulmonary Hypertension.

The graphic below provides a helpful organizer for the three physiologic categories of PH: pre-capillary (Pre-PH), combined pre-and-post capillary (Cpc-PH), and isolated post-capillary (Ipc-PH)

Another common characterization for PH is WHO category. As a reminder of categories:

• 1: PAH
• 2: 2/2 left heart disease
• 3: 2/2 lung disease
• 4: CTEPH
• 5: Other/misc

 

I. Updates in PH definitions

First, how did the 2022 ESC/ERS update change from the 2018 WSPH Guidelines?

The PVR cutoff was changed to 2! This was decided as it was roughly the cutpoint above which an increased hazard ratio for mortality was observed in the CART cohort. An important point here – these do not yet translate to therapeutic recommendations, as efficacy of PH therapy between mPAP 21-24 and 2-3 WU remains unknown. 

So if the new cutoffs haven’t resulted in updates in therapeutic recommendations, what do we do with them??

 

The entity of exercise PH, defined as a mPAP/CO slope between rest and exercise >3 Hg/L/min, was also defined.

A really important point here – symposia have been exclusively held in affluent countries, despite the fact that most of the global PH burden is in low and middle income countries. What implications does this have for focus of therapeutics, imaging, advocacy?

 

 

II. Pulmonary hypertension therapeutics:

Here’s a broad overview by WHO group:

Romy reminded us that the mainstay of PAH therapy is to target one of three pathways known to be implicated in the pathogenesis of PAH: (1) excessive endothelin-1 production, (2) deficient prostacyclin, and (3) low nitric oxide production.

After vasoreactivity testing and CCB trial if applicable, the most important determinant of treatment is risk assessment (REVEAL score or ESC/ERS risk stratification). An algorithmic approach from there:

The risk calculator is linked below if you’d like to learn more!

 

 

III. PAH in pregnancy

PAH in the pregnant woman – an uncommon situation with extremely high (30-50%) mortality. The WHO recommends against pregnancy in PAH. We also discussed the following:

• Patients should be counseled around risk and provided contraceptive advice
• Referral to a PH center if patient considering becoming pregnant and/or if pregnant and considering termination for maternal safety
• ERAs (macitentan, bosentan, ambrisentan) are teratogenic

 

IV. Chronic thromboembolic pulmonary hypertension (CTEPH)

3 criteria for CTEPH:

• mPAP >20
• PCWP <15
• Evidence of chronic perfusion defects after 3 mo anticoagulation

What is the relationship between acute PE and onset of CTEPH?

Important to know that certain factors increase the likelihood of CTEPH. These include some unsurprising conditions, such as prior PE (OR 19) especially unprovoked (OR 5.7).

Less intuitive – splenectomy (OR 18), ventriculo-atrial shunt or infected pacemaker (OR 76!!)

Finally, an overview of CTEPH treatment pathways:

Balloon pulmonary angioplasty (BPA) is used in distal or surgically inaccessible disease, and/or in patients for whom comorbidities preclude surgery. This is done in series of 4-6 sessions separated in time by several weeks.

Riociguat is approved for use in medical management of inoperable CTEPH based off of the CHEST trials.

The role of medical therapy as a bridge to surgery or BPA is less certain, given that it may delay appropriate referral and expedited treatment.

 

 

A few take home points from the discussion.

Thanks for an outstanding Grand Rounds, Romy!

Sources

• Humbert et. al. ESC/ERS Guidelines 2022
• Maron et. al Lancet 2021
• Auger et al. Clin Chest Med 31 (2010) 741–758
• Bonderman D et al. Thromb Haemost 2005;93:512-516
• Humbert M.  Eur Respir Rev 2010; 19: 115, 59–63
• Pengo V et al. New Engl J Med 2004;350:2257-2264
• Ghofrani, HA. D’Armini, AM., et. al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013.
• Jais, X., D’Armini, AM., et. al. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension” BENEFiT. J Am Coll Cardiol . 2008.
• Ghofrani, HA, Simonneau, G., et. al. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension. (MERIT-1): Lancet Respir Med 2017.
• https://pahriskcalculatorre.com/