Characterisation of Pediatric Pulmonary Hypertensive Vascular Disease from the PPHNet Registry

2021 ◽  
pp. 2003337
Author(s):  
Steven H. Abman ◽  
Mary P. Mullen ◽  
Lynn A. Sleeper ◽  
Eric D. Austin ◽  
Erika B. Rosenzweig ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Natural History ◽  
Therapeutic Interventions ◽  
Patient Registries ◽  
Optimal Care ◽  
Genetic Syndrome ◽  
Common Group ◽  
Group 3 ◽  
Clinical Phenotyping ◽  
Group 1

BackgroundThere are limited data about the range of diseases, natural history, age-appropriate endpoints and optimal care for children with pulmonary hypertension (PH), including the need for developing high quality patient registries of children with diverse forms of PH to enhance care and research.ObjectiveTo characterise the distribution and clinical features of diseases associated with pediatric PH, including natural history, evaluation, therapeutic interventions and outcomes, as defined by the WSPH Classification.Methods1475 patients were enrolled into a multisite registry across the Pediatric Pulmonary Hypertension Network (PPHNet), comprised of 8 interdisciplinary PH programs.ResultsWSPH Groups 1 (PAH) and 3 (lung disease) were the most common primary classifications (45% and 49% of subjects, respectively). The most common Group 3 conditions were BPD and CDH. Group 1 disease was predominantly associated