Pulmonary hypertension overview
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Pulmonary hypertension (PH) is a condition of elevated blood pressure (>25 mmHg at rest) within the pulmonary artery of the lungs, leading to a myriad of symptoms including shortness of breath, dizziness, syncope, chest pain, tachycardia and leg swelling. PH has several differing etiologies and is a progressive and fatal disease if left untreated. PH is classified by the World Health Organization (WHO) into 5 different groups, which will be discussed later on this page. Treatment is generally targeted toward the underlying etiology of disease.
In 1891, a German physician Ernst von Romberg described pulmonary vascular sclerosis in an autopsy. In 1951 David Dresdale coined the term primary pulmonary hypertension for the first time. In 1951, David Dresdale coined the term primary pulmonary hypertension for the first time. In 1981, pulmonary hypertension registry landmark multi-center U.S. study characterizing natural history and clinical features of primary pulmonary hypertension (PPH).
Pulmonary hypertension (PH) has been previously classified as primary (currently known as idiopathic pulmonary arterial hypertension or IPAH) and secondary in 1973. In 1988, a clinical classification of PH into 5 groups has been developed during the 2nd World Symposium on PH in Evian, France. The clinical classification has been updated regularly as the understanding of PH expanded; nevertheless, the main scheme of classification into the 5 main groups remained intact. The classification of PH has been last modified in 2013 during the 5th World Symposium on Pulmonary Hypertension in Nice, France. The main 5 groups of PH include pulmonary arterial hypertension (Group 1), pulmonary hypertension due to left heart disease (Group 2), pulmonary hypertension due to chronic lung disease and/or hypoxia (Group 3), chronic thromboembolic pulmonary hypertension (Group 4), and pulmonary hypertension due to unclear multifactorial mechanisms (Group 5).
Pulmonary hypertension (PH) is a pathological condition of the pulmonary vasculature present in several disease states and leading to hemodynamical derangement. PH is defined as an elevated mean pulmonary artery pressure (PAP) as measured by right heart catheterization at rest. The factors that are in involved in the pathophysiology of the increase in the mean pulmonary arterial pressure are: increase in pulmonary vascular resistance, increase in the right sided cardiac output and increase in the mean pulmonary venous pressure. To note that “pulmonary arterial hypertension” (PAH) refers to group 1 PAH in the updated WHO classification. “pulmonary hypertension” (PH) refers to any of group 2 PH through group 5 PH. PH is also used when referring to all five groups collectively. Pulmonary arterial hypertension is characterized by endothelial dysfunction resulting from an imbalance between apoptosis and proliferation of pulmonary artery smooth muscle cells favoring the proliferation.
The World Health Organization (WHO) has classified PH based on etiology into five distinct groups -- Group 1 (pulmonary arterial hypertension), Group 2 (PH due to left heart failure), Group 3 (PH due to chronic lung disease and/or hypoxemia), Group 4 (PH due to chronic thromboembolic disease), and Group 5 (PH due to multifactorial mechanisms).
- Group 1 - Pulmonary arterial hypertension (PAH) - causes include idiopathic and heritable PAH (due to genetic defects), connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematosus, Raynaud Disease, and mixed connective tissue disease, HIV, drugs and toxins, and parasitic infections such as schistosomiasis
- Group 2 - Left Heart Disease - often characterized by chronically elevated left sided filling pressures as evidenced by left atrial dilation, possible mitral valve disease
- Group 3 - Lung disease and/or hypoxemia - causes include COPD, OSA
- Group 4 - Chronic Thromboembolic Disease
- Group 5 - PH due to multifactorial mechanisms, such as chronic hemolytic anemia, sarcoidosis, chronic kidney disease, and myeloproliferative disorders
Differentiating Pulmonary hypertension from Other Diseases
One of the most common initial presentations of patients with pulmonary hypertension is dyspnea; therefore, the differential diagnosis is very broad. As the disease progresses with time, more symptoms related to right ventricular hypertrophy and failure occur; which further narrows down the differential diagnosis.
