scholarly journals Genomics of Pulmonary Hypertension

2021 ◽  
Vol 20 (5) ◽  
pp. 142-149
Author(s):  
Carrie Lynn Welch ◽  
Wendy K. Chung
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Genome Sequencing ◽  
Clinical Management ◽  
Premature Mortality ◽  
Genetic Subtype ◽  
Associated Conditions ◽  
Pulmonary Arterial ◽  
Group 1

Background - Pulmonary hypertension (PH), defined by mean pulmonary artery pressure >20 mmHg, is a common physiologic manifestation of many diseases. Pulmonary arterial hypertension (PAH) represents a smaller subgroup of patients who have PH, and PAH causes significant cardiorespiratory morbidity and premature mortality. PH can manifest across the lifespan, with similar incidence for both pediatric- and adult-onset disease. However, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung and heart developmental anomalies. For PH Group 1/pulmonary arterial hypertension, causal genetic variants can be identified in ~13% of adults and ~43% of children. Clinical implications – Education about the option for genetic testing is strongly recommended for all pediatric and adult HPAH/IPAH patients. Both gene panel and exome/genome sequencing tests can be useful in diagnosis, but exome/genome sequencing provides a comprehensive dataset for reanalysis over time for cases without an initial diagnosis. Knowledge of genetic diagnoses can immediately impact clinical management of PH, including multimodal medical treatment, surgical intervention, transplantation decisions, and screening for associated conditions. Conclusions - There is a need for large, diverse, international consortia with ever-improving analytical pipelines to confirm previously implicated genes, identify additional genes/variants, assess penetrance, and clinically characterize each genetic subtype for natural history, prognosis and response to therapies to inform more precise clinical management.

Advanced Diagnosis and Therapy for Pulmonary Arterial Hypertension

Nano LIFE ◽  
2020 ◽  
Vol 10 (01n02) ◽  
pp. 2040003 ◽  
Author(s):  
Jing Qi ◽  
Yan Xing ◽  
Xiaoting Zhao ◽  
Daling Zhu ◽  
Xiaodong Zheng
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Progressive Disease ◽  
Task Force ◽  
Pulmonary Arteries ◽  
Premature Death ◽  
Pulmonary Arterial ◽  
Clinical Conditions ◽  
Group 1

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and progressive disease, which often leads to premature death. Pulmonary arterial hypertension (PAH, group 1 PH) comprises of diverse diseases that result in similar pathological changes, including the medium-sized pulmonary arteries and pulmonary arterioles characterized by vascular obliteration. The evaluation and diagnosis of PH and PAH were re-defined based on proceedings of the 6th World Symposia on Pulmonary Hypertension (WSPH). Accurate early diagnosis and subsequent therapy of PAH are necessary, as management of this disease is still challenging, and life expectancy is remaining suboptimal. This review task force reflects the multidisciplinary nature of PAH, including the definition, epidemiology, genetics, especially the advanced diagnosis and the therapy development in recent years.

scholarly journals PULMONARY HYPERTENSION STILL AN ‘ORPHAN LUNG DISEASE’ IN PAKISTAN

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Faisal Asad
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Heart Catheterization ◽  
Targeted Treatment ◽  
Heart Catheterization ◽  
Right Heart ◽  
Pulmonary Arterial ◽  
Group 1

