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], Rim Halaby, M.D. [3]

Overview

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

Click here for the complete list of causes.

Management

Diagnosis

A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.

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

Inquire about past medical history ❑ Cardiovascular disease ❑ Congenital heart disease ❑ Left ventricular failure ❑ Pulmonary disease ❑ Previous PE ❑ COPD ❑ Interstitial lung disease ❑ Sleep apnea ❑ Asthma ❑ Recent surgery (<3 months) (suggestive of PE) ❑ Conective tissue disease ❑ HIV infection ❑ Portal hypertension ❑ Chronic hemolytic anemia ❑ Myeloproliferative disorders ❑ Splenectomy ❑ Systemic diseases ❑ Sarcoidosis ❑ Pulmonary Langerhans histiocytosis ❑ Lung tumors ❑ Chronic kidney disease in dialysis ❑ Thyroid disorders

Inquire about risk factors ❑ Family history of pulmonary hypertension ❑ Drugs ❑ Anorectic drugs ❑ Amphetamines ❑ Cocaine ❑ Phenylpropanolamine ❑ Saint John's wort ❑ Chemotherapeutic agents ❑ Selective serotonin reuptake inhibitors

Examine the patient: Vitals ❑ Pulse ❑ Tachycardia may be present ❑ Respiratory rate ❑ Tachypnea indicates more advanced disease 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 ❑ Hypotension 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, excessive 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

Order tests: ❑ Chest X-ray ❑ Pulmonary artery dilation ❑ Loss of periferal blood vessels ❑ Enlargement of the right chambers ❑ Pulmonary diseases ❑ Left heart abnormalities ❑ EKG ❑ Signs of right ventricle hypertrophy ❑ Right axis deviation ❑ Supraventricular arrhythmias such as atrial flutter and AF (suggestive of severe disease) ❑ Echocardiogram ❑ Pulmonary artery pressure ❑ Valvular disease such as MR, MS, AS ❑ Left ventricle systolic or dyastolic dysfunction ❑ Thrombus in right chambers (suggestive of pulmonary embolism) ❑ Pulmonary stenosis ❑ Right heart catherization

Findings suggestive of heart disease or pulmonary disease

Yes

No

Heart disease

Pulmonary disease

Perform V/Q test

Perfusion defects

Normal V/Q test

Chronic thromboembolism

Perform right heart catheterization ❑ Mean pulmonary arterial pressure ≥ 25 mmHg ❑ Pulmonary wedge pressure ≤ 15 mmHg

Yes

No

Pulmonary artery hypertension

Consider other causes ❑ Conective tissue disease ❑ HIV infection ❑ Portal hypertension ❑ Chronic hemolytic anemia ❑ Myeloproliferative disorders ❑ Splenectomy ❑ Sarcoidosis ❑ Chronic kidney disease in dialysis ❑ Thyroid disorders

Treatment

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

Acute vasoreactivity testing ❑ Epoprostenol IV 2ng/Kg/min every 10 to 15 min, OR ❑ Adenosine IV 50 mcg/Kg/min every 2 min, OR ❑ Nitric oxide (inhaled)

Positive

Negative

Oral calcium channel blocker (CCB)

Lower risk

Higher risk

❑ Follow closely for efficacy and safety ❑ Sustained response?

❑ Oral endothelin receptor antagonists: Bostenan 125 mg BD, OR Oral phospodiesterase-5 inhibitors: Sildenafil 20 mg TDS ❑ IV epoprostenol (started at 2 ng/Kg/min - 25-40 ng/kg/min), OR IV treprostinil (83 ng/Kg/min) ❑ Iloprost (inhaled) ❑ Treprostinil (SC)

❑ IV epoprostenol (started at 2 ng/Kg/min - 25-40 ng/kg/min), OR IV treprostinil (83 ng/Kg/min) ❑ Iloprost (inhaled) ❑ Oral endothelin receptor antagonists: Bostenan 125 mg BD, OR Oral phospodiesterase-5 inhibitors: Sildenafil 20 mg TDS ❑ Treprostinil (SC)

Yes

❑ Reassess

Response to the monotherapy ❑ No evidence of heart failure on physical exam ❑ Functional class I/II ❑ 6 minute walk distance >400 m ❑ Normal RV size on echocardiogram ❑ Normal right atrial pressure and cardiac index ❑ Near normal or stable BNP

Unstable clinical course ❑ Signs of heart failure ❑ Functional class IV ❑ 6 minute walk distance <400 m ❑ RV enlargement on echocardiogram ❑ High right atrial pressure and low cardiac index ❑ Elevated/increasing BNP

Continue CCB

❑ Consider combo-therapy

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

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

Follow Up Testing

Shown below is a table depicting the follow up testing after etiology for pulmonary hypertension is established.

Condition	Follow up testing
BMPR2 mutation	❑ Yearly echocardiogram ❑ Right heart catheterization if evidence of PH
1st degree relative of patient with BMPR2 mutation or with 2 or more relatives with PH	❑ Genetic counseling for BMPR2 testing ❑ Proceed as above if 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 echocardiography
Portal hypertension	❑ If considering liver transplant perform echocardiogram ❑ Right heart catheterization if evidence of PH
CHD with shunt	❑ Echocardiogram and right heart catheterization at the time of diagnosis ❑ Repair any significant defect
Recent acute pulmonary embolism	❑ If symptomatic 3 months after event, perform ventilation perfusion scintigraphy ❑ Do a pulmonary angiogram if positive
Prior fenfluramine use (appetite suppressant)	❑ Echocardiogram only if symptomatic
Sickle cell disease	❑ Yearly echocardiogram ❑ Right heart catheterization if evidence of PH

Do's

• Monitor liver function tests monthly in patients being treated with endothelin receptor antagonists.
• Follow up on patients with advanced symptoms, right heart failure, advanced hemodynamics and those on parenteral or combination therapy every 3 months.

Don'ts

• Do not perform vasospastic testing for those with overt heart failure or hemodynamic instability because calcium channel blocker will not be considered.