Pulmonary hypertension

Approach to patients with pulmonary hypertension

Talal Dahhan, MD, MSEd

 

Overview

  • Pulmonary hypertension (PH) is a common disease.  PH is generally classified into 5 groups by etiology / pathophysiology (although mixed disease–features of more than one group–can exist in a single patient):
    • elevation of LV filling pressures (Group II)
    • chronic lung disease-induced hypoxemia (Group III)
    • chronic venous thromboembolic disease (e.g., CTEPH; Group IV)
    • variety of other conditions that don’t fit well into the other groups (Group V; PCV, sarcoidosis, glycogen storage disease, etc).
    • Group I includes pulmonary arterial hypertension (PAH).  PAH is usually idiopathic, familial, genetic, connective tissue disease associated or HIV related
  • Therefore, a good way to think about all of these conditions is like this:
    • PH = secondary process (Groups II-V)
    • PAH = primary process driven by idiopathic, autoimmune, or drug-induced issues (Group I)
  • PAH is characterized by progressive remodeling of the distal pulmonary arteries, resulting in elevated pulmonary vascular resistance and, eventually, in right ventricular failure.
  • Over the past decade, knowledge of the basic pathobiology of PAH and its natural history, prognostic indicators, and therapeutic options have exploded.
  • A thorough evaluation of a patient is critical to correctly characterize the group where the PH patient falls in…and give the most appropriate management.
  • Aparna Swaminathan, MD (current senior Pulmonary and Critical Care fellow and a former Ambulatory Internal Medicine chief resident) presented a wonderful grand rounds on pulmonary hypertension. I think it is a nice review on the disease process and how we manage mixed disease patients. The following link goes to it (you need to log in using your NetID –Link: June 16th 2017 Medicine Grand Rounds)

 

Diagnosis

  • It remains a Right Heart Catheterization-based diagnosis (recent studies with new objective echocardiographic features could not get an accurate PCWP and PVR [Circulation J 2016 Aug 25;80(9):2019-25]):
    • mPAP > 25 mmHg is pulmonary hypertension; 25-30 —> mild, 30 – 35 —> moderate, and > 35 is severe (based on the older World Symosium of Pulmonary hypertension (WSPH) classification).
    • CO or Cardiac Index (CI) is the most important (< 2 L/min —> serious disease!).
    • PCWP (or PAOP) > 15 indicates high filling pressure or Pulmonary venous hypertension or Group II patients, while less than 12-15 is more in favor of Group I (after we rule out hypoxemia induced disease, and CTEPH).
    • Transpulmonary Gradient (TPG) = mean Pulmonary Artery Pressure – PAOP. Difference of more than 15 may indicate possible PAH on top of PH processes (mixed disease).
    • Diastolic Pulmonary Gradient = diastolic pulmonary pressure – PAOP or wedge pressure. Difference more than 5-7 mmHg may further prove PAH in these patients is more valuable [JACC Heart Fail. 2015 May;3(5):424-5].
    • A rise in PAOP after a 7 ml/Kg fluid bolus to above 15 mmHg gets a better chance to identify group II patients [CHEST 2017; 151(1):119-126]
    • Exercise RHC can unmask precapillary disease as well [Circ Heart Fail. 2010;3:588-595].
  • Cardiac studies, including: echocardiography and right heart catheterization, are key elements in the assessment of what group of a disease we have and how severe it is.
  • Given the multitude of treatment options currently available for PAH, assessment of risk and response to therapy is critical in long-term management.
  • One of the attached papers is a review article that underscores unique situations, including perioperative management, intensive care unit management, and pregnancy, and highlights the importance of collaborative care of the PAH patient through a multidisciplinary approach.

