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pulmonary hypertension

Chronic disorder with mean pulmonary artery pressure of > 20-25 mm Hg at rest or > 30 mm Hg with exercise & a pulmonary capillary wedge pressure < 15 mm Hg measured during right heart catheterization.* * see Differential diagnosis: below for causes of acute elevation in pulmonary artery pressure. Etiology: 1) left atrial hypertension* a) valvular heart disease - mitral stenosis b) heart failure - LV systolic dysfunction - LV diastolic dysfunction (most common in elderly, USA) [13] (28%) - left ventricular end-diastolic pressure (LVEDP) > 15 mm Hg [11] - congenital heart disease 2) hypoxemia* a) chronic lung disease - COPD - interstitial lung disease - pulmonary fibrosis - chronic pulmonary embolism b) severe nocturnal hypoxemia (sleep apnea) c) high altitude, chronic mountain sickness d) obesity hypoventilation syndrome 3) left to right shunts - atrial septal defect 4) vascular diseases of the lung - chronic thromboembolism - chronic thromboembolic pulmonary hypertension 5) connective tissue disease - systemic lupus erythematosus - systemic sclerosis 6) HIV1 infection 7) portal hypertension, portopulmonary hypertension 8) schistosomiasis (world-wide most common cause) 9) chronic hemolytic anemia - sickle cell disease (older patients) [8,15] 10) familial, congenital heart disease (see Genetics below) - persistent pulmonary hypertension of the newborn 11) pharmaceutical agents: analeptics 12) toxin exposure 13) idiopathic (primary pulmonary hypertension, group 1) (14%) [13] * left heart disease & hypoxemia due to chronic lung disease most common causes [3] * see causes of pulmonary hypertension for more detail Pathology: 1) vascular a) elevated mean pulmonary artery pressure due to increased pulmonary vascular resistance b) arterial intimal proliferation & arteriolar constriction secondary to alveolar hypoxia - disease localized to small pulmonary arterioles resulting in high pulmonary vascular resistance is primary pulmonary arterial hypertension c) increased pulmonary blood flow from left to right shunts d) increased pulmonary venous pressure from left heart failure* e) > 50% of the vascular bed must be occluded to produce clinical pulmonary hypertension 2) perivascular parenchymal changes resisting blood flow a) pulmonary fibrosis b) pulmonary edema 3) intravascular obstruction a) thromboembolism b) parasitic disease (schistosomiasis) 4) cor pulmonale may result from right ventricular overload * increased mean pulmonary artery pressure with elevated pulmonary artery capillary wedge pressure indicates pulmonary venous hypertension Genetics: - ALK1 mutation - endoglin mutation - BMPR2 mutation [12] Clinical manifestations: (also see primary pulmonary hypertension) 1) exertional dyspnea 2) fatigue 3) syncope 4) peripheral edema 5) persistent unexplained hoarseness 6) right ventricular heave 7) loud pulmonic valve component of the 2nd heart sound P2 - widely split S2 8) systolic murmur best heard at the left sternal border that increases with inspiration 9) diastolic murmur of tricuspid regurgitation 10) right-sided S3 gallop or S4 gallop heart sound - S3 gallop best heard at the left sternal border with the patient supine - listen during inspiration, murmur increases with inspiration 11) jugular venous distension with a large a wave 12) lungs are clear to auscultation 13) chest pain 14) Raynaud phenomenon suggesting connective tissue disease (see etiology) Laboratory: 1) antinuclear antibody (ANA) 2) HIV testing 3) serum pro-BNP improves predictive value in patients with sickle cell disease [8] 4) serum ALT, serum AST 5) arterial blood gas (hypoxemia, hypercapnia) Special laboratory: 1) echocardiography (initial diagnostic test of choice) [3] a) elevated pulmonary artery pressure 1] mean pulmonary artery pressure > 25 mm Hg at rest [3] 2] normal range: 15-30/5-13 (mean 10-18) mm Hg 3] echocardiography may underestimate true pulmonary artery pressure 4] right ventricular hypertrophy, right ventricular dilation, right ventricular failure b) rule out mitral stenosis c) bubble-contrast or transesophageal echocardiogram for congenital heart disease 2) electrocardiogram: (EKG) a) right ventricular hypertrophy b) RVH by EKG found in only 1/3 of patients with COPD & cor pulmonale c) RBBB often occurs d) right axis deviation e) T wave changes [9] 3) pulmonary function testing - isolated decrease in DLCO with normal TLC, FEV & FEV1 - SaO2 during sleep (overnight pulse oximetry) & with exertion 6-minute walk may determine need for oxygen therapy [3] - 6-minute walk improves predictive value in patients with sickle cell disease [8] 4) polysomnography - if suspected sleep disordered breathing [3] - rule out severe nocturnal hypoxemia - overnight pulse oximetry may suffice [3] 5) pulmonary artery catheterization with vasodilator test a) indications - suspected pulmonary artery hypertension suggested by clinical presentation not confirmed by echocardiography [3] - allows measurement of mean pulmonary artery pressure > 20 mm Hg (diagnostic) - most patients with confirmed pulmonary hypertension [3] - not indicated in pulmonary hypertension due to heart failure [3] - patients with connective tissue disease or other disorder associated with pulmonary parenchymal disease [3] b) IV vasodilator (adenosine, epoprostenol) c) inhaled nitric oxide d) vasoreactivity verified by 1] reduction in mean pulmonary artery pressure of at least 10 mm of Hg to a value <= 40 mm Hg 2] no decrease in cardiac output with vasodilation [3] 6) acute vasoreactivity