Pre-Capillary, Combined, and Post-Capillary Pulmonary Hypertension

Opitz, Christian; Hoeper, Marius M.; Gibbs, J. Simon R.; Kaemmerer, Harald; Pepke‐Zaba, Joanna; Coghlan, J. Gerry; Scelsi, Laura; D′Alto, Michele; Olsson, Karen M.; Ulrich, Silvia; Scholtz, Werner; Schulz, Uwe; Grünig, Ekkehard; Vizza, Carmine Dario; Staehler, G.; Bruch, Leonhard; Huscher, Dörte; Pittrow, David; Rosenkranz, Stephan

doi:10.1016/j.jacc.2016.05.047

Cited by 265 publications

(252 citation statements)

References 28 publications

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“…This corroborates the findings of several (13,16,37), but not all (5,14) previous publications. The only study to demonstrate increased mortality in PH-LHD patients with a DPG ≥7 mm Hg evaluated Cpc-PH in 80 and 49 patients with systolic and diastolic heart failure, respectively (14).…”

Section: Discussionsupporting

confidence: 93%

Clinical and Biological Insights Into Combined Post- and Pre-Capillary Pulmonary Hypertension

Assad

Hemnes

Larkin

et al. 2016

Journal of the American College of Cardiology

169

201

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Background Pulmonary hypertension (PH) is a common and morbid complication of left heart disease with 2 subtypes: isolated post-capillary PH (Ipc-PH) and combined post-capillary and pre-capillary PH (Cpc-PH). Little is known about the clinical or physiological characteristics that distinguish these 2 subphenotypes, and if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH). Objectives We sought to test the hypothesis that the hemodynamic and genetic profile of Cpc-PH would more closely resemble PAH than Ipc-PH. Methods We used Vanderbilt’s electronic medical record linked to a DNA biorepository to extract demographics, clinical data, invasive hemodynamics, echocardiography, and vital status for all patients referred for right heart catheterization between 1998 and 2014. We identified shared genetic variants between PAH and Cpc-PH compared with Ipc-PH using pre-existing single-nucleotide polymorphism data. Results We identified 2,817 patients with PH (13% Cpc-PH, 52% Ipc-PH, and 20% PAH). Cpc-PH patients were on average 6 years younger, with more severe pulmonary vascular disease than Ipc-PH patients, despite similar comorbidities and prevalence, severity, and chronicity of left heart disease. After adjusting for relevant covariates, the risk of death was similar between Cpc-PH and Ipc-PH (HR: 1.14, 95% CI: 0.96 to 1.35, p = 0.15) when defined by diastolic pressure gradient. We identified 75 shared exonic single-nucleotide polymorphisms between Cpc-PH and PAH enriched in pathways involving cell structure, extracellular matrix, and immune function. These genes are expressed, on average, 32% higher in lungs relative to other tissues. Conclusions Cpc-PH patients develop pulmonary vascular disease similar to PAH patients, despite younger age and similar prevalence of obesity, diabetes mellitus, and left heart disease compared with Ipc-PH patients. An exploratory genetic analysis in Cpc-PH identified genes and biological pathways in the lung known to contribute to PAH pathophysiology, suggesting that Cpc-PH may be a distinct and highly morbid PH subphenotype.

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Section: Discussionsupporting

confidence: 93%

Clinical and Biological Insights Into Combined Post- and Pre-Capillary Pulmonary Hypertension

Assad

Hemnes

Larkin

et al. 2016

Journal of the American College of Cardiology

169

201

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“…Given that there is now ample evidence favouring the use of combination therapy in patients with PAH [10][11][12][13], and considering that the present ESC/ERS guidelines recommend initial combination therapy including intravenous prostacyclin for patients presenting at high risk [4,5], it is surprising to see that monotherapy was still used in the majority of patients. One potential reason for this reluctance may be the fact that the patients in the present series were relatively old; it is possible that the presence of comorbidities may have led physicians to prefer monotherapies [7,9]. In addition, the enrolment period for the present analysis started in 2009, when there was less evidence supporting the use of combination therapy in patients with PAH.…”

Section: Discussionmentioning

confidence: 98%

“…COMPERA applies a series of state-of-the-art quality checks including automated queries of out-of-range data, individual queries of data that raise concerns and independent on-site source data verification. Further details of COMPERA have been published elsewhere [7][8][9].…”