In our country when it comes to diagnosis and treatment of Pulmonary Hypertension (PH) especially Pulmonary Arterial Hypertension (PAH), it seems that it is still an Orphan Lung disease. Whether it is data about its prevalence in our country, available diagnostic services or treatment options, one may easily feel the scarcity in all mentioned areas. Most current classification of PH, categorizes it into 5 groups.1 However this categorization requires availability of diagnostic tools especially right heart catheterization data to classify and know the severity of PH and to offer targeted treatment to patients who belong to group 1 PH i.e. Pulmonary Arterial Hypertension (PAH). Studies done about PH prevalence in Pakistan have mainly focused on data in selected patients group e.g. in patients with Chronic Obstructive Pulmonary Diseases (COPD) or Systemic Lupus Erythematosus (SLE).2,3 All of these studies relied on diagnosis without using the diagnostic bench mark i.e. Right heart catheterization. Moreover, effects of targeted treatment for PAH have also been studied only in selected group of patients e.g. COPD.4,5 While above work by the learned colleagues has to be appreciated, it emphasizes the need to, Spread the awareness about PH more so to reduce inadvertent use of targeted treatment which may prove detrimental outside group 1 PH and should only be considered at specialized centers. Develop specialized centers with required diagnostic services especially Lung functional and anatomical evaluation and Right heart catheterization. Establish PH registries (at least one in each province) which can play a vital role to collect data and ensure effective evidence based patient management. This may be an uphill task however the right direction to move forward.   REFERENCES Simonneau G, Montani D, David SC, Christopher PD, Michael AG, Michael K, at el. Paul G. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913. Amir S, Azmat A, Raza U, Hamid N, Zafar I, Shahida N, at el. Frequency of Pulmonary Hypertension in COPD patients. Pak J Chest Med. 2017;23(4):144-50. Sadia A, Aflak R, Tafazzul H, Ahmed A. Frequency and predictors of Pulmonary Hypertension in patients with SLE. Pak J Med Sci. 2019;35(1):86-9. Nasir H, Faisal F, Kausar R, Saadia A, Anjum N, Shafi K, at el. Efficacy of bosentan in the treatment of pulmonary hypertension; a prospective study focusing on safety and efficacy in patients with COPD. J Lung Pulm Respir Res. 2018;5(2):67-72. Sharieff S. Effect of sildenafil in primary pulmonary hypertension. Pak J Med Sci. 2007;23(2):264.

scholarly journals Residence at moderately high altitude and its relationship with WHO Group 1 pulmonary arterial hypertension symptom severity and clinical characteristics: the Pulmonary Hypertension Association Registry

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402096434
Author(s):  
Shoaib Fakhri ◽  
Kelly Hannon ◽  
Kelly Moulden ◽  
Ryan Peterson ◽  
Peter Hountras ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
High Altitude ◽  
Clinical Characteristics ◽  
Supplemental Oxygen ◽  
Walk Distance ◽  
Pulmonary Arterial ◽  
Low Altitude ◽  
Group 1

Background WHO Group 1 pulmonary arterial hypertension is a progressive and potentially fatal disease. Individuals living at higher altitude are exposed to lower barometric pressure and hypobaric hypoxemia. This may result in pulmonary vasoconstriction and contribute to disease progression. We sought to examine the relationship between living at moderately high altitude and pulmonary arterial hypertension characteristics. Methods Forty-two US centers participating in the Pulmonary Hypertension Association Registry enrolled patients who met the definition of WHO Group 1 pulmonary arterial hypertension. We utilized baseline data and patient questionnaire responses. Patients were divided into two groups: moderately high altitude residence (home ≥4000 ft) and low altitude residence (home <4000 ft) based on zip-code. Clinical characteristics, hemodynamic data, patient demographics, and patient reported quality of life metrics were compared. Results Controlling for potential confounders (age, sex at birth, body mass index, supplemental oxygen use, race, 100-day cigarette use, alcohol use, and pulmonary arterial hypertension medication use), subjects residing at moderately high altitude had a 6-min walk distance 32 m greater than those at low altitude, despite having a pulmonary vascular resistance that was 2.2 Wood units higher. Additionally, those residing at moderately high altitude had 3.7 times greater odds of using supplemental oxygen. Conclusion Patients with pulmonary arterial hypertension who live at moderately high altitude have a higher pulmonary vascular resistance and are more likely to need supplemental oxygen. Despite these findings, moderately high altitude Pulmonary Hypertension Association Registry patients have better functional tolerance as measured by 6-min walk distance. It is possible that a “high-altitude phenotype” of pulmonary arterial hypertension may exist. These findings warrant further study.

scholarly journals 0558 Sleep Disordered Breathing and Right Ventricular Electrocardiographic and Functional Characteristics in Group 1 Pulmonary Arterial Hypertension

