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 reflux 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 medusae → 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 antagonists (Bostenan 125 mg BD) (ERA's) or Phospodiesterase-5 inhibitors (PDE-5 Is) (Sildenafil - 20 mg TDS) (oral) ❑ Epoprostenol (started at 2 ng/Kg/min - 25-40 ng/kg/min) or Treprostinil (83 ng/Kg/min) (IV) ❑ Iloprost (inhaled) ❑ Treprostinil (SC)

❑ Epoprostenol (started at 2 ng/Kg/min - 25-40 ng/kg/min) or Treprostinil (83 ng/Kg/min) (IV) ❑ Iloprost (inhaled) ❑ ERAs (Bostenan 125 mg BD) or PDE-5 Is (Sildenafil - 20 mg TDS) ((Oral) ❑ Treprostinil (SC)

Yes

❑ Reassess

Clinical course Stable Physical examination No evidence of heart failure Functional class I/II 6MWD (Molecular weight distribution) (6 minute walk distance) 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 Functional class assessment Every clinic visit 6MWT (6 minute walk test) Every clinic visit Echocardiogram2 Q 12 months/center dependent BNP center dependent RHC (Right heart catheterization) Clinical deterioration and center dependent

Clinical course Unstable Physical examination Signs of heart failure Functional class IV 6MWD (Molecular weight distribution) (6 minute walk distance) 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 Functional class assessment Every clinic visit 6MWT (6 minute walk test) Every clinic visit Echocardiogram2 Q 6 to Q 12 months/center dependent BNP center dependent RHC (Right heart catheterization) 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.