Epidemiology and Demographics
Pulmonary arterial hypertension has been considered as a disease of young women. The mean age of patients in the U.S. registry was 36 years and the overall female-to-male ratio was 1.7:1.
Pulmonary hypertension (PH) is a multifactorial disease involving genetic and environmental risk factors. Risk factors for pulmonary arterial hypertension include BMPR2 mutation, connective tissue disease, HIV infection, portal hypertension, fenfluramine use, and congenital heart disease with shunt. Left heart and lung diseases are risk factors for PH. Patients with a hypercoagulable state (such as the presence of lupus anticoagulant, deficiency of protein C, protein S, or antithrombin III, chronic inflammatory disorders, myeloproliferative syndromes, and splenectomy) are at an increased risk for chronic thromboembolic pulmonary hypertension.
Patients with a known BMPR2 mutation, scleroderma, and portal hypertension undergoing evaluation for liver transplantation should receive periodic screening for pulmonary hypertension (PH) through a thorough assessment of the presence of symptoms, physical examination, chest X ray, electrocardiography, and echocardiogram. Additional investigation with right heart catheterization should be performed if screening is suggestive of the presence of PH.
Natural History, Complications and Prognosis
In the NHLBI registry for primary pulmonary hypertension, the mean interval from the onset of symptoms to diagnosis was 2 years, and the most common initial symptoms were dyspnea, fatigue, and syncope. There was an estimated median survival of 2.8 years for symptomatic patients who do not receive any treatment, with the most common cause of death as cor pulmonale.
Diagnostic Study of Choice
Pulmonary hypertension (PH) is a pathological condition of the pulmonary vasculature present in several disease states and leading to hemodynamical derangement. PH is defined as an elevated mean pulmonary artery pressure (PAP) as measured by right heart catheterization at rest.
History and Symptoms
When approaching a patient with suspected or confirmed pulmonary hypertension (PH), it is important to elicit a detailed clinical history. The presenting symptoms are important but a comprehensive past medical history, medication history, family history, social history, and review of systems may reveal further clues as to the etiology of the condition. The symptoms of PH include dyspnea, fatigue, and syncope.
Pulmonary hypertension (PH) can present with a myriad of physical signs that develop on a spectrum corresponding to the severity of the disease. PH is often initially associated with a loud P2, parasternal heave, and narrowed splitting of the second heart sound on physical examination. A third heart sound (S3) may also be heard on auscultation. As PH worsens, right ventricular failure can develop, which can be associated with as increased jugular venous pressure (JVP), ascites, peripheral edema, hepatojugular reflux, and clubbing. A pansystolic murmur of tricuspid insufficiency can also be present on physical examination and is suggestive long-standing PH.
Several laboratory tests are required in the evaluation of a patient for pulmonary hypertension. Laboratory tests help either in the exclusion of other differential diagnosis or in the determination of any medical condition that might be the cause of the pulmonary hypertension. Biochemistry, hematology and thyroid function tests are required in all patients with pulmonary hypertension.They are important for the diagnosis of chronic hemolytic anemia, myeloproliferative disorders, thyroid disorders and chronic renal failure on dialysis.
Elevated pulmonary pressures in pulmonary hypertension (PH) can lead to right ventricular hypertrophy (RVH) and right atrial enlargement which can sometimes be observed on electrocardiogram (ECG). The ECG findings of PH include right axis deviation, right ventricular strain pattern, and P pulmonale. The ECG findings of PH are neither specific nor sensitive and their absence does not rule out the presence of PH.
Chest X Ray
Chest X-ray is abnormal in the majority of patients with pulmonary hypertension (PH); however, there is no correlation between the severity of PH and the findings on chest X-ray. Findings of PH on chest X-ray include pulmonary artery dilatation and right sided enlargement of the heart. Chest X-ray allows the exclusion of left heart disease and lung disease that can lead to group 2 and group 3 PH, respectively.