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A214-A214
Author(s):  
A S Bhat ◽  
L Wang ◽  
S Kaur ◽  
R Nawabit ◽  
K Highland ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Sleep Disordered Breathing ◽  
Sleep Study ◽  
Unit Increase ◽  
Pulmonary Arterial ◽  
Group 1 ◽  
Disordered Breathing

Abstract Introduction Right ventricular (RV) electrophysiologic and functional alterations related to sleep disordered breathing (SDB) in pulmonary arterial hypertension (PAH) are not well understood. We hypothesize an association between SDB and RV electrophysiological/functional measures in World Symposium of Pulmonary Hypertension (WSPH) Group 1 PAH. Methods The NHLBI multicenter PVDOMICS study (NCT02980887) enrolls patients with PAH undergoing a battery of assessments including home sleep apnea testing(NOX-T3, Carefusion®) or with historical sleep study data. Logistic(OR,95%CI) and linear(beta coefficients,95%CI) regression models adjusted for age, sex, race, body mass index (BMI, kg/m2), PAH medications, supplemental oxygen(O2), positive airway pressure(PAP) were used to assess associations of SDB(apnea hypopnea index,(AHI), ≥3% desaturations(hypopnea), percentage recording time with SaO2&lt;90% (TRT&lt;90%) with electrocardiographic measures: RV hypertrophy(RVH), right bundle branch block(RBBB), and right axis deviation(RAD), echocardiographically-derived RV systolic pressure(RVSP) and RV ejection fraction(RVEF) from cardiac MRI. Analyses were performed based on an overall significance level of 0.05, using SAS software (version 9.4, Cary, NC). Results The analysis consisted of 182 PAH participants with age: 52.5±13.9 years, 71.4% female, 88.9% Caucasian, BMI:30.3±7.8 kg/m2, RVEF: 37.3±11.6, and RVSP: 67.0±23.4. None of the electrocardiographic measures were associated with AHI and only RVH was significantly associated with TRT&lt;90% (1.25:1.09,1.43),p=0.001. Although AHI was not associated with RVSP, a 10% increase in TRT&lt;90% was associated with a 2.60mmHg increase in RVSP (2.60:1.44,3.76),p&lt;0.001. Each 10-unit increase in AHI was associated with a 2.72% reduction of RVEF (-2.72:-4.89,-0.56),p=0.014, and each 10-unit increase in TRT&lt;90% was associated with a 0.72% reduction of RVEF (-0.72:-1.38,-0.06),p=0.033. Conclusion We identify nocturnal hypoxia as a predictor of RV electrophysiological and functional alterations even after consideration of confounding factors. SDB as determined by AHI was also more so associated with reduced RVEF than hypoxia. Future mechanistic studies should focus on further elucidation of SDB and nocturnal hypoxia on pathogenesis of RV dysfunction in PAH. Support U01HL125218/U01HL125205/U01HL125212/U01HL125208/U01HL125175/U01HL125215, U01HL125177/Pulmonary Hypertension Association

scholarly journals Idiopathic pulmonary arterial hypertension and co-existing lung disease: is this a new phenotype?

2020 ◽  
Vol 10 (1) ◽  
pp. 204589402091485 ◽  
Author(s):  
Andrew J. Peacock ◽  
Yi Ling ◽  
Martin K. Johnson ◽  
David G. Kiely ◽  
Robin Condliffe ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lung Disease ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Walk Distance ◽  
Pulmonary Arterial ◽  
Minute Walk Distance ◽  
Minute Walk ◽  
Group 1

