Pulmonary Hypertension (Wang - 8/2/23)

 A recording of this presentation can be viewed HERE.

***

Dr. Helena Wang gave an excellent Grand Rounds this week on Pulmonary Hypertension. It is worth watching!

We currently have at least three patients on our adult medicine service that we are evaluating for this condition after getting a TTE to look at their heart failure status. Pulmonary hypertension is such an interesting intersection between the lungs and the heart and a good opportunity to review basic physiology too! Dr. Wang gave an earlier version of this presentation 2 1/2 years ago, and I felt then, as I did this week, that I could watch it over and over. You can! 

But for those who prefer the written word:

The definition of pulmonary hypertension (pHtn) is simple enough: a mean PAP of > 20mmHg at rest.

Dr. Wang likens the pulmonary artery to something like a six lane highway (think of the 101 going north from Novato into Petaluma). When the lanes decrease from six to two in northern Novato, there is suddenly a lot of congestion, and all the cardiac output has to move through that smaller space at higher pressures. Voila! Elevated PAP.

Pulmonary arterial hypertension is rare, but not that rare, 15-50 cases/million, and more common in people with HIV (regardless of CD4 count or duration), connective tissue disease, and portal hypertension. For patients with any of these diagnoses, should be screened annually for pHtn with an echocardiogram (TTE).

Symptoms of pHtn include dyspnea on exertion, fatigue, edema, bloating, and syncope (obviously pretty non-specific). 

On exam, you can see elevated JVP (check the neck veins!), hear a split S2, and see peripheral edema.

Chest imaging reveals often a dilated R pulmonary artery on CXR, and even sometimes a prominent L pulmonary artery. Also, look for the "banana and egg sign" on CT, in which the aortic arch and the pulmonary artery are a little too close in size for comfort. The aortic arch is the banana; the pulmnoary artery is the egg.

Banana and egg sign (photo credit: CHEST Journal)

Okay, what about the TTE??

Oh, reminds the pulmonologist and the family physician, don't forget to pay attention to the right side of the heart in the echocardiogram! Dr. Wang urged us to scroll down, skip the conclusion,  and look at the text (often the third paragraph). Is the RV big? What is the velocity of the regurgitant jet? What is the TAPSE?

A first hint of pulmonary hypertension on a TTE comes on apical 4 chamber view where the R ventricle shows turbulent flow back into the R atrium

RVSP (right ventricular systolic pressure) is an estimate reported on most echo reports and can be very challenging for the Echo tech to calculate. However, a calculated RVSP>25 is considered HIGH right sided pressure and increases your suspicion for pHtn.

The R ventricle is often very plump and dilated under high pressure (so. . .a big chubby RV on echo is another clue that you might have pulmonary hypertension)

Tricuspid Annular Plane Systolic Excursion (TAPSE): RV contracts in a twisting motion with each contraction as RV shortens. Normal excursion is 1.5cm. If RV is volume overloaded and dilated, cannot squeeze as well, not shortening, TAPSE drops <1.5cm on echo

And finally, right heart catheterization is still gold standard for measuring R sided pressures, but really this should be done after you have done a full evaluation (see below) once you are pretty certain you have primary pulmonary hypertension (WHO Group 1). And, due to changes in insurance, it is no longer required always for diagnosis.

WHO Classification of Pulmonary Hypertension

• WHO Class 1: Pulmonary ARTERIAL Hypertension (pressure goes up, fluid backs up)
• WHO Class 1 has the worst outcome: 5 year survival 61%
• only diagnosed once other causes of pulmonary hypertension are identified and treated
• Seen in patients with HIV (regardless of viral load, duration), connective tissue disease (e.g. scleroderma), and portal hypertension
• All other WHO classes are actually pulmonary VENOUS hypertension (something downstream to the lungs causing poor forward flow, back up of blood, then high pressure on R side of heart). These include
• WHO 2: L heart disease (LV systolic or diastolic dysfunction, valvular disease, s/p TAVR, myxomatous disease)
• WHO 3: bad lung disease or hypoxia (COPD, inadequately treated asthma, ILD, sleep disordered breathing (OSA), OHS, chronic exposure to high altitute, developmental lung disease. Consider high resolution CT (with very thin cuts with and without contrast), home sleep test, pulmonary function tests.
• WHO 4: chronic thromboembolic pulmonary hypertension (small, little tiny chronic). You cannot see this on typical PE protocol CT scan. You need a VQ scan to evaluate chronic thromboembolic disease.
• WHO 5: potpourri

