History

The clinical manifestations of pulmonary arterial hypertension (PAH) are frequently masked by the underlying disease entities. Obtaining a careful history may help differentiate PAH from groups 2-5 pulmonary hypertension. Important clues to a specific cause include the following:

History of heart murmur
Deep venous thrombosis (DVT) or pulmonary embolism (PE)
Raynaud phenomenon
Arthritis or arthralgias
Rash
Heavy alcohol consumption
Hepatitis
Heavy snoring
Daytime hypersomnolence
Morning headaches
Morbid obesity
Family history of pulmonary hypertension
Drug use, in particularly diet drugs and illicit drugs
Medications

Patients with PAH may also have nonspecific symptoms secondary to pulmonary hypertension. These may include the following:

Dyspnea upon exertion
Fatigue
Lethargy
Syncope with exertion
Chest pain
Anorexia
Right upper quadrant pain

Less common symptoms include the following:

Cough
Hemoptysis
Hoarseness (due to compression of the recurrent laryngeal nerve by the distended pulmonary artery)

Physical Examination

The intensity of the pulmonic component of the second heart sound (P₂) may be increased and the P₂ may demonstrate fixed or paradoxic splitting. A systolic ejection murmur may be heard over the left sternal border. The murmur may be augmented by inspiration. A right ventricular heave may be palpated.

A prominent A wave may be observed in the jugular venous pulse. A right-sided fourth heart sound (S₄) with a left parasternal heave may be auscultated.

Right ventricular failure leads to systemic venous hypertension and cor pulmonale. The signs of right ventricular failure include a high-pitched systolic murmur of tricuspid regurgitation, hepatomegaly, a pulsatile liver, ascites, and peripheral edema. In this scenario, a right ventricular third heart (S₃) sound is also heard.

Signs of underlying cardiac, pulmonary, hepatic, or collagen-vascular disease are often present.

Patients with pulmonary arterial hypertension (PAH) often develop cor pulmonale, which further worsens hypoxemia and perpetuates pulmonary hypertension.

Complications

The most common—and feared—complication from pulmonary hypertension is right-sided heart failure. Progression to right-sided heart failure is part of the natural history of pulmonary arterial hypertension (PAH), and it is often present to some degree at the time of diagnosis. Registry and institutional data further implicate this as the most common cause of death in PAH patients, with data suggesting that 44-73% of PAH patients who die do so because of right-sided heart failure or sudden cardiac death.^{[18, 19]}

In addition to right-sided heart failure, other causes of death include complications that arise because of dilatation of the pulmonary artery. These include pulmonary artery dissection and rupture, massive hemoptysis, and left main compression syndrome, where the left main coronary artery is compressed by the pulmonary artery trunk.^[20]Hemoptysis is often secondary to a bronchial arterial source, as hypoxic vasoconstriction in the pulmonary arteries leads to collateralization and proliferation of the bronchial arteries. Supraventricular and, less commonly ventricular, arrhythmias may also occur, presumably triggered by right-sided heart disease.

Differential Diagnoses

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Media Gallery

Gross pathology on patient who died of severe pulmonary arterial hypertension secondary to persistent patent ductus arteriosus.
Close-up view of gross pathology on patient who died of severe arterial pulmonary hypertension secondary to persistent patent ductus arteriosus.
Chest radiograph of patient with nonidiopathic pulmonary hypertension shows enlarged pulmonary arteries. This patient had atrial septal defect.
54-year-old woman with history of scleroderma (CREST variety—ie, calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) developed dyspnea that worsened upon exertion. The patient was found to have severe pulmonary arterial hypertension.
54-year-old woman with history of scleroderma (CREST variety—ie, calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) developed dyspnea that worsened on exertion. Spiral CT showed enlarged pulmonary arteries but no evidence of thromboembolism.
Ventilation-perfusion scan of bilateral mismatched segmental and subsegmental defects, suggesting chronic thromboembolic hypertension.
A 34-year-old woman with history of scleroderma (CREST variety—ie, calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) developed dyspnea that worsened upon exertion. The patient was found to have severe pulmonary arterial hypertension.
A 34-year-old woman with history of scleroderma (CREST variety—ie, calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) developed dyspnea that worsened upon exertion. The patient was found to have severe pulmonary arterial hypertension.
A 34-year-old woman with history of scleroderma (CREST variety—ie, calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) developed dyspnea that worsened on exertion. A CT pulmonary angiogram showed a massively enlarged pulmonary artery.

of 9

Author

Kristin E Schwab, MD Fellow in Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Nader Kamangar, MD, FACP, FCCP, FCCM Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Medicine, Olive View-UCLA Medical Center

Nader Kamangar, MD, FACP, FCCP, FCCM is a member of the following medical societies: Academy of Persian Physicians, American Academy of Sleep Medicine, American Association for Bronchology and Interventional Pulmonology, American College of Chest Physicians, American College of Critical Care Medicine, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, Association of Pulmonary and Critical Care Medicine Program Directors, Association of Specialty Professors, California Sleep Society, California Thoracic Society, Clerkship Directors in Internal Medicine, Society of Critical Care Medicine, Trudeau Society of Los Angeles, World Association for Bronchology and Interventional Pulmonology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba Faculty of Medicine; Site Director, Respiratory Medicine, St Boniface General Hospital, Canada

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, World Medical Association

Disclosure: Nothing to disclose.

Kelvin Chan, MD Resident Physician, Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Olive View-UCLA Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

Oleh Wasyl Hnatiuk, MD Program Director, National Capital Consortium, Pulmonary and Critical Care, Walter Reed Army Medical Center; Associate Professor, Department of Medicine, Uniformed Services University of Health Sciences

Oleh Wasyl Hnatiuk, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Shahriar Pirouz, MD Resident Physician, Department of Internal Medicine, Olive View-UCLA Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment