Current Respiratory Medicine Reviews - Volume 20, Issue 3, 2024

While the majority of patients have complete resolution of their acute pulmonary embolism (PE) after an adequate course of anticoagulation, some patients remain symptomatic with evidence of chronic PE. Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Chronic Thromboembolic Pulmonary Disease (CTEPD) are terms that describe symptomatic patients with chronic thromboembolic occlusions of the pulmonary arteries with or without pulmonary hypertension, respectively. Here, we review the definitions, epidemiology, pathobiology, diagnosis and management of CTEPH. The chronic PE in CTEPH is essentially a scar in the pulmonary vasculature and is accompanied by a pulmonary arteriolar vasculopathy. Ventilation-perfusion scanning is the most sensitive screening test for CTEPH, and diagnosis must be confirmed by right heart catheterization (RHC). Treatment decisions require a multidisciplinary team and guidance from additional imaging, usually CT or pulmonary angiography. While pulmonary endarterectomy (PEA) to remove the chronic PE surgically is still the first-line treatment for appropriate candidates, there is an expanding role for balloon pulmonary angioplasty (BPA) and medical treatment, as well as multimodality treatment approaches that incorporate all of those options. New imaging modalities and treatment strategies hold the promise to improve our care and management of CTEPH patients in the future.

Group 5 pulmonary hypertension (PH) with unclear and/or multifactorial mechanisms includes a wide variety of conditions associated with PH, and the mechanisms by which PH develops vary dramatically depending on the underlying condition. Indeed, in many group 5 conditions, such as sarcoidosis, multiple distinct drivers of PH are present concurrently in a single patient, with the predominant factor depending on the predisposing disease phenotype. For this reason, thorough diagnostic evaluation to most accurately phenotype every patient with group 5 PH is essential. Treatment of these patients should begin by fully characterizing and optimizing the management of their underlying disease, often in conjunction with disease experts. Initial targets of PH treatment include identifying and correcting factors that worsen PH, such as volume overload and hypoxemia, as well as a complete PH evaluation, searching for other undiagnosed causes of PH (e.g., congenital heart disease or chronic thromboembolic disease). Data to guide treatment with therapies specific to pulmonary arterial hypertension (PAH) are inadequate for any specific recommendations, and adverse effects in group 5 patients are common. If these therapies are considered, evaluation by a multidisciplinary team that includes a PH specialist is recommended. Factors in the selection of PAH therapies should include consideration of the dominant physiologic features of the underlying disease, the severity of hemodynamic and right ventricular abnormalities, the risk of adverse drug effects, and any known contraindications to PAH-specific medications based on the underlying condition. Vigilant monitoring following initiation of PAH-specific therapy is critical, as the clinical effects are hard to predict, and untoward events, such as uncovering pulmonary veno-occlusive disease, may occur. Collaborative care by a multidisciplinary team of experts is key to the management of this challenging patient population.

Pulmonary Arterial Hypertension (PAH) is a progressive disease with no cure. A major determinant of outcome is the function of the right ventricle (RV). Unfortunately, progressive RV dysfunction and failure can occur despite PAH-specific therapies. While initial adaptive hypertrophic changes occur to maintain cardiac output and preserve contractile function and reserve, maladaptive changes occur in the RV muscle that contribute to RV systolic and diastolic dysfunction and failure. These include impaired angiogenesis / decreased capillary density with ischemia, fibrosis, cardiomyocyte apoptosis and impaired autophagy, inflammation, enhanced oxidative stress, altered metabolism, etc. Of note, there are no therapies currently approved that offset these changes and treatment of RV dysfunction is largely supportive only. Further patients often do not qualify for bilateral lung transplantation because of co-morbidities such as renal impairment. Thus, a dire unmet need exists regarding the management of RV dysfunction and failure in patients with PAH. In this State-of-the-Art review, we comprehensively outline the unique features of the RV compared to the left ventricle (LV) under normal circumstances and highlight the unique challenges faced by the RV when confronted with increased afterload as occurs in PAH. We provide detailed insights into the basis for the adaptive hypertrophic phase as well as detailed commentary into the pathophysiology of the maladapted dysfunctional state as well as the pathobiological aberrations occurring in the RV muscle that underlines the progressive dysfunction and failure that commonly ensues. We also review comprehensively the evaluation of RV function using all currently employed imaging, hemodynamic and other modalities and provide a balanced outline of strengths and limitations of such approaches with the treating clinician in mind. We outline the current approaches, albeit limited to chronic multi-modal management of RV dysfunction and failure. We further outline new possible approaches to treatment that include novel pharmacologic approaches, possible use of cellular/stem cell therapies and mechanical approaches. This review is directed to the treating clinician to provide comprehensive insights regarding the RV in patients with PAH.

Pulmonary hypertension is associated with worse outcomes across systemic and cardiopulmonary conditions. Right ventricular (RV) dysfunction often leads to poor outcomes due to a progressive increase in RV afterload. Recognition and management of RV dysfunction are important to circumvent hospitalization and improve patient outcomes. Early recognition of patients at risk for RV failure is important to ensure that medical therapy is optimized and, where appropriate, referral for lung transplant assessment is undertaken. Patients initiated on parenteral prostanoids and those with persistent intermediate to high risk for poor outcomes should be referred. For patients with RV failure, identifying reversible causes should be a priority in conjunction with efforts to optimize RV preload and strategies to reduce RV afterload. Admission to a monitored environment where vasoactive medications can treat RV failure and its sequelae, such as renal dysfunction, is essential in patients with severe RV failure. Exit strategies need to be identified early on, with consideration and implementation of extracorporeal support for those in whom recovery or transplantation are viable options. Enlisting the skills and support of a palliative care team may improve the quality of life for patients with limited options and those with ongoing symptoms from heart failure in the face of medical treatments.

Pulmonary hypertension in patients with congenital heart disease is associated with significant mortality, morbidity and health services utilization. The predominant subtype of pulmonary hypertension in these patients is pulmonary arterial hypertension (PAH). PAH associated with congenital heart disease (PAH-CHD) comprises up to one-third of all PAH cases globally and is most commonly associated with anatomically simple shunt lesions. A myriad of clinical phenotypes of PAH-CHD are seen across the spectrum of shunt size, location and directionality. A conceptual framework to categorize these patients based on pathophysiology is described. Contemporary data regarding the management of the varied phenotypes are reviewed, and a novel algorithm to guide decision-making with shunt closure in patients with PAH-CHD is provided. Further data spanning the spectrum of basic, translational and clinical science are much needed to further inform the management of this highly complex and heterogeneous population.

Pregnancy in patients with pulmonary arterial hypertension (PAH) is a high-risk condition associated with high morbidity and mortality. Patients with severe PAH are often advised against pregnancy. Still, those patients who pursue pregnancy require a dedicated and multidisciplinary approach since the progression of fetal growth will accompany significant hemodynamic changes, which can be challenging for patients with a poorly functioning right ventricle. In this article, we describe the approach to the unique cardiovascular, respiratory, hematologic, and social challenges that pregnant patients with PAH face throughout pregnancy. We discuss the impact of these physiologic changes on diagnostic studies commonly used in PAH and how to incorporate diagnostic data in making the diagnosis and risk stratifying pregnant patients with PAH. The pharmacologic challenges of pulmonary vasodilators in pregnancy are discussed as well. Pregnant patients with PAH are at particularly high risk of mortality around the time of delivery, and we discuss the multidisciplinary approach to the management of these patients, including the use of anesthesia, inotropic support, type of delivery, and postpartum care, providing clinicians with a practical approach to the management of this difficult condition.