Pulmonary Hypertension (Wang, 1/13/2021)

Dr. Helena Wang gave an excellent Grand Rounds this week on Pulmonary Hypertension. 

You know when you have read about a particular topic a hundred times and you still don't quite grasp even the most basic of concepts? Well, that is pretty much how I have felt about pulmonary hypertension for the last decade. I get all tangled up in the RVSP and the strange WHO Classifications and have never quite been able to solidify my illness script for pulmonary hypertension. 

Well, Dr. Wang, thank you. I feel like I am finally here. Pulmonary hypertension is such an interesting intersection between the lungs and the heart and a good opportunity to review basic physiology too! As one of our residents said to me yesterday after the talk, " I feel like hers is a presentation I want to watch again and again." Me too (and I did!). For those of you who want the written summary, here goes:

First a refresher on Pulmonary Function Tests (PFTs):

• The FEV1/FVC Ratio should be used to determine if a patient has an OBSTRUCTIVE lung disease. 
• Remember that an FEV1/FVC <70% is consistent with an obstructive disorder (e.g. asthma, COPD, etc)
• Total Lung Capacity (TLC) is used to decide if a patient has a RESTRICTIVE lung disease
• 80-120% is considered normal 
• Patients with restrictive lung disease will have a TLC <80%
• Diffusion capacity for carbon monoxide (DLCO) provides information on the efficiency of gas transfer from alveolar air into the bloodstream
• for these defects in gas exchange, ddx includes pulmonary hypertension and liver disease

Second, reminds the pulmonologist, don't forget to pay attention to the right side of the heart in the echocardiogram!!  Dr. Wang urged us to scroll down and look at the text. 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
• First they measure the velocity of tricuspid regurgitant jet (velocity >3 is a clue that there may be pulmonary hypertension present)
• then they guestimate of CVP (0, 5, 10) based on compressibility of IVC
• NOTE: a calculated RVSP>25 is considered HIGH right sided pressure
• 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 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)

WHO Classification of Pulmonary Hypertension

• WHO Class 1: Pulmonary ARTERIAL Hypertension (it's like going from a 6 lane highway down to a 2 lane highway--> pressure goes up, fluid backs up)
• WHO Class 1 has the worst outcome: 5 year survival 61%
• only once other causes of pulmonary hypertension are identified and treated
• Seen in HIV (regardless of viral load, duration), Connective tissue disease (e.g. scleroderma), 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
• WHO 3: bad lung disease or hypoxia
• WHO 4: chronic thromboembolic pulmonary hypertension (small, little tiny chronic)
• 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)

Ddx WHO Group 2: a bad heart

• left heart disease: LV dysfunction (systolic and diastolic), valvular dz, outflow obstruction

Ddx WHO group 3: bad lungs

• asthma and COPD (need PFT: spirometry, lung volumes, diffusion capacity)
• ILD (need HIGH resolution CT chest)
• sleep disordered breathing (episodic hypoxia at night causes vasospasm), need sleep study
• chronic high altitude
• developmental lung dz

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
• 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

Ddx WHO group 4: chronic thromboembolic pulmonary hypertension (itty bitty clots on VQ scan)

• need VQ scan to get the level of detail in microvasculature

Ddx WHO group 5: potpourri

• hematological disorder (myeloproliferative)
• systemic disorders (sarcoid, LAM--> chylothorax)
• glycogen storage disorder
• thyroid disorders
• chronic renal failure
• mechanical (fibrosing mediastinitis, tumoral obstruction)

Right heart catheterization

Once you have maximally treated all WHO 2-5 diagnoses, treat as aggressively as possible (e.g. diastolic dysfunction, COPD/asthma, chronic clots, sleep apnea, etc), then you repeat ECHO and see if there is still elevated pressure on R side of heart--> NOW, patient should get a right heart cath to confirm exactly what the pressure is.

• On A R heart cath, PA pressure normal <25/15
• Mean PA pressure normal is <25
• Pulmonary hypertension = mean pressure >25

• Gold standard is also to do a vasodilator challenge during R heart cath to see if there is reversible spasm in the pulmonary arteries? (inhaled nitrous oxide, epoprostenol, or adenosine--> look for decreased pressure)
• if PA pressure decreases by 10 mmg HG, ending pressure <40, no drop in cardiac output
• less than 10% of patients have + response to vasodilator
• calcium channel blockers are treatment of choice for those who do have vasospasm

When to treat Pulmonary Arterial Hypertension?

There is NO 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")
• 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 nonarterici 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: wanghl@sutterhealth.org