study - assess response to vasodilator(s) 7) left heart catheterization & coronary angiography to exclude LV dysfunction [3] 8) open lung biopsy may be indicated Radiology: 1) chest radiograph a) enlarged right ventricle b) dilated pulmonary arteries [9] c) reduced peripheral pulmonary vascularity [3] 2) CT angiography if acute pulmonary embolism suspected 3) ventilation perfusion scan (V/Q scan) prior to pulmonary angiography in patients with - suspected pulmonary embolism [3] - suspected chronic thromboembolic pulmonary hypertension 4) pulmonary angiography may be appropriate if VQ scan is equivoval 5) findings on chest CT can identify patients with pulmonary hypertension due to left heart failure [24] Differential diagnosis: - acute onset pulmonary hypertension due to pulmonary embolism - non-collapsing inferior vena cava - right ventricular dilation with septal bowing & preserved ejection fraction Complications: 1) hypoxia 2) cor pulmonale 3) even borderline pulmonary hypertension associated with 31% increased risk of all-cause mortality [23] 4) complications associated with elective non-cardiac surgery include myocardial ischemia, venous thromboembolism, cardiogenic shock, & dysrhythmias [3] * mean pulmonary artery pressure of 19-24 mm Hg Management: 1) treat underlying cause - steroids for connective tissue disease, COPD - treatment of left heart failure with vasodilator may overload left ventricle worsening congestive heart failure [3] - treatment of lung disease with vasodilator may worsen VQ mismatch [3] - see [17] for guidelines treating pulmonary hypertension in children 2) supplemental oxygen in patients that are hypoxemic - 6 minute walk & overnight pulse oximetry may qualify patients for oxygen therapy (SaO2 < 88%) 3) anticoagulation with warfarin unless contraindicated [3] - this recommendation in the absence of thromboembolism not well understood 4) calcium channel antagonists a) invasive hemodynamic monitoring required prior to initiating therapy to verify vasoreactivity (see primary pulmonary hypertension) b) effective in some patients with primary pulmonary hypertension (pulmonary Raynaud's phenomenon) c) adverse effect of possibly worsening gas exchange d) nifedipine 120-240 mg QD e) diltiazem 540-900 mg QD 5) phosphodiesterase-5 inhibitors - sildenafil - sildenafil improves exercise capacity, WHO functional class, & hemodynamics [5] in patients with mild pulmonary hypertension - recommended adult dose of 20 mg TID [30] - 5 mg TID non-inferior to 80 mg TID [30] - tadalafil [3] - riociguat in place of PDE-5 inhibitor may be of benefit - useful for patients with negative vasoreactivity testing - does not facilitate elective surgery in high-risk patients [3] 6) endothelin receptor antagonists - bosentan - ambrisentan - macitentan (Opsumit) - macitentan/tadalafil (Opsynvi) improves exercise capacity - useful for patients with negative vasoreactivity testing 7) prostacyclin analogues - treprostinil intravenous - epoprostenol intravenous - inhaled iloprost - reserved for patients whose disease has progressed despite oral therapy with phosphodiesterase-5 inhibitor or endothelin receptor antagonist [3] - only prostacyclin analogues reduce mortality [31] 8) triple therapy of PDE-5 inhibitor, endothelin receptor antagonist & prostacyclin analogue may be better than monotherapy 9) other treatment options - sotatercept (Winrevair) improves exercise capacity FDA-approved March 2024 - industry-sponsored study suggests benefit for initial therapy with ambrisentan (Letairis) 10 mg + tadalafil (Adcirca) 40 mg) PO QD [16] - nitrates may have short-term benefit - treatment with vascodilator not curative but improves survival [3] - diuretics - consider digoxin [3] 10) chronic pulmonary embolism a) anticoagulation if pulmonary embolism suspected b) surgical thromboendarterectomy if indicated in patients with pulmonary embolism c) chronic anticoagulation d) inferior vena cava interruption (Greenfield filter) 11) consider exercise training [3] 12) delay or cancel elective surgery for patients with high risk pulmonary hypertension [3] 13) patients with severe pulmonary hypertension or right ventricular dysfunction should be referred to pulmonary hypertension center [3] 14) lung or heart/lung transplantation 15) advise against pregnancy if severe; maternal mortality 30-50% 16) screen for portal hypertension prior to liver transplantation 17) screening: a) 1st degree relatives of patients with familial pulmonary hypertension b) congenital heart disease with systemic-to-pulmonary shunt

Interactions

disease interactions

Related

causes of pulmonary hypertension pulmonary artery pressure (PAP) right ventricular failure; right heart failure right ventricular hypertrophy (RVH)

Specific

chronic thromboembolic pulmonary hypertension (CTEPH) portopulmonary hypertension primary pulmonary hypertension (PPH) pulmonary venous hypertension

General

arterial disease cardiopulmonary disease sign/symptom

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 256
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  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - McGlothlin DP, Granton J, Klepetko W, et al. ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery [Editorial]. J Heart Lung Transplant. 2022;41:1135-1194. PMID: 36123001
  4. Smith R., Jewish Home for the Aging, Reseda CA, 2001, unpublished
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  9. Geriatrics at your Fingertips, 13th edition, 2011 Reuben DB et al (eds) American Geriatric Society
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