at: inbox

Pulmonology - Pulmonary Hypertension - Fast Facts | NEJM Resident 360

The pulmonary vasculature accommodates cardiac output at pressures less than one-quarter of the systemic circulation because it is a low-resistance, high-capacitance system. In pulmonary hypertension, various conditions lead to increased pulmonary arterial pressures, which result in right ventricular dysfunction. These patients develop symptoms of right-sided heart failure because the right ventricle, which is typically thin-walled, needs to exert against the increased pulmonary arterial pressure to maintain cardiac flow. Pulmonary arterial hypertension is defined by increased mean pulmonary arterial pressure (mPAP >20 mm Hg at rest).

A number of conditions can lead to pulmonary hypertension, including drug and toxin exposure, infections, congenital heart diseases, genetics, connective tissue disorders, and portal hypertension. The most common causes of pulmonary hypertension are left-sided heart failure and hypoxemic lung disease.

Assessment

Etiology: The World Health Organization (WHO) classifies pulmonary hypertension into five categories based on etiology and management of the condition. Therefore, differentiating the etiology of pulmonary hypertension is important to determining a management approach**.** Idiopathic pulmonary arterial hypertension (IPAH) is only diagnosed when the other conditions listed below are ruled out:

WHO Clinical Classification of Pulmonary Hypertension
1 Pulmonary arterial hypertension (PAH)
1.1 Idiopathic PAH
1.2 Heritable PAH
1.3 Drug- and toxin-induced PAH
1.4 PAH associated with:
1.4.1 Connective tissue disease
1.4.2 HIV infection
1.4.3 Portal hypertension
1.4.4 Congenital heart disease
1.4.5 Schistosomiasis
1.5 PAH long-term responders to calcium-channel blockers
1.6 PAH with overt features of venous/capillaries (PVOD/PCH) involvement
1.7 Persistent PH of the newborn syndrome
2 PH due to left-heart disease
2.1 PH due to heart failure with preserved LVEF
2.2 PH due to heart failure with reduced LVEF
2.3 Valvular heart disease
2.4 Congenital/acquired cardiovascular conditions leading to postcapillary PH
3 PH due to lung diseases and/or hypoxia
3.1 Obstructive lung disease
3.2 Restrictive lung disease
3.3 Other lung disease with mixed restrictive/obstructive pattern
3.4 Hypoxia without lung disease
3.5 Developmental lung disorders
4 PH due to pulmonary artery obstructions
4.1 Chronic thromboembolic PH
4.2 Other pulmonary artery obstructions
5 PH with unclear and/or multifactorial mechanisms
5.1 Hematological disorders
5.2 Systemic and metabolic disorders
5.3 Others
5.4 Complex congenital heart disease

Abbreviations: PH, pulmonary hypertension; PVOD/PCH, pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis; LVEF, left ventricular ejection fraction

(Reference: Haemodynamic Definitions and Updated Clinical Classification of Pulmonary Hypertension. Eur Respir J 2019.)

History: A careful history of symptoms and medical comorbidities can help guide the diagnosis. Early in the disease, patients are asymptomatic, but as the disease progresses, patients may experience exertional dyspnea, palpitations, chest pain, presyncope/syncope, and fatigue. Given the range of associated comorbidities, patients should be asked about history of chronic cardiac/lung disease or venous thromboembolism, symptoms of connective tissue disease, chronic lung infection, risk factors for HIV infection, and culprit medication use (e.g., fenfluramine, chemotherapy, interferon, or illicit drugs such as cocaine and methamphetamines).

Physical examination: Patients should be evaluated for evidence of right-sided heart failure. In early pulmonary hypertension, the patient may be relatively asymptomatic. The examination may be notable for the following:

• loud pulmonic valve (P2; the pulmonic valve component of the second heart sound heard over the left upper sternal border, which may become palpable as the disease progresses)

• holosystolic tricuspid regurgitation murmur

• elevated jugular venous pressure (with prominent A wave)

• right ventricular parasternal heave

• right-sided S3 or S4

• lower-extremity edema, ascites, and a pulsatile liver, which may be evident when there is significant tricuspid regurgitation

Investigations

Right-heart catheterization: Definitive diagnosis of pulmonary hypertension is made via right-heart catheterization and requires hemodynamic measurements of mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and the pulmonary capillary wedge pressure (PCWP). A diagnosis of idiopathic pulmonary arterial hypertension is supported by a resting mPAP >20 mm Hg with an elevated PVR ≥3 Wood units and a normal PCWP (e.g., ≤15 mm Hg).

