scholarly journals Genotypes and Phenotypes: A Review of Pulmonary Hypertension in Genetic Syndromes

2021 ◽  
Vol 20 (5) ◽  
pp. 150-156
Author(s):  
Rachel T Sullivan ◽  
Eric D Austin
Keyword(s):  
Pulmonary Hypertension ◽  
Genetic Variants ◽  
Current Knowledge ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Pulmonary Vascular Disease ◽  
Disease Phenotype ◽  
Genetic Syndromes ◽  
High Prevalence ◽  
Pulmonary Arterial ◽  
Genetic Makeup

There has been significant advancement in the understanding of the genetics of pulmonary hypertension (PH), particularly in those with heritable or idiopathic pulmonary arterial hypertension. In addition to genetic variants with a primarily pulmonary vascular disease phenotype, the prevalence of PH in other genetic syndromes is increasingly recognized. We will review the current knowledge of PH associated with multisystem genetic syndromes. There is high prevalence of coexisting cardiac and pulmonary disease, making it challenging to discern whether PH is secondary to these processes or underlying genetic makeup. There is a paucity of data on response to PH-targeted therapy and implications on overall prognosis.

scholarly journals Heart and lung transplantation in pulmonary arterial hypertension related to congenital heart disease: an unusual indication

2020 ◽  
Vol 4 (S1) ◽  
Author(s):  
Rosaria Barracano ◽  
Heba Nashat ◽  
Andrew Constantine ◽  
Konstantinos Dimopoulos
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lung Transplantation ◽  
Atrial Septal Defect ◽  
Septal Defect ◽  
Pulmonary Vascular Disease ◽  
Eisenmenger Syndrome ◽  
Pulmonary Arterial ◽  
Recurrent Haemoptysis

Abstract Background Eisenmenger syndrome is a multisystem disorder, characterised by a significant cardiac defect, severe pulmonary hypertension and long-standing cyanosis. Despite the availability of pulmonary hypertension therapies and improved supportive care in specialist centres, Eisenmenger patients are still faced with significant morbidity and mortality. Case presentation We describe the case of a 44-year-old woman with Eisenmenger syndrome secondary to a large secundum atrial septal defect. Her pulmonary vascular disease was treated with pulmonary vasodilators, but she experienced a progressive decline in exercise tolerance, increasing atrial arrhythmias, resulting in referral for transplantation. Her condition was complicated by significant recurrent haemoptysis in the context of extremely dilated pulmonary arteries and in-situ thrombosis, which prompted successful heart and lung transplantation. She made a slow recovery but remains well 3 years post-transplant. Conclusions Patients with Eisenmenger syndrome secondary to a pre-tricuspid lesion, such as an atrial septal defect have a natural history that differs to patients with post-tricuspid shunts; the disease tends to present later in life but is more aggressive, prompting early and aggressive medical intervention with pulmonary arterial hypertension therapies. This case illustrates that severe recurrent haemoptysis can be an indication for expediting transplantation in Eisenmenger syndrome patients.

scholarly journals Idiopathic Pulmonary Arterial Hypertension Unmasked by Pregnancy

2020 ◽  
Vol 19 (4) ◽  
pp. 240-243
Author(s):  
Adam Maxwell ◽  
◽  
Thomas Holman ◽  
Timea Novak ◽  
◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Post Partum ◽  
Right Heart Failure ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Shortness Of Breath ◽  
Acute Medical Unit ◽  
Pulmonary Angiogram ◽  
Pulmonary Arterial

A 31-year old woman presented to the acute medical unit 9 days post-partum with shortness of breath and peripheral oedema. Initially suspected to have either a pulmonary embolism or post-partum cardiomyopathy, she proceeded to have imaging including a CT Pulmonary angiogram and echocardiogram, which were suggestive of pulmonary hypertension and severe right heart failure. Her history and other investigations did not reveal any obvious cause for this. She was transferred to a specialist centre where she was diagnosed with Idiopathic Pulmonary Arterial Hypertension (IPAH), previously known as primary pulmonary hypertension. Shortness of breath during pregnancy and in the postpartum period is a relatively common acute medical presentation. Whilst IPAH is a rare diagnosis, it carries a high mortality rate, particularly in pregnancy, and requires prompt specialist investigation, diagnosis and management.

scholarly journals Lower DLco% identifies exercise pulmonary hypertension in patients with parenchymal lung disease referred for dyspnea

2020 ◽  
Vol 10 (1) ◽  
pp. 204589401989191 ◽  
Author(s):  
Richard H. Zou ◽  
William D. Wallace ◽  
S. Mehdi Nouraie ◽  
Stephen Y. Chan ◽  
Michael G. Risbano
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Disease ◽  
Vascular Disease ◽  
Pulmonary Function Tests ◽  
Pulmonary Vascular Disease ◽  
Chronic Obstructive ◽  
Exertional Dyspnea ◽  
Pulmonary Arterial ◽  
Parenchymal Lung Disease ◽  
Parenchymal Lung

Exercise pulmonary hypertension is an underappreciated form of physical limitation related to early pulmonary vascular disease. A low diffusing capacity of lungs for carbon monoxide (DLco) can be seen in patients with resting pulmonary hypertension as well as parenchymal lung disease. It remains unclear whether low DLco% identifies early pulmonary vascular disease. We hypothesize that a reduced DLco% differentiates the presence of exercise pulmonary hypertension in patients with parenchymal lung disease. Fifty-six patients referred for unexplained exertional dyspnea with pulmonary function tests within six months of hemodynamic testing underwent exercise right heart catheterization. Exclusion criteria included resting pulmonary arterial or venous hypertension. Receiver operator characteristic curve determined the optimal DLco% cutoffs based on the presence or absence of parenchymal lung disease. Twenty-one (37%) patients had parenchymal lung disease, most common manifesting as chronic obstructive lung disease or interstitial lung disease. In patients with parenchymal lung disease, a DLco of 46% demonstrated 100% sensitivity and 73% specificity for detecting exercise pulmonary hypertension. In patients without parenchymal lung disease, a DLco of 73% demonstrated 58% sensitivity and 94% specificity for detecting exercise pulmonary hypertension. In both cohorts, DLco% below the optimum cutoffs were associated with higher peak mean pulmonary arterial pressure and peak total pulmonary resistance consistent with the hemodynamic definition of exercise pulmonary hypertension. Patients with a DLco < 46% were more often treated with pulmonary vasodilators and had a trend to higher mortality and lung transplant. DLco% is a simple non-invasive screening test for the presence of exercise pulmonary hypertension in our mixed referral population with progressive exertional dyspnea. DLco < 46% with parenchymal lung disease and DLco < 73% without parenchymal lung disease may play a role in differentiating the presence of pulmonary vascular disease prior to invasive hemodynamic testing.

scholarly journals Acute vasoreactivity testing in pediatric idiopathic pulmonary arterial hypertension: an international survey on current practice

2019 ◽  
Vol 9 (4) ◽  
pp. 204589401985753
Author(s):  
Lina Caicedo ◽  
Rachel Hopper ◽  
Humberto Garcia Aguilar ◽  
Dunbar Ivy ◽  
Dora Haag ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Functional Class ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Clinical Criteria ◽  
First Line Therapy ◽  
Specific Protocol ◽  
The World ◽  
Pulmonary Arterial

The aim of this study was to determine practice patterns and inter-institutional variability in how acute vasoreactivity testing (AVT) is performed and interpreted in pediatrics throughout the world. A survey was offered to physicians affiliated with the Pediatric & Congenital Heart Disease Taskforce of the Pulmonary Vascular Research Institute (PVRI), the Pediatric Pulmonary Hypertension Network (PPHNET), or the Spanish Registry for Pediatric Pulmonary Hypertension (REHIPED), from February to December 2016. The survey requested data about the site-specific protocol for AVT and subsequent management of pediatric patients with idiopathic pulmonary arterial hypertension (IPAH) or heritable PAH (HPAH). Twenty-eight centers from 13 countries answered the survey. AVT is performed in most centers using inhaled nitric oxide (iNO). Sitbon criteria was used in 39% of the centers, Barst criteria in 43%, and other criteria in 18%. First-line therapy for positive AVT responders in functional class (FC) I/II was calcium channel blocker (CCB) in 89%, but only in 68% as monotherapy. Most centers (71%) re-evaluated AVT-positive patients hemodynamics after 6–12 months; 29% of centers re-evaluated based only on clinical criteria. Most centers (64%) considered a good response as remaining in FC I or II, with near normalization of pulmonary arterial pressure and pulmonary vascular resistance, but a stable FC I/II alone was sufficient criteria in 25% of sites. Protocols and diagnostic criteria for AVT, and therapeutic approaches during follow-up, were highly variable across the world. Reported clinical practice is not fully congruent with current guidelines, suggesting the need for additional studies that better define the prognostic value of AVT for pediatric IPAH patients.