Once Pulmonary Hypertension is identified, the next question is DOES the patient have pulmonary hypertension that is primary or secondary

Ddx pulmonary arterial hypertension (WHO Group 1)

• idiopathic
• heritable (no current gene therapies)
• drug and toxin induced (fen fen, methamphetamines including stimulant medications prescribed)
• connective tissue disease (scleroderma)
• HIV
• portal hypertension
• congenital heart disease
• Schistosomiasis (#1 cause of pulmonary hypertension outside the US)

A quick interruption to review the three types of CT chest you might consider to evaluate the lungs:

• CT angiogram (aka CTA) is a very quick scan from feet to head chasing the dye, itskips very low bases and apices of lungs and should never be used to assess for interstitial lung disease. Great for acute PE asessment.
• A High Resolution CT Chest: much thinner cuts (2mm) than a CTA starting at apices and going all the way to the bases. 
• Very high detail of parenchyma
• Ground glass opacities can be atelectasis vs. ILD--> flip when prone to see if atelectasis resolves while doing high res scan
• CT w/wo contrast (e.g. nodule) 
• can see 4 generations of branches of bronchial tree, but keep in mind that there are 17, so you cannot see filling defects in the small peripheral vessels

Treatment of Pulmonary Arterial Hypertension (PAP)

1. First identify if the patient has any WHO 2-5 diagnoses that may be influencing their pHtn and treat them maximally, then repeat TTE to check for PAP
2. If they still display pHtn on TTE, they now meet criteria for pulmonary arterial hypertension (PAP).
3. Consider pulmonary vasodilator therapy (obviously in conjunction with pulmonologist). These, while still very expensive, are coming down in price. The meds range currently between $40,000 to $100,000 per year.

When to treat Pulmonary Arterial Hypertension?

There is NO specific number for pressure goals. Look at patients functional class, 6 minute walk, and Echo

Treatment goals:

• Functional class: symptoms at rest (class IV), normal (class I): goal is 2 or less
• 6 minute walk test: goal is 400mg in 6 minutes ("please walk as far as you can in 6 minutes", not "as fast as you can walk")
• BNP: can be elevated in R heart strain, goal is normal
• Echo: goal is RV not fat and chubby, decompressed and slender, TAPSE moving nicely

Pulmonary Hypertension Therapy

• Endothelin pathway: block (bosentan (black box liver toxicity, no longer used), ambrisentan, macicentan: side effects: edema, check LFTs, watch for rare malignant facial edema
• Nitric oxide pathway: enhance (sildenafil TID, tadalafil QD, no lab monitoring, can get blue green colorblindness, rare complication anterior ischemic optic neuropathy (sudden blindness one eye, reversible when stop), riociguat (TID, more systemic hypotension)
• Prostacyclin pathway: enhance (potent, short half life and unstable)
• epoprostenol: IV infusion, tubing connected to a pump, best mortality data, very labor intensive
• treprostinil: IV vs. sq (like insulin pump) and inhaled QID (takes a lot of time, breathing treatment like nebulizer, 20-30 minutes per treatment
• iloprost: inhaled 6-9 times/day
• selexipag: oral BID, no labs but unrealistic uptitration protocol

Guidelines for treatment are based on functional class. The ultimate goal is minimal symptoms with regular activity

If functional class IV-->  needs prostacyclins right away

If functional class III-->  can start with orals (e.g. tadalafil and macicentan)

Any questions? Email or staff message Dr. Helena Wang at: helena.wang@sutterhealth.org