Section: Methodsmentioning

confidence: 99%

Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model

et al. 2017

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@ERSpublicationsThe risk stratification strategy proposed by the current European PH guidelines allows accurate survival prediction http://ow.ly/KsWk30c46nK ABSTRACT The 2015 European pulmonary hypertension (PH) guidelines propose a risk stratification strategy for patients with pulmonary arterial hypertension (PAH). Low-, intermediate-and high-risk strata are defined by estimated 1-year mortality risks of <5%, 5-10% and >10%, respectively. This risk assessment strategy awaits validation.We analysed data from patients with newly diagnosed PAH enrolled into COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension), a European-based PH registry. An abbreviated version of the risk assessment strategy proposed by the European PH guidelines was applied, using the following variables: World Health Organization functional class, 6-min walking distance, brain natriuretic peptide or its N-terminal fragment, right atrial pressure, cardiac index and mixed venous oxygen saturation.Data from 1588 patients were analysed. Mortality rates were significantly different between the three risk strata ( p<0.001 for all comparisons). In the entire patient population, the observed mortality rates 1 year after diagnosis were 2.8% in the low-risk cohort (n=196), 9.9% in the intermediate-risk cohort (n=1116) and 21.2% in the high-risk cohort (n=276). In addition, the risk assessment strategy proved valid at follow-up and in major PAH subgroups.An abbreviated version of the risk assessment strategy proposed by the current European PH guidelines provides accurate mortality estimates in patients with PAH.

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“…In addition, neutrophil/lymphocyte ratio seems to be increased among diabetic patients and in these it was also shown to be independently associated with cardiovascular events [23, 24]. The co-occurrence of cardiovascular risk factors has been increasingly observed alongside with a demographical shift towards older age in patients diagnosed with PAH who had entered clinical trials and registries [25]. This has led to the use of terms such as ‘atypical PAH’, which refers to patients who have 3 or more risk factors for left heart disease [25].…”

Section: Discussionmentioning

confidence: 99%

Exploratory analysis of the neutrophil to lymphocyte ratio in patients with pulmonary arterial hypertension

et al. 2017

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BackgroundChronic inflammation emerges as a feature of the pathogenesis of pulmonary arterial hypertension (PAH) in experimental models. Alterations of circulating cell subsets have been observed in patients with PAH. We aimed to assess associations of the white blood cell count with disease severity and outcome in patients with PAH.MethodsThe total and differential white blood cell count was related to functional parameters, pulmonary hemodynamics and transplantation-free survival in 77 patients with PAH in an observational single center study.ResultsAn increased neutrophil/lymphocyte ratio was associated with poor World Health Organization functional class and shorter 6-minute walking distance, as well as with elevated right atrial pressure and high level of N-terminal prohormone of brain natriuretic peptide. During a median follow-up period of 31 months (range 16-56) 23 patients died and 2 patients were referred to lung transplantation. Using uni- and subsequent bivariate Cox proportional hazards analyses an increased neutrophil/lymphocyte ratio was associated with unfavorable transplantation-free survival independent of hemodynamic parameters and C-reactive protein. The prognostic implication sustained in subsets of patients with incident PAH and in the absence of cardiovascular risk factors.ConclusionsThe results of this analysis indicate that a neutrophilic inflammation may be associated with clinical deterioration and poor outcome in patients with PAH. Assessing the composition of the differential white blood cell count may render prognostic information and could represent a step towards incorporating an inflammatory marker into the clinical management of patients with PAH.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-017-0407-5) contains supplementary material, which is available to authorized users.

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Pre-Capillary, Combined, and Post-Capillary Pulmonary Hypertension

Abstract: Patients with atypical IPAH share features of both typical IPAH and PH-HFpEF, suggesting that there may be a continuum between these conditions.

Cited by 265 publications

References 28 publications

Clinical and Biological Insights Into Combined Post- and Pre-Capillary Pulmonary Hypertension

Clinical and Biological Insights Into Combined Post- and Pre-Capillary Pulmonary Hypertension

Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model

Exploratory analysis of the neutrophil to lymphocyte ratio in patients with pulmonary arterial hypertension

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