Pulmonary Hypertension

Pulmonary hypertension is a rare disease that progressively affects the pulmonary vasculature and subsequently the heart. The initial insult is the pulmonary vasculature; but the survival is closely related to the heart, specifically in the RV function.

Pulmonary hypertension is simply a mPAP>25. It is broad group with many facets underneath it. It can be caused by increased pulm vascular resistance, pulmonary artery stiffness, left atrial HTN, incr pulm blood flow, and combinations thereof.

• 15-50 cases per 1 million people

• REVEAL Registry - US registry of PAH (~3000 patients), 4:1 female predominance

Diagnosis

It is hard to diagnose and is often diagnosed very late - it takes a high level of suspicion to diagnose early. To diagnose pulmonary hypertension you must do a right heart cath (RHC); doing this you will get these values:

• Mean arterial pulmonary artery pressure (mPAP)

  • mPAP = 1/3 systolic PAP + 2/3 diastolic PAP

• Pulmonary artery occlusion pressure (PaOP/wedge pressure) = RHC or swan, a surrogate for your LAP

• Pulmonary Vascular Resistance = you must calculate it

  • Normal: <2

  • PVR = mPAP - wedge pressure/CO (unit: woods)

Types of PH

• Group 1 : Pulmonary arterial hypertension is a diagnosis of exclusion. It is type of pulmonary hypertension but not all PH patients have PAH; you must exclude group 2-5.

  • mPAP <25 + PVR >3 woods units + wedge <15, excluding other cause

  • Generally their PVR will be pretty high (5-6 wood units compared to ~3 in other causes)

    1. Idiopathic PAH, Heritable PAH (BMPR2, ALK1, CAV1, etc), drug and toxin induced PAH

    2. Associated with CTD, HIV, portal HTN, congenital heart diseases, shistosomiasis (uncontrolled HIV esp)

       1. Very difficult to differentiate primary PAH in cirrhotics vs high PAH due to increased volume/high CO; important issue, must have mPAP<35 for transplant

• Group 2 - Pulmonary hypertension due to left heart disease

  • Pulmonary venous hypertension (PVH) is by far the most common cause PH. It is especially important to differentiate patients with PH due to left heart congestion from patients with PVD; the diagnostic and treatment strategies differ.

    • wedge>15

  • LV systolic dysfunction, diastolic dysfunction

  • Valvular disease; Congenital/acquired left heart inflow/outflow obstruction

• Group 3 - PH due to lung diseases and/or hypoxia

  1. COPD, ILD, Other pulmonary diseases w/mixed restrictive and obstructive pattern

  2. Sleep disordered breathing (i.e. OSA), alveolar hypoventilation disorders, chronic exposure to high altitude, developmental lung diseases

  3. To Exclude: check PFTs, alpha 1, sleep study

• Group 4 - chronic PE (CTEPH)

  • To exclude: V/Q scan

• Group 5 - Idiopathic - unclear multifactorial mechanisms

  • Heme d/o, systemic d/o (sarcoidosis/vasculitis), metabolic d/o (thyroid), chronic renal failure and more

  • To exclude: super difficult. Liver serologies and more

But can you have multiple types of pulmonary hypertension?

A good way to think of this is by thinking of pulmonary hypertension as pre-capillary and post-capillary. You can check a diastolic pulmonary gradient (DPG) by looking at your pulmonary diastolic pressures and your wedge pressures. If the difference is minimal (<7) you know that the majority of the issues are coming from the L side of your heart, if there is a bigger discrepancy (i.e. >7) it may be two causes.

Transpulmonary gradient used to be used (mPAP - wedge>12 - may be pre-cap component to post-cap) but has been replaced by DPG.

• Group 1 PAH: Most important pre-capillary

• Group 2 (2/2 Left Heart): Post-capillary most of time

• Group 3 (2/2 lung disease): Predominantly pre-capillary

• Group 4: (CTEPH): Predominantly pre-capillary

• Group 5: a mess, can be anything

 Initiation and Titration of pulmonary vasoldilators

Pulmonary vasodilators are used in the treatment of treatment of pulmonary hypertension.

• Flolan (Epoprostenol) - the first drug approved by FDA; specifically pulmonary arterial hypertension, as well as pHTN related to scleroderma, lupus, congeital heart disease, diet-pill associated and stimulant associated pHTN

  • Delviered by continuous infusion

  • Mixed on a daily basis and refridgerated

• Veletri (Epoprostenol) - used in PAH as well as pHTN related to scleroderma, lupus, congeital heart disease. It is for patients with severe disease that have not responded to conventional therapy.

  • Delivered by continuous infusion via an ambulatory infusion pump

  • Requires less frequent mixing and does not have to be continuously refriderated

• Remodulin (Treprostinil) - structulrally related to Flolan; approved for PAH, pulmonay hypertension 2/2 connective tissue dsiease. Some experience of this drug in congenital heart disease. Studies have shown it increases exercise tolerance and decreased PA pressure

  • Delivered via continuous infusion either intravenous or subcutaneous through a CAD pump

  • Does not need to be mixed or refridgerated, although pain at infusion site for the subcutaneous route is a significant problem for many patients

  • Perioidic monitoring of blood counts is required

• Iloprost (Ventavis) - approved for use in pateitns with WHO group I pHTN (idiopathic PAH, familial PAH, assocaited PAH)

  • Inhaled via nebulizer; recommended use 6-9 times daily

  • Usu less flushing and diarrhea

https://med.stanford.edu/wallcenter/patient_care/patient-resources/fda.html

Sources:

https://depts.washington.edu/pulmcc/conferences/coreconfpdfs/04.21.2016%20--%20Pulmonary%20Hypertension%20--%20Laura%20Hooper%20MD.pdf