12. Pulmonary Hypertension (PH)

Definition

  • Mean pulmonary artery pressure (PAP) ≥20mmHg and pulmonary vascular resistance (PVR) >3 Woods unit (WU).
  • Mean PAP = 1/3 (systolic PAP – diastolic PAP) + diastolic PAP; normal mean PAP is ~14mmHg.
  • Mean PAP at right heart catheterization roughly correlates to systolic PAP estimated by echo Doppler.

Group I defined as above and pulmonary arterial wedge pressure ≤15mmHg.

Classification 

Pulmonary hypertension can be the end result of many different causes and classification enables appropriate treatment.  Mechanistic classification and common etiologies are described in the table below:

WHO Group

Etiology
  1. Pulmonary arterial hypertension (PAH)

Subgroups

  1. PAH long-term responders to calcium channel blockers (CCB)
  2. PAH with overt features of venous/capillaries involvement (pulmonary veno-occlusive disease & pulmonary capillary hemangiomatosis)

Idiopathic, heritable, drug and toxin (meth, dasatinib), connective tissue disease, HIV infection, portal hypertension, congenital heart disease (e.g., VSD, ASD), schistosomiasis
  1. PH due to left heart disease

HFrEF, HFpEF, valvular disease
  1. PH due to lung diseases and/or hypoxemia

COPD, interstitial lung disease, other pulmonary diseases with mixed restrictive and obstructive pattern, sleep–disordered breathing, alveolar hypoventilation, chronic exposure to high-altitude and developmental abnormalities
  1. Chronic thromboembolic pulmonary hypertension (CTEPH)

Obstruction of the pulmonary arteries due to pulmonary emboli or other pulmonary artery obstructions
  1. PH with unclear multifactorial mechanisms
  • Hematologic disorders: myeloproliferative disorders, chronic hemolytic anemia, splenectomy
  • Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis
  • Metabolic disorders: glycogen storage, Gaucher, thyroid
  • Other: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis

Updated WHO classification, Dana Point 2009

Evaluation, Diagnosis and Further Workup

  • History: SOB, DOE, fatigue, syncope, CP, signs of right-sided HF, diet pills (fenfluramine in Fen-phen), high-risk groups (HIV, meth use, scleroderma, OSA, etc.). 
  • Exam: elevated JVP, RV heave, loud P2, tricuspid regurgitation, signs of RV failure.
  • Labs: CBC with diff, platelet count, liver panel, thyroid function tests, HIV, hepatitis, screening for connective tissue disease (ESR, ANA, RF, anti-Scl 70 antibodies), BNP for prognosis.
  • ECG: RAD, RVH (R/S >1 in V1), p-pulmonale, incomplete or complete RBBB.
  • CXR: enlarged central PAs, “pruning” of distal PAs, RV enlargement (filling in of retrosternal space on lateral).
  • TTE with bubble study: most useful non-invasive screening tool to assess estimated PA systolic pressure (~>40mmHg), evaluate RV size and function, identify structural heart disease or cardiac shunt.
  • PFTs and ABGs: to evaluate for intrinsic lung disease; including TLC, DLCO.
  • Overnight oximetry: nocturnal desaturation +/- polysomnography to r/o sleep-disordered breathing.
  • Six-minute walk test: correlates with survival, establishes a baseline, and used longitudinally to assess response to therapy.

Second pass evaluation as appropriate:

  • Right heart cardiac catheterization: gold standard and needed to confirm diagnosis, r/o left heart disease, and guide therapy with vasodilator testing (indicated for Group I, responders have a reduction of 10mmHg in mean PAP to an absolute of <40mmHg and no decrease in CO to the appropriate vasodilator – likely iNO).
  • V/Q scan: to evaluate for chronic thromboembolic PH; low probability V/Q scan excludes CTEPH. Patients with idiopathic PAH may have “mottled appearance” on V/Q scan from thrombosis in situ. Do not substitute V/Q scan with contrast CT as the latter may miss CTEPH.
  • High-resolution CT chest: to evaluate for interstitial lung disease if suggested by PFTs.
  • Cardiopulmonary exercise testing.

​Treatment

WHO Group

Treatment

I

Mainstay:

Vasodilator responders: CCB (nifedipine, diltiazem ER, or amlodipine) in IPAH, HPAH, DPAH

Vasodilator non-responders – generally use combination therapy except in specific patient subsets

  • Prostanoids: epoprostenol IV (shown to prolong survival), treprostinil SC/IV/inhaled, iloprost inhaled, selexipag PO
  • Endothelin receptor antagonist (improve exercise tolerance): bosentan, ambrisentan, macitentan PO
  • PDE-5 inhibitors: sildenafil PO/IV, and tadalafil PO
  • Soluble guanylate cyclase stimulator: riociguat

Also consider lung transplantation, balloon atrial septostomy

Supportive:

  • Oxygen supplementation to help limit vasoconstriction (SaO2>90%), class I
  • Diuretics to manage RV overload, class I
  • Birth control (high mortality associated with delivery), class I
  • Consider oral anticoagulation in IPAH, HPAH, DPAH, class IIb
  • Consider anemia/iron correction, class IIb

II

Optimize management of heart failure or valvular abnormality. Studies have failed to demonstrate benefit from epoprostenol (FIRST – stopped due to increased mortality), bosentan (REACH1 trial – stopped due to safety issues), or PDE-5 inhibitors in patients with HFrEF and PH

III

Treat the underlying lung disorder, including oxygen if appropriate. PAH-specific therapy is NOT generally recommended

IV

Lifelong anticoagulation unless contraindicated. Pulmonary endarterectomy remains a curative option. Limited data exists but some PAH-specific treatments appear promising

V

Limited data, in general treat underlying disorder

CCB: calcium-channel blocker; PAH: pulmonary arterial hypertension; IPAH: idiopathic PAH; HPAH: heritable PHA; DPAH: drug-induced PAH; PDE-5: phosphodiesterase type 5

Management of Acute Decompensated Right Heart Failure in PH

PH group should be involved. Principles of management: 1) identify and treat underlying precipitating factors, 2) optimize fluid balance, 3) reduce RV afterload, 4) restore/maintain organ perfusion.

  • Treat precipitating factors: infection, anemia, thyroid disorders, dysrhythmias, ischemia, PE, dietary indiscretion, NSAIDs, COX-2 inhibitors. Dysrhythmias typically include atrial tachyarrhythmias but increased risk for ventricular arrhythmias or SCD. Attempts should be made to maintain sinus rhythm as much as possible.
  • Reduce excessive RV preload/volume overload: decompression of the RV will improve LV filling; relieve organ congestion.
  • Diuretics: intermittent or continuous infusion loop diuretics (initial bolus furosemide 20-40mg, followed by drip of 5-20mg/hr; initial bumex bolus of 1-4mg followed by drip of 0.5-0.8mg/hr; torsemide can also be used), +/- thiazide, +/- aldosterone antagonists.
  • Mechanical volume removal: CVVH/aquapheresis.
  • Avoid volume loading in patients presenting with hypotension or pre-renal azotemia in face of elevated JVP. No benefit from RV Frank-Starling mechanism (with failing RV, cardiac output will not increase with increase in preload); fluid loading further dilates RV and reduces LV filling thereby adversely affecting systemic cardiac output.
  • Reduce RV afterload (reduce pulmonary vascular resistance): oxygen, iNO, other inhalational agents; IV epoprostenol; combination therapy. Intubation in RV failure can lead to hemodynamic collapse and should be avoided if possible.
  • Augment RV contractility. Low dose dobutamine/dopamine 1-2mcg/kg/min can augment CO and reduce PVR; consider addition of other adrenergic agents (e.g., epi, norepi) which can augment CO and SVR more than PVR. Low dose vasopressin can be used in patients with vasodilatory shock and PH.

Caring Wisely Pearls

  • Patients with PH should be referred to a PH center for evaluation for advanced therapies.
  • The REVEAL PAH risk score estimates one-year survival in patients with newly diagnosed Group 1 PAH. In general, the prognosis of untreated PAH is poor, depends on the underlying etiology, and survival is worse compared to patients in other WHO groups.

 

Badesch DB, Champion HC, Gomez-Sanchez MA, et al. Diagnosis and assessment of pulmonary arterial hypertension. JACC. 2009; 54: Suppl., S55–S66.

Haddad F, Doyle R, Murphy DJ et al. Right ventricular failure in cardiovascular disease part II : pathophysiology, clinical importance, and management of right ventricular failure. Circulation. 2008 Apr 1;117(13):1717-31

McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension. Circulation. 2009;119: 2250-2294.

Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 2019; 53.

Tonelli AR. “This Patient May Have Pulmonary Hypertension. Now What?” ACC.org, 31Jan 2020, <https://www.acc.org/latest-in-cardiology/articles/2020/01/31/08/00/this-patient-may-have-pulmonary-hypertension>