#294 Pulmonary Hypertension Update

September 13, 2021 | By Deb Gorth

Join us as we take a six-minute walk through the definition, presenting symptoms, and diagnosis of pulmonary hypertension with our esteemed guest Dr. Estefania Oliveros, @EstefaniaOS (Temple University). She helps us get on the right side of hypertension on the right side of the heart!

New to pulmonary hypertension? Check out our prior episode #80: Pulmonary Hypertension, freeways, and cows in heart failure with Dr. John Ryan that sets up the framework for how to think about the initial diagnosis of pulmonary hypertension.

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Credits

• Writer and producer: Deborah Gorth MD, PhD
• Infographic and Cover Art: Edison Jyang
• Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP   
• Reviewer: Leah Witt, MD
• Editor: Matthew Watto MD (written materials); Clair Morgan of nodderly.com
• Guest: Estefania Oliveros MD 

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Show Segments

• Intro, disclaimer, guest bio
• Guest one-liner
• Picks of the Week
• Case from Kashlak
• Definitions
• Discussion of testing for pulmonary hypertension
• CTEPH diagnosis and management
• Rundown of therapies for pulmonary hypertension
• Outro

Pulmonary Hypertension Pearls

1. Pulmonary hypertension (PH) is an increase in the pulmonary arterial pressure (defined as a mPAP > 20 mmHg (Simonneau, 2019)) caused by numerous underlying pathologies. 
2. PH is divided into five groups: group 1 (pulmonary arterial hypertension), group 2 (left heart disease), group 3 (lung diseases and/or hypoxia), group 4 (chronic thromboembolic pulmonary hypertension and pulmonary artery obstructions), and group 5 (multifactorial mechanism). 
3. The pulmonary arterial wedge pressure (PAWP) is a surrogate for what is happening on the other side of the septum (the left ventricular end diastolic pressure) during a right heart cath and can be used to differentiate pre-capillary and post-capillary PH.
4. The presenting symptom of PH can be a non-specific combination of fatigue and shortness of breath. In severe PH, syncope can be the first presenting symptom..
5. A V/Q scan is the gold standard for ruling out CTEPH (Tunariu, 2007).
6. Pulmonary hypertension due to cardiac and pulmonary conditions can be ameliorated by addressing the underlying condition; PH secondary to heart failure should be managed with diuretics, and oxygen therapy can be useful in patients with PH caused by lung pathologies (ESC/ERS Guidelines).
7.  Sildenafil, tadalafil, and riociguat cannot be taken with nitrates!

Pulmonary Hypertension

This is an update of our January 2018 episode, #80: Pulmonary Hypertension, freeways, and cows in heart failure. 

Definition

Pulmonary hypertension (PH) is increased pulmonary arterial pressure. This increase in pressure can occur due to numerous underlying pathologies. To delineate these different etiologies, pulmonary hypertension is divided into five groups (Simonneau et al 2019):

Group 1 Pulmonary arterial hypertension (1.1 idiopathic PAH,1.2  heritable PAH, 1.3 drug/toxin induced PAH, 1.4.1 PAH associated with connective tissue disease, 1.42 HIV, 1.4.3 portal hypertension, 1.4.4 congenital heart disease, 1.4.5 schistosomiasis,  1.5 long term responders to calcium channel blockers, 1.6 PAH with features of venous/capillaries involvement, 1.7 persistent PH of the newborn)

Group 2 PH due to left heart disease (2.1 preserved LVEF, 2.2 reduced LVEF, 2.3 valvular heart disease, 2.4 congenital/acquired cardiovascular conditions with post-capillary PH) 

Group 3 PH due to to  lung diseases and/or hypoxia  (3.1 obstructive lung disease, 3.2 mixed restrictive/obstructive lung disease, 2.4 hypoxia without lung disease, 3.5 developmental lung disease)

Group 4 PH due to pulmonary artery obstructions (4.1 chronic thromboembolic PH (CTEPH), 4.2 other pulmonary artery obstructions)

Group 5 PH with unclear and/or multifactorial mechanisms (5.1 haematological disorders, 5.2 systemic and metabolic disorders, 5.3 others, 5.4 complex congenital heart disease)

