This Patient May Have Pulmonary Hypertension. Now What?

Pulmonary hypertension (PH) is a condition defined by an increase in the pulmonary pressures.1 There are different groups of PH that are based on the mechanisms of disease, clinical presentation, hemodynamic characteristics, and therapeutic response.1 Pulmonary arterial hypertension (PAH) is a type of PH characterized by narrowing of the pulmonary arteries that if left untreated leads to progressive right heart failure and death.2 Despite an increase in the recognition of the disease, there is still a delay in PAH diagnosis, with about 20% of patients identified after they experienced symptoms for more than 2 years.3 In other cases, the delay in recognition is even longer because PH symptoms are nonspecific and frequently attributed to other medical conditions.4,5

In clinical practice, it is common to encounter patients whose echocardiograms show elevated right ventricular (RV) pressure or who have confirmed PH and get admitted for worsening of their disease or an unrelated event. The echocardiogram is an essential tool because it helps estimate the probability of PH (i.e., low, intermediate, or high) based on peak tricuspid regurgitation velocity, the RV shape (RV/ left ventricle >1 and flattening of the interventricular septum), pulmonary artery (diameter >2.5 cm; RV outflow acceleration time <105 ms; early diastolic pulmonary regurgitation velocity >2.2 m/s) and inferior vena cava and right atrium (RA) size (inferior vena cava >2.1 cm with reduced inspiratory collapse; RA area >18 cm2). High probability of having PH is based on a peak tricuspid regurgitation velocity of >3.4 m/s or 2.9-3.4 m/s plus 2 or more findings from the aforementioned categories.6

In the presence of intermediate or high probability of PH, the next step is to consider left heart and lung diseases and obtain a ventilation/perfusion scan. Clinically significant left heart and lung diseases are the most common causes of PH and therefore need to be considered first.7 A ventilation/perfusion scan is recommended as an essential part of the initial work-up of the disease because chronic thromboembolic PH (CTEPH) is underrecognized and has different treatment opportunities (pulmonary thromboendarterectomy and balloon pulmonary angioplasty).8

Left heart disease is the predominant cause of PH in more than a third of the patients referred for evaluation.9 A correct differentiation between PH due to left heart disease and PAH is essential because treatments are strikingly different. In the first condition, PAH-specific therapies are not beneficial. In contrast, a vast number of therapies are currently approved for PAH by the US Food and Drug Administration. Recent proceedings in PH recommend assessing the pretest probability of left heart disease in patients with PH. A higher probability is directly associated with older age (>70 years), >2 cardiovascular risk factors (obesity, systemic hypertension, dyslipidemia and diabetes), previous cardiac interventions, current atrial fibrillation, structural heart disease, abnormal electrocardiogram (left bundle branch block or left ventricular hypertrophy), left atrial dilation, or >2 + mitral regurgitation on echocardiography.10

A right heart catheterization remains essential to better understand the foundation of the disease (i.e., pre-capillary, isolated post-capillary, and combined pre- and post-capillary PH)11 based on a pulmonary artery wedge pressure ≤15 or >15 mmHg and a pulmonary vascular resistance ≥3 or <3 Wood units.1 Pre-capillary PH is seen in patients with PAH and also in PH due to lung disease and/or hypoxia, CTEPH, and PH with unclear or multifactorial mechanisms; therefore, it is essential to exclude these conditions before considering PAH. PAH is subsequently divided in idiopathic, associated (connective tissue disease, congenital heart disease, portal hypertension, and HIV), drug- and toxin-induced, and heritable PAH.5 The PH classification was recently updated to include PAH with long-term response to calcium channel blockers and PAH with overt features of venous/capillaries involvement. It is not uncommon to have an overlap between different PH groups, which may explain why patients may have a suboptimal response to PAH-specific therapies.12-14

After the diagnosis of PAH is made, it is essential to assess the 1-year mortality risk because this evaluation impacts treatment decisions.15 Two methodologies are commonly used to assess risk: the French Pulmonary Hypertension Network (FPHN) and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0. The FPHN risk assessment totals the number of low-risk criteria (World Health Organization functional class I or II, 6-minute walk distance >440 m, RA pressure <8 mmHg, and cardiac index ≥2.5 L/min/m2).16 The REVEAL 2.0 risk score includes a larger number of variables but provides a greater risk discrimination than the FPHN.17

Treatment is based on the risk assessment; those with low or intermediate risk are usually given initial oral combination therapy (usually phosphodiestearase-5 inhibitors and endothelin receptor antagonists). Patients at high risk require initial combination therapy that includes parenteral prostacyclin analogues. Patients are followed at 3-6 months after treatment initiation to reassess risk. If patients continue to be at intermediate or high risk, then triple sequential combination therapy is indicated. If no improvement is evident, lung transplantation is considered.15

