Pulmonary hypertension (PH) is an end result of a diverse array of complex clinical conditions that invoke hemodynamic and pathophysiological changes in the pulmonary vasculature. Many patients’ symptoms begin with dyspnea on exertion for which screening tests such as chest roentgenograms and more definitive noninvasive tests such as CT scans are ordered initially. It is imperative that clinicians are cognizant of subtle clues on these imaging modalities that alert them to the possibility of PH. These clues may serve as a stepping stone towards more advanced noninvasive (echocardiogram) and invasive (right heart catheterization) testing. On the CT scan, the signs are classified into mediastinal and lung parenchymal abnormalities. In addition to suspecting the diagnosis of PH, this paper provides a pictorial essay to guide health care professionals in identifying the etiology of PH. This paper also provides concrete definitions, wherever possible, of what constitutes abnormalities in PH, such as dilated pulmonary arteries, pruning of vessels, and increased thickness of free wall of the right ventricle. The sensitivities and specificities of each sign are enumerated. The common radiographic and clinical features of many different etiologies of PH are tabulated for the convenience of the readers. Some newer imaging modalities such as dual-energy CT of the chest that hold promise for the future are also described.
Increased glycolysis in the lung vasculature has been connected to the development of pulmonary hypertension (PH). We therefore investigated whether glycolytic regulator 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase (PFKFB3)-mediated endothelial glycolysis plays a critical role in the development of PH. Heterozygous global deficiency of protected mice from developing hypoxia-induced PH, and administration of the PFKFB3 inhibitor 3PO almost completely prevented PH in rats treated with Sugen 5416/hypoxia, indicating a causative role of PFKFB3 in the development of PH. Immunostaining of lung sections and Western blot with isolated lung endothelial cells showed a dramatic increase in PFKFB3 expression and activity in pulmonary endothelial cells of rodents and humans with PH. We generated mice that were constitutively or inducibly deficient in endothelial and found that these mice were incapable of developing PH or showed slowed PH progression. Compared with control mice, endothelial -knockout mice exhibited less severity of vascular smooth muscle cell proliferation, endothelial inflammation, and leukocyte recruitment in the lungs. In the absence of , lung endothelial cells from rodents and humans with PH produced lower levels of growth factors (such as PDGFB and FGF2) and proinflammatory factors (such as CXCL12 and IL1β). This is mechanistically linked to decreased levels of HIF2A in lung ECs following knockdown. Taken together, these results suggest that targeting PFKFB3 is a promising strategy for the treatment of PH.
Anomalous origin of the pulmonary artery from the ascending aorta can lead to congestive heart failure in infancy, and with advancing age many patients will experience severe pulmonary hypertension. Surgical intervention has high mortality and morbidity risks if this happens. Strategies to manage these patients seem only limited to heart–lung transplantation or lung transplantation. Here, we successfully performed surgical intervention in an adult patient who had anomalous origin of the right pulmonary artery from the ascending aorta with high pressures in the ascending aorta and normally originating pulmonary artery.
To assess the demographics, treatment algorithm, and outcomes in a large cohort of children treated with sildenafil. A retrospective cohort study of children with pulmonary hypertension (PH) treated with sildenafil at a single institution between 2004 and 2015. Baseline and follow-up data collected by chart review. There were 269 children included in this study: 47 with idiopathic pulmonary arterial hypertension, 53 with congenital heart disease, 135 with bronchopulmonary dysplasia, 24 with congenital diaphragmatic hernia, and 7 with other causes. Sildenafil was initial monotherapy in 84.8% and add-on therapy in 15.2%. Median follow-up time was 3.1 years (2 weeks-12.4 years). On follow-up, 99 (37%) remained on sildenafil or transitioned to tadalafil, 93 (35%) stopped sildenafil for improvement in PH, 54 (20%) died, and 20 (7%) were lost to follow-up. PH was most likely to improve in those with bronchopulmonary dysplasia, allowing for the discontinuation of sildenafil in 45%. Eighteen deaths were related to PH and 36 from other systemic causes. Two patients stopped sildenafil owing to airway spasm with desaturation. Overall survival was significantly lower in World Health Organization group 3 PH (bronchopulmonary dysplasia and congenital diaphragmatic hernia) vs group 1 (idiopathic pulmonary arterial hypertension and congenital heart disease), = .02. In this retrospective experience in children with mainly World Health Organization groups 1 and 3 PH, low-dose sildenafil was well-tolerated, safe, and had an acceptable side effect profile. Although patients with group 3 PH have high mortality, survivors have a high likelihood of PH improving.
Significance: Pulmonary hypertension (PH) is a progressive disease characterized by pulmonary vascular remodeling and lung vasculopathy. The disease displays progressive dyspnea, pulmonary artery uncoupling and right ventricular (RV) dysfunction. The overall survival rate is ranging from 28–72%. Recent Advances: The molecular events that promote the development of PH are complex and incompletely understood. Metabolic impairment has been proposed to contribute to the pathophysiology of PH with evidence for mitochondrial dysfunction involving the electron transport chain proteins, antioxidant enzymes, apoptosis regulators, and mitochondrial quality control. Critical Issues: It is vital to characterize the mechanisms by which mitochondrial dysfunction contribute to PH pathogenesis. This review focuses on the currently available publications that supports mitochondrial mechanisms in PH pathophysiology. Future Directions: Further studies of these metabolic mitochondrial alterations in PH could be viable targets of diagnostic and therapeutic intervention.