Pulmonary hypertension was initially defined as a mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest, measured during a right heart catheterization. This value was set arbitrarily at the 1st World Symposium on Pulmonary Hypertension in 1973. Recent data showed that the average mPAP in the general population was 14 mmHg (Kovacs et al 2009). Using two standard deviations above this value (an evidence based threshold) the 6th World Symposium on Pulmonary Hypertension changed the haemodynamic definition of pulmonary hypertension (PH) to a mPAP > 20 mmHg (Simonneau et al 2019). The values of pulmonary arterial wedge pressure (PAWP) and pulmonary vascular resistance (PVR) are two additional values that help define PH. 

Pulmonary arterial wedge pressure (PAWP) is the end expiratory pressure obtained by a catheter “wedged” in a pulmonary vein with a balloon inflated to isolate the sensor from the venous pulmonary blood flow. This lets the catheter measure just the pre-capillary pressure. The wedge pressure is a surrogate for what is happening on the other side of the septum (the left atrium) during a right heart cath and can be used to differentiate pre-capillary and post-capillary PH.

Pulmonary vascular resistance (PVR) is defined using wood units, the hydraulic equivalent (pressure gradient/pulmonary blood flow) of electrical resistance (voltage/current) aka ohms (Kwan et al 2019), but Dr. Oliveros says that it is easier to think about it as the pressure you would feel if you put your finger in a hose with running water. 

Pulmonary hypertension can also be thought of as two large groups, pre-capillary and post-capillary. Post-capillary pulmonary hypertension, the most common form of PH, is caused by elevated pressure due to left sided heart disease, causing a backup of blood and elevated right sided pressures.  

 Pre-capillary PH is increased pressure of pulmonary arterial system in the absence of elevated left-sided pressure.  If the PAWP is ≤ 15 mmHg it is pre-capillary PH (Group 1, 3, 4, and 5). If PAWP is > 15 mmHg and PVR < 3 wood units, it is isolated post capillary PH (Group 2 and 5). If PAWP is > 15 and PVR ≥ 3 wood units it is combined pre-and post-capillary PH (Group 2 and 5) (Simonneau et al 2019). Despite this extensive classification system, patients often transcend specific pulmonary hypertension groups. 

Signs and symptoms of pulmonary hypertension

History 

The key to diagnosing PH, like any disease, is taking a good history. The presenting symptom of PH can be a non-specific combination of fatigue, shortness of breath, and even syncope with severe pulmonary hypertension. For a patient presenting with dyspnea and fatigue, it is important to get a sense of how long these symptoms have been an issue, if the symptoms are getting worse, and equally as important, if these symptoms occur at rest or only with exertion.

Symptoms like orthopnea (shortness of breath lying flat) or bendopnea (shortness of breath bending over) can indicate underlying heart failure, which could cause Group 2 PH. Wheezes and dry cough can point to lung conditions (Group 3 PH).  A history of PE and or familial clotting disorders should make you consider CTEPH (Group 4 PH) (Pengo et al 2004). Rashes, a family history of autoimmune disorders, joint pain, Raynaud’s, or dysphagia (CREST symptoms) can indicate connective tissue disease or systemic disorders linked with PH. Additionally, numerous drugs and toxins are associated with PH, including methamphetamines (Zamanian et al 2018). 

Physical Exam

The physical exam findings for suspected PH should include both a thorough cardiovascular exam, and a systemic exam to look for signs of conditions linked to PH. PH can include heart sounds with a normal S1 and an accentuated S2 (the pulmonic valve component), tricuspid regurgitation (a systolic murmur best heard on the left parasternal border), and the jugular venous pressure (JVP)–Dr. Oliveros thinks turtle necks should be banned!. Tachycardia is a concerning finding potentially indicating decompensated disease. The physical exam can also suggest an underlying cause for PH. Rashes, telangiectasia, digital clubbing, and inspiratory crackles can suggest underlying systemic, hepatic or pulmonary processes that can cause PH (ESC/ERS Guidelines).