 

General measures and management options

  • Pulmonary rehabilitation: slow-paced respiration therapy is feasible in patients with PAH and may improve symptoms and lower IL-6. Therefore, patients need to be referred to pulmonary rehab [Heart Lung 2017 Jan – Feb;46(1):7-13].
  • Salt and fluid restriction, extrapolated for management of heart failure [Circulation. 2013;128(16):e240].
  • Diuretics: They diminish hepatic congestion, peripheral edema, and pleural effusions and may be of particular benefit in those in whom interventricular sepal deviation from elevated RV pressure impairs left ventricle output. Has clinical benefit to avoid end organ damage from PH [Eur Heart J. 2016;37(1):67].
  • Anticoagulation: might be favored in CCB responders’ Group I and Patients on maximum combination therapy Unless Connective Tissue Disease associated patients.
  • Avoid or Correct Anemia: can cause RV ischemia which leads to worsening disease.

 

Pharmacologic management

  • NO based pathway: iNO and PDE-V inhibitors (to inhibit metabolism): Sildenafil (Revatio), or Tadalafil (Adcirca) – (Side effects: headache, systemic hypotension, nasal fullness. Stop Tadalafil if eGFR < 45 ml/min or if septic with hypotension)
  • Endothelin Receptior Antagonists: Bosentan (Tracleer), Ambrisentan (Letairis) or Macitentan (Opsumit) – (Side effects: ankle edema, fluid retension and transaminitis (mainly with Bosentan)
  • Prostacyclin Analogues (Side effects: Jaw pain, nausea, headache, thrombocytopenia, diarrhea – More with parenteral than oral medications. Less with inhaled formulation):
    • Inhaled: Iloprost that we mostly use an inpatient now (Ventavis) or Treprostinil (Tyvaso) that is mostly as outpatient.
    • Oral: Treprostinil (Oreinitram) and Selexapag (Uptravi, prostacyclin agonist).
    • SC: Treprostinil (Remodulin).
    • IV: Epoprostenol (Lysine ‘Flolan’ or Arginine ‘Veletri) or Treprostinil (Remodulin) All must where accidental stopping or sudden discontinuation can cause cardiac arrest!
    • Soluble Guanylate Cyclase Stimulators (sGC stimulators) – Riociguat (Adempas): Only FDA approved medication in Group I and Group IV inoperable patients. Has PDE-V inhibitors side effects. Oral medication.

Eur Respir Rev 2014; 23: 469–475

 

Management of a Crashing Patient:  [ Em Med Clinics North Amer 2015 Aug;33(3):623-43 ]

  • Management goals for patients with pulmonary hypertension (PH) when acutely deteriorating, are:
    • To optimize preload and volume status – IVC assessment in non-intubated patients with CVP measurement seem to be to most reliable methods. JVP helps but can be misleading.
    • To maintain right ventricular function – monitoring end organ perfusion helps to assess stability, improvement or deterioration.
    • To prevent right coronary artery hypoperfusion.
    • To reduce right ventricular afterload – by decreasing PVR.
    • Reverse the underlying cause whenever possible – Sepsis, volume disturbances, concomitant cardiac illness (new onset of valvulopathy or LV issues) or worsening PH.
  • Right ventricular failure is a hallmark finding in patients with decompensated PH.
  • The bedside echocardiogram is the most useful tool when evaluating patients with PH and suspected right heart failure.  Check out this video of echocardiography in RV failure.
  • Atrial fibrillation, atrial flutter, and atrioventricular nodal reentrant tachycardia are the most common dysrhythmias in patients with PH. Rhythm control is preferred over rate control in patients with severe PH.
  • Large (more than 250 ml) intermittent and/or continuous fluid administration should be avoided in patients with PH because it often worsens pressure overload of the right heart.
  • If a patient presents hypotensive and not sure, consider early start of Dopamine (upto 10 mcg/kg/min), epinephrine or norepinephrine (upto 0.3 mcg/kg/min) until we verify volume status sure of the volume status.

 

Check this paper by McLaughlin (JACC 2015 May 12;65(18):1976-97).