Noninvasive tests: In addition to right-heart catheterization, some noninvasive tests may be indicated to determine the etiology of disease as listed in the WHO classification system above. In general, most patients suspected of having PH will receive a transthoracic echocardiogram as an initial screen for left ventricular function and an estimate of right-sided cardiac pressure. Other tests that should be considered in the evaluation of all patients for PH Include:

Investigative Tests and Pertinent Findings in the Evaluation of Pulmonary Hypertension

Diagnostic Test	Pertinent Findings
Blood work	Autoimmune serology (ANA, ENA, RF, ANCAs), transaminases, HIV serology, BNP
ECG	Evidence of right-axis deviation, right ventricular hypertrophy, and right atrial enlargement
Echocardiogram	RVSP can be used as a surrogate for the systolic pulmonary artery pressure Elevated RVSP levels are consistent with elevated pulmonary pressures (normal RVSP is <40 mm Hg) Abnormalities in right ventricular size and function will become apparent and should be monitored as disease progresses
Pulmonary function testing	Evidence of chronic lung disease can contribute to etiology Isolated reduction in diffusion capacity can be consistent with IPAH
Polysomnography	When clinical suspicion for sleep-disordered breathing and nocturnal hypoxemia is high
Arterial blood gas	Evidence of hypoxemia or chronic hypercapnia
6-minute walk	Evidence of exertional hypoxemia and decreased exercise tolerance
Ventilation–perfusion (VQ) scan	The most sensitive test to rule out chronic thromboembolic disease (e.g., for Group 4 PH)
High-resolution chest CT	To evaluate for lung disease including emphysema and interstitial lung diseases

Abbreviations: ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibody; BNP, brain natriuretic peptide; ECG, electrocardiogram; ENA, extractable nuclear antibodies; IPAH, idiopathic pulmonary arterial hypertension; PH, pulmonary hypertension; RF, rheumatoid factor; RVSP, right ventricular systolic pressure

Treatment

Therapy for PH is multifactorial, requiring management of the underlying etiology, treatment of the pathophysiology of disease (e.g., PH-specific therapy), and the consequent right-heart dysfunction.

PH group–specific therapy should first be optimized in all patients if possible. For example:

• In patients with Groups 2 and 3 disease, the underlying cardiac or pulmonary conditions should be optimized to prevent further progression of PH and symptoms of right-sided heart failure.

• Patients with Group 4 disease should receive anticoagulation and surgical consultation for possible thromboendarterectomy.

• In patients with more-advanced cardiac dysfunction, careful diuresis is needed to maintain euvolemia and supplemental oxygen is indicated to prevent chronic hypoxemia.

• Exercise training and routine vaccinations are recommended for all patients with pulmonary hypertension.

• Advanced therapy is reserved for patients with severe or progressive disease and requires specialist consultation. The therapeutic aim is for pulmonary vasodilation and targets three pathways:

1. Phosphodiesterase inhibitors such as sildenafil and tadalafil are phosphodiesterase type 5 inhibitors that exert a vasodilatory effect through the nitric oxide pathway.
2. Endothelin-receptor antagonists such as ambrisentan, bosentan, and macitentan exert their effects by counteracting endothelin-1, a vasoconstrictor and stimulator of smooth-muscle cells.
3. Prostacyclin agonists such as epoprostenol, treprostinil, and selexipag exert their effects by stimulating production of cyclic adenosine monophosphate (cAMP) and inducing endothelial relaxation.

• Calcium-channel blockers may be used in select patients with Group 1 PH who are deemed “vasoreactive” during testing at the time of right-heart catheterization.

Read more about evaluation and treatment of pulmonary hypertension here.

inbox