Testing for pulmonary hypertension

A right heart catheterization is required to confirm a diagnosis of PAH. The workup recommended for PH includes many common tests that you would typically order to evaluate fatigue and shortness of breath: ECG (to look for right heart hypertrophy), chest x ray (which could show pulmonary arterial dilation, right atrial enlargement, or parenchymal lung disease, though if this is strongly suspected a CT chest would better assess lung parenchyma), pulmonary function tests/overnight oximetry (to identify lung pathologies, group 3 PH), echocardiography (to look for left sided heart pathologies), CBC (which can show anemia, another cause of shortness of breath), platelets (some have hypercoagulability), LFTs, TSH (both hypothyroid and hyperthyroid can cause PH), and a V/Q scan (to rule out CTEPH)(ESC/ERS Guidelines).

V/Q scan for CTEPH

A V/Q scan is the gold standard for ruling out CTEPH. The negative predictive value of V/Q scan for CTEPH is nearly 100% (Tunariu et al 2007). When ordering a V/Q scan, you need both the ventilation and perfusion portions to evaluate for CTEPH; an elevated diaphragm without a ventilation scan can cause a false positive. A V/Q scan suggestive of CTEPH would show an unmatched defect in perfusion. European CTEPH registry observed that median time from presentation to diagnosis for CTEPH was 14.1 months (Pepke-Zaba et al 2011). While this is an exceedingly rare diagnosis, if caught, it is treatable with referral to an expert center for a specialized surgery to mechanically remove the clot (Mahmud et al 2018).

Treatments

Pulmonary hypertension due to cardiac and pulmonary conditions can be ameliorated by addressing the underlying condition; PH secondary to heart failure should be managed with diuretics, and oxygen therapy can be useful in patients with PH caused by lung pathologies (ESC/ERS Guidelines). While PH specific drug therapies should be prescribed by PH specialists, it is important to understand the side effect profiles and specific considerations of PH treatments. These treatments should be continued even in hypotensive patients with PH. Stopping these medications can cause rebound pulmonary hypertension leading to right sided heart failure. 

Kashlak Pearl: Stopping pulmonary hypertension medications can cause rebound pulmonary hypertension leading to right sided heart failure. 

PDE type 5 inhibitors (sildenafil/tadalafil) can cause headaches, which can be typically managed with acetaminophen. These medications can also lead to hypotension, so consider this impact on blood pressure while prescribing hypertension medications. Importantly, sildenafil and tadalafil cannot be taken with nitrates (isosorbide/nitroglycerin/nitroprusside/amyl nitrite), or they will cause profound life threatening hypotension. 

Endothelin receptor antagonists (ambrisentan/bosentan/macitentan) can cause nausea, diarrhea, fluid retention and liver toxicity, so liver function tests should be monitored every 3 months. 

Prostacyclin analogs (epoprostenol/treprostinil) can cause local erythema and induration at the injection site. This can look like cellulitis. 

The guanylate cyclase stimulator riociguat cannot be taken with nitrates (isosorbide/nitroglycerin/nitroprusside/amyl nitrite) due to the same synergistic hypotension of PDE type 5 inhibitors. 

Links

1. Daughter of Fortune by Isabel Allende. 
2. Say Nothing by Patrick Radden Keefe
3. Nobody (Paul’s movie recommendation)
4. American Gods by Neil Gaiman

Goal

Listeners will learn the basic pathophysiology, workup, and management of pulmonary hypertension to improve diagnosis and partnership with specialists. 

Learning objectives

After listening to this episode listeners will…

1. Define pulmonary hypertension
2. Learn the classification schema for pulmonary hypertension
3. Recognize the components of a patient history suggestive of pulmonary hypertension
4. Develop a diagnostic approach to patients presenting with symptoms concerning for pulmonary hypertension
5. Appreciate the importance of screening for chronic thromboembolic pulmonary hypertension
6. Learn the therapies available for different etiologies of pulmonary hypertension
7. Recognize when to refer a patient with pulmonary hypertension to an expert center
8. Become familiar with the special concerns for hospitalized patients with pulmonary hypertension

Disclosures

Dr Oliveros reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Gorth DJ, Oliveros E, Williams PN, Witt L, Watto MF. “Pulmonary Hypertension Update with Estefania Oliveros”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date September 13, 2021.