CT scanning is a valuable, noninvasive procedure for confirming the presence of pulmonary hypertension. Different types of CT imaging have been used to rule out certain etiologies of pulmonary hypertension and to delineate the anatomy of the pulmonary vasculature.
Cardiac MRI provides important prognostic indicators regarding the function of right ventricle in patients with pulmonary hypertension.
Echocardiography or Ultrasound
Echocardiography may demonstrate enlargement of the right chambers with a thickened interventricular septum in patients with pulmonary hypertension. Right ventricular afterload may be suggested by a leftward septal displacement during systole. Pericardial effusions and diminished left ventricular cavity typically portend a dismal prognosis.
Right Heart Catheterization
Cardiac catheterization is still the gold standard for diagnosing, assessing the severity, and determining the prognosis and response to therapy in pulmonary hypertension. In the cardiac catheterization laboratory, inhaled nitric oxide is administered to determine if the pulmonary vasculature is still reactive or if the obstruction is fixed. It is dangerous to give nifedipine IV as a test because it could lead to a dangerous episode of hypotension. This procedure has been shown to be safe, with no deaths reported in the NIH registry study. In addition, a recent study reported a procedure-related mortality of 0.055%
Other diagnostic studies
Pulmonary hypertension is a diagnosis of exclusion; therefore, several diagnostic studies might be done to exclude other diseases or to determine any underlying medical condition causing pulmonary hypertension. These studies include pulmonary function tests, overnight oximetry, and ventilation-perfusion studies.
Prior to the initiation of therapy for pulmonary hypertension, a right heart catheterization should be performed to exclude (as a cause of the pulmonary hypertension. If type II pulmonary hypertension is confirmed than a vasodilator challenges performed to assess the reactivity of the pulmonary vasculature. If the pulmonary vasculature is reactive, then calcium channel blockers may be an appropriate therapy. If the pulmonary vasculature is not reactive than endothelin antagonist and processed annoyance are the optimal management. Patients with eisenmenger syndrome should not be administered calcium channel blockers. Pulmonary functions tests, imaging studies(V/P scan), and arterial oxygen saturation should also be obtained for every patient with PAH, in order to plan the therapy accordingly. If the patients fails to respond to medical therapy, surgery is considered.
The choice of treatment for pulmonary hypertension (PH) requires the assessment of the clinical severity of the disease and the identification of any underlying cause. Patients who have PH secondary to a medical condition such as left heart failure, lung diseases, or thromboembolic disease (PH group 2, 3, and 4 respectively) should receive treatment for the underlying cause. Patients who have pulmonary arterial hypertension (PAH) must undergo vasoreactivity testing in order to assist in the selection of the optimal therapy which includes calcium channel blockers, endothelin receptor antagonist, phosphodiesterase inhibitors, or prostanoids.
Patients with severe WHO functional class II or III pulmonary hypertension (PH) refractory to medical therapy are candidate for surgical intervention, such as atrial septostomy or lung transplantation. Pulmonary thromboendarterectomy (PTE) is a surgical procedure that is used for chronic thromboembolic pulmonary hypertension.
Genetic and environmental factors are involved in pulmonary hypertension (PH); therefore, not all cases of PH are preventable. PH that is secondary to other diseases such as left heart failure, chronic lung disease, chronic liver disease, and collagen vascular diseases among others can be prevented by the early and optimal treatment of these medical conditions. Patients who are at elevated risk for developing pulmonary arterial hypertension (PAH) must be monitored for the occurrence of symptoms of PAH. Patients at risk for PAH include subjects with systemic sclerosis or with genetic predisposition.
The recommended measures for the secondary prevention are avoiding pregnancy, rigorous follow up in case of pregnancy, avoid unnecessary surgeries, multidisciplinary care in case of necessary surgery, avoid high altitude, supplemental oxygen in order to ensure a target oxygen saturation of 91% in case of exposure to high altitude, up-to-date immunizations against influenza and pneumococcal pneumonia.