Patients classified as idiopathic pulmonary arterial hypertension (defined as Group 1 on European Respiratory Society (ERS)/European Cardiac Society (ESC) criteria) may have evidence of minor co-existing lung disease on thoracic computed tomography. We hypothesised that these idiopathic pulmonary arterial hypertension patients ( IPAH lung disease) are a separate subgroup of idiopathic pulmonary arterial hypertension with different phenotype and outcome compared with idiopathic pulmonary arterial hypertension patients without co-existing lung disease ( IPAH no lung disease). Patients with ‘ IPAH lung disease’ have been eligible for all clinical trials of Group 1 patients because they have normal clinical examination and normal spirometry but we wondered whether they responded to treatment and had similar survival to patients with ‘ IPAH no lung disease’. We described the outcome of the cohort of patients with ‘ IPAH no lung disease’ in a previous paper. Here, we have compared incident ‘ IPAH lung disease’ patients with ‘ IPAH no lung disease’ patients diagnosed concurrently in all eight Pulmonary Hypertension centres in the UK and Ireland between 2001–2009. Compared with ‘ IPAH no lung disease’ ( n = 355), ‘ IPAH lung disease’ patients ( n = 137) were older, less obese, predominantly male, more likely to be current/ex-smokers and had lower six-minute walk distance, lower % predicted diffusion capacity for carbon monoxide, lower mean pulmonary arterial pressure and lower pulmonary vascular resistance index. After three months of pulmonary hypertension-targeted treatment, six-minute walk distance improved equally in ‘ IPAH lung disease’ and ‘ IPAH no lung disease’. However, survival of ‘ IPAH lung disease’ was lower than ‘ IPAH no lung disease’ (one year survival: 72% compared with 93%). This survival was significantly worse in ‘ IPAH lung disease’ even after adjusting for age, gender, smoking history, comorbidities and haemodynamics. ‘ IPAH lung disease’ patients had similar short-term improvement in six-minute walk distance with anti-pulmonary arterial hypertension therapy but worse survival compared with ‘ IPAH no lung disease’ patients. This suggests that ‘ IPAH lung disease’ are a separate phenotype and should not be lumped with ‘ IPAH no lung disease’ in clinical trials of Group 1 pulmonary arterial hypertension.

scholarly journals The role of pulmonary arterial hypertension-targeted therapy in systemic sclerosis

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 2124 ◽  
Author(s):  
Michael H Lee ◽  
Todd M Bull
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Targeted Therapy ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Systolic Function ◽  
World Health ◽  
Vascular Involvement ◽  
Pulmonary Arterial ◽  
Group 1

Pulmonary arterial hypertension, categorized as group 1 pulmonary hypertension by the World Health Organization classification system, represents a major complication of systemic sclerosis resulting from pulmonary vascular involvement of the disease. The high mortality seen in systemic sclerosis-associated pulmonary arterial hypertension is likely due to the impairment of right ventricular systolic function and the coexistence of other non-group-1 pulmonary hypertension phenotypes that may negatively impact clinical response to pulmonary arterial hypertension-targeted therapy. This review highlights two areas of recent advances regarding the management of systemic sclerosis patients with pulmonary hypertension: the tolerability of pulmonary arterial hypertension-targeted therapy in the presence of mild to moderate interstitial lung disease and the potential clinical significance of the antifibrotic effect of soluble guanylate cyclase stimulators demonstrated in preclinical studies.

scholarly journals Use of Pulmonary Arterial Hypertension–Approved Therapy in the Treatment of Non–Group 1 Pulmonary Hypertension at US Referral Centers

2015 ◽  
Vol 5 (2) ◽  
pp. 356-363 ◽  
Author(s):  
Aaron W. Trammell ◽  
Meredith E. Pugh ◽  
John H. Newman ◽  
Anna R. Hemnes ◽  
Ivan M. Robbins
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Arterial ◽  
Group 1

Pulmonary Arterial Hypertension: Epidemiology and Registries

2014 ◽  
Vol 13 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Michael D. McGoon ◽  
Marc Humbert
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Task Force ◽  
The World ◽  
Important Means ◽  
Pulmonary Arterial

Registries of pulmonary arterial hypertension (PAH) are important means by which to characterize the presentation and outcome of patients and to provide a basis for predicting the course of the disease. This article summarizes the published conclusions of the World Symposium of Pulmonary Hypertension task force that addressed registries and epidemiology of PAH.

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