PAH patients can be hospitalized for PH-related or unrelated conditions. The REVEAL registry noted that 53% of the newly diagnosed PAH patients had 1 hospitalization during the first year after inclusion, and about half of the hospitalizations were PAH related.18 The PAH-related causes were predominantly congestive heart failure, placement or removal of a central venous catheter, escalation of PAH treatment, or catheter infection. Causes not directly related to PAH included infections, surgeries or procedures, hemorrhages, and gastrointestinal disorders. Not surprisingly, patients with PAH-related hospitalizations were sicker.18 Remarkably, the need for an intensive care admission is associated with poor prognosis, with a 1-year survival rate less than 50%.19 In these subjects, treatment of triggering factors, continuation or intensification of PAH therapies, optimization of preload/afterload/contractility/arterial blood pressure, and maintenance of sinus rhythm are essential components of the management.20,21

In summary, suspect PH in patients with unexplained dyspnea with or without signs of right heart failure, screen with echocardiography, and confirm diagnosis and identify hemodynamic type with right heart catheterization. It is essential to rule out CTEPH and PH related to left heart disease or lung disease/hypoxia because the management is different. Assess risk status and consider initiation of therapy based on this evaluation. If a PAH patient is hospitalized, continue PAH therapies, avoid large fluid shifts, and consult a PH specialist.

References

  1. Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 2019;53:1801913.
  2. Tonelli AR, Arelli V, Minai OA, et al. Causes and circumstances of death in pulmonary arterial hypertension. Am J Respir Crit Care Med 2013;188:365-9.
  3. Brown LM, Chen H, Halpern S, et al. Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry. Chest 2011;140:19-26.
  4. Strange G, Gabbay E, Kermeen F, et al. Time from symptoms to definitive diagnosis of idiopathic pulmonary arterial hypertension: The delay study. Pulm Circ 2013;3:89-94.
  5. Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest 2010;137:376-87.
  6. Frost A, Badesch D, Gibbs JSR, et al. Diagnosis of pulmonary hypertension. Eur Respir J 2019;53:1801904.
  7. Strange G, Playford D, Stewart S, et al. Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort. Heart 2012;98:1805-11.
  8. Kim NH, Delcroix M, Jais X, et al. Chronic thromboembolic pulmonary hypertension. Eur Respir J 2019;53:1801915.
  9. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 2016;37:67-119.
  10. Vachiéry JL, Tedford RJ, Rosenkranz S, et al. Pulmonary hypertension due to left heart disease. Eur Respir J 2019;53:1801897.
  11. Guazzi M, Naeije R. Pulmonary Hypertension in Heart Failure: Pathophysiology, Pathobiology, and Emerging Clinical Perspectives. J Am Coll Cardiol 2017;69:1718-34.
  12. Opitz CF, Hoeper MM, Gibbs JS, et al. Pre-Capillary, Combined, and Post-Capillary Pulmonary Hypertension: A Pathophysiological Continuum. J Am Coll Cardiol 2016;68:368-78.
  13. McLaughlin VV, Vachiery JL, Oudiz RJ, et al. Patients with pulmonary arterial hypertension with and without cardiovascular risk factors: Results from the AMBITION trial. J Heart Lung Transplant 2019;38:1286-95.
  14. Bazan IS, Fares WH. Pulmonary hypertension: diagnostic and therapeutic challenges. Ther Clin Risk Manag 2015;11:1221-33.
  15. Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J 2019;53:1801889.
  16. Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J 2017;50:1700889.
  17. Benza RL, Gomberg-Maitland M, Elliott CG, et al. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. Chest 2019;156:323-37.
  18. Burger CD, Long PK, Shah MR, et al. Characterization of first-time hospitalizations in patients with newly diagnosed pulmonary arterial hypertension in the REVEAL registry. Chest 2014;146:1263-73.
  19. Tejwani V, Patel DC, Zein J, et al. Survival After an ICU Hospitalization for Pulmonary Hypertension. Chest 2018;154:229-31.
  20. Harjola VP, Mebazaa A, Čelutkienė J, et al. Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology. Eur J Heart Fail 2016;18:226-41.
  21. Hoeper MM, Benza RL, Corris P, et al. Intensive care, right ventricular support and lung transplantation in patients with pulmonary hypertension. Eur Respir J 2019;53:1801906.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Valvular Heart Disease, Lipid Metabolism, Acute Heart Failure, Pulmonary Hypertension, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound, Hypertension

Keywords: Hypertension, Hypertension, Pulmonary, Pulmonary Artery, Heart Ventricles, Vena Cava, Inferior, Tricuspid Valve Insufficiency, Pulmonary Valve Insufficiency, Echocardiography, Heart Atria, Heart Failure, Hemodynamics, Endarterectomy, Angioplasty, Balloon, Lung Diseases, United States Food and Drug Administration, Pulmonary Wedge Pressure, Endothelin Receptor Antagonists, Calcium Channel Blockers, Epoprostenol, Capillaries, Central Venous Catheters, Hypertension, Portal, Splenomegaly, Liver Cirrhosis, Pancytopenia, Registries, Dyspnea, Vascular Resistance, Vascular Resistance, Lung Transplantation, Hospitalization, Risk Assessment, Cardiac Catheterization, Connective Tissue Diseases, Gastrointestinal Diseases, Critical Care, World Health Organization


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