scholarly journals Genomewide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension

2010 ◽  
Vol 298 (4) ◽  
pp. H1235-H1248 ◽  
Author(s):  
Revathi Rajkumar ◽  
Kazuhisa Konishi ◽  
Thomas J. Richards ◽  
David C. Ishizawar ◽  
Andrew C. Wiechert ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Estrogen Receptor ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Rna Expression ◽  
Data Set ◽  
Platelet Factor ◽  
Protein Ubiquitination ◽  
Pulmonary Arterial

Idiopathic pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by pulmonary arteriolar remodeling. This investigation aimed to identify genes involved specifically in the pathogenesis of PAH and not other forms of pulmonary hypertension (PH). Using genomewide microarray analysis, we generated the largest data set to date of RNA expression profiles from lung tissue specimens from 1) 18 PAH subjects and 2) 8 subjects with PH secondary to idiopathic pulmonary fibrosis (IPF) and 3) 13 normal subjects. A molecular signature of 4,734 genes discriminated among these three cohorts. We identified significant novel biological changes that were likely to contribute to the pathogenesis of PAH, including regulation of actin-based motility, protein ubiquitination, and cAMP, transforming growth factor-β, MAPK, estrogen receptor, nitric oxide, and PDGF signaling. Bone morphogenic protein receptor type II expression was downregulated, even in subjects without a mutation in this gene. Women with PAH had higher expression levels of estrogen receptor 1 than normal women. Real-time quantitative PCR confirmed differential expression of the following genes in PAH relative to both normal controls and PH secondary to IPF: a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9, cell adhesion molecule with homology to L1CAM, cytochrome b558and β-polypeptide, coagulation factor II receptor-like 3, A-myb myeloblastosis viral oncogene homolog 1, nuclear receptor coactivator 2, purinergic receptor P2Y, platelet factor 4, phospholamban, and tropomodulin 3. This study shows that PAH and PH secondary to IPF are characterized by distinct gene expression signatures, implying distinct pathophysiological mechanisms.

scholarly journals Circulating Plasma Metabolomic Profiles Differentiate Rodent Models of Pulmonary Hypertension and Idiopathic Pulmonary Arterial Hypertension Patients

2019 ◽  
Vol 32 (11) ◽  
pp. 1109-1117
Author(s):  
Jun-Han Zhao ◽  
Yang-Yang He ◽  
Shan-Shan Guo ◽  
Yi Yan ◽  
Zhe Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Progressive Disease ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Rodent Models ◽  
Preclinical Models ◽  
Metabolic Dysregulation ◽  
Pulmonary Arterial ◽  
Significant Pathway

Abstract BACKGROUND Pulmonary arterial hypertension (PAH) is a severe progressive disease with systemic metabolic dysregulation. Monocrotaline (MCT)-induced and hypoxia-induced pulmonary hypertension (PH) rodent models are the most widely used preclinical models, however, whether or not these preclinical models recapitulate metabolomic profiles of PAH patients remain unclear. METHODS In this study, a targeted metabolomics panel of 126 small molecule metabolites was conducted. We applied it to the plasma of the 2 preclinical rodent models of PH and 30 idiopathic pulmonary arterial hypertension (IPAH) patients as well as 30 healthy controls to comparatively assess the metabolomic profiles of PAH patients and rodent models. RESULTS Significantly different metabolomics profiling and pathways were shown among the 2 classical rodent models and IPAH patients. Pathway analysis demonstrated that methionine metabolism and urea cycle metabolism were the most significant pathway involved in the pathogenesis of hypoxia-induced PH model and MCT-induced model, respectively, and both of them were also observed in the dysregulated pathways in IPAH patients. CONCLUSIONS These 2 models may develop PAH through different metabolomic pathways and each of the 2 classical PH model resembles IPAH patients in certain aspects.

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