Pulmonary hypertension resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: , Vidit Bhargava, M.B.B.S [2]

Definition

Pulmonary hypertension (PH) is defined by mean pulmonary artery pressure > 25, pulmonary capillary wedge pressure (PCWP), left atrial pressure, or left ventricular end diastolic pressure (LVEDP) ≤ 15 mm Hg; and a pulmonary vascular resistance (PVR) > than 3 Wood units.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Pulmonary embolism

Common Causes

• Congenital heart disease with left-to-right shunt (ASD, VSD, PDA)
• Congestive heart failure
• COPD
• Cor pulmonale
• Interstitial lung disease
• Obstructive sleep apnea
• Thromboembolism

Management

Characterize the symptoms: ❑ Progressive dyspnea ❑ Exertional dizziness and syncope ❑ Edema of the extremities ❑ Angina ❑ Palpitations

Examine the patient: Physical signs that reflect severity of PH ❑ Loud pulmonary second heart sound (P2) ❑ Systolic murmur suggestive of tricuspid regurgitation ❑ Raised jugular venous pressure (JVP) ❑ Early systolic click ❑ Left parasternal heave ❑ Right ventricular S4 Physical signs suggestive of moderate to severe PH ❑ Holosystolic murmur that increases with inspiration ❑ Increased jugular v waves ❑ Pulsatile liver ❑ Diastolic murmur ❑ Hepatojugular relux Physical signs suggestive of advanced PH with right ventricular failure ❑ Right ventricular S3 ❑ Distension of jugular veins ❑ Hepatomegaly ❑ Peripheral edema ❑ Ascites ❑ Low BP, cool extremities Physical signs suggestive of possible underlying causes ❑ Central cyanosis → Abnormal V/Q, shunt ❑ Clubbing → Congenital heart disease ❑ Cardiac auscultatory findings → Congenital or acquired heart disease ❑ Rales/decreased breath sounds/dullness → Pulmonary congestion ❑ Fine rales, acc. muscle use, wheezing, protracted respiration, cough → Pulmonary parenchymal disease ❑ Obesity, kyphoscoliosis, enlarged tonsils → Disordered ventilation ❑ Sclerodactyly, arthritis, telengiectasia, Raynaud phenomenon, rash → Connective tissue disorder ❑ Peripheral venous insufficiency →Possible venous thrombosis ❑ Venous stasis ulcers → Possible sickle cell disease ❑ Pulmonary vascular bruits → Chronic thromboembolic PH ❑ Splenomegaly, spider angiomata, palmar erythema, icterus, caput medusa → portal hypertension

Consider alternative diagnosis: ❑ Left sided heart failure ❑ Coronary artery disease ❑ Liver disease ❑ Budd-Chiari syndrome

❑ Anticoagulation +/- ❑ Diuretics +/- ❑ Oxygen therapy +/- ❑ Digoxin

Acute vasoreactivity testing Drug Route of administration Dose titration Dose range Side effects Epoprostenol Intravenous infusion 2ng/Kg/min every 10 to 15 min 2 to 10 ng/Kg/min headache, nausea, lightheadedness Adenosine Intravenous infusion 50 mcg/Kg/min every 2 min 50 to 250 mcg/Kg/min Dyspnea, chest pain, AV block Nitric oxide Inhaled None 10 to 80 ppm Increased left heart filling pressure

Positive

Negative

Oral calcium channel blocker (CCB)

Lower risk

Higher risk

❑ Follow closely for efficacy and safety ❑ Sustained response?

❑ Endothelin receptor antagonsists (ERA's) or Phospodiesterase-5 inhibitors (PDE-5 Is) (oral) ❑ Epoprostenol or Treprostinil (IV) ❑ Iloprost (inhaled) ❑ Treprostinil (SC)

❑ Epoprostenol or Treprostinil (IV) ❑ Iloprost (inhaled) ❑ ERAs or PDE-5 Is ((Oral) ❑ Treprostinil (SC)

Yes

❑ Reassess

Clinical course Stable Physical examination No evidence of heart failure Functional class I/II 6MWD Greater than 400 m Echocardiogram RV size normal Hemodynamics RAP normal CI normal BNP Near normal or stable Treatment Oral therapy Frequency of evaluation Q 3 to Q 6 months FC assessment Every clinic visit 6MWT Every clinic visit Echocardiogram2 Q 12 months/center dependent BNP center dependent RHC Clinical deterioration and center dependent

Clinical course Unstable Physical examination Signs of heart failure Functional class IV 6MWD Less than 400 m Echocardiogram RV Enlargement Hemodynamics RAP high CI low BNP Elevated/Increasing Treatment Intravenous prostacyclin and/or combination treatment Frequency of evaluation Q 1 to Q 3 months FC assessment Every clinic visit 6MWT Every clinic visit Echocardiogram2 Q 6 to Q 12 months/center dependent BNP center dependent RHC Q 6 to Q 12 months or clinical deterioration

Continue CCB

In case of absence of response to initial monotherapy: ❑ Consider combo-therapy

In case of progress despite optimal medical treatment: ❑ Investigational protocols, OR ❑ Atrial septostomy, OR ❑ Lung transplant

The following guideline is based on Expert consensus document on pulmonary hypertension published by ACCF/AHA in 2009.

Follow up testing after etiology for pulmonary hypertension is established:

Substrate	Futher action
BMPR2 mutation 1st degree relative of patient with BMPR2 mutation or with 2 or more relatives with PH	❑ Yearly echocardiogram, right heart catheterization if evidence of PH. ❑ Genetic counselling for BMPR2 testing, proceed as aboveif positive.
Systemic sclerosis	❑ Yearly echocardiogram, right heart catheterization if evidence of PH.
HIV infection	Do echocardiogram if signs & symptoms are suggestive of PH. Right heart catheterization if evidence of PH on echo.
Portal hypertension	❑ If considering orthotopic liver transplant perform echocardiogram. ❑ Right heart catheterization if evidence of PH.
CHD with shunt	❑ Echocardiogram and right heart catheterization at the time of diagnosis. ❑ If significant defect - repair.
Recent acute pulmonary embolism	❑ If symptomatic 3 months after event, perform ventilation perfusion scinitigraphy. ❑ Do a pulmonary angiogram if positive.
Prior appetite suppressant use (fenfluramine)	❑ Echocardiogram only if symptomatic.
Sickle cell disease	❑ Yearly echocardiogram, right heart catheterization if evidence of PH.

Do's

• The diagnosis of pulmonary hypertension requires confirmation with a right heart catheterization.
• Objective assessment of treatment measures includes:

• Exercise capacity.
• Hemodynamics.
• Survival.

• Epoprostenol is the only therapy that has been shown to prolong survival in patients with pulmonary hypertension.
• Monitor liver function tests monthly in patients being treated with endothelin receptor antagonists.
• Patients presenting with advanced symptoms, right heart failure, advanced hemodynamics and those on parenteral or combination therapy must be seen every 3 months.

Don'ts

• Do not perform vasospastic testing for those with overt heart failure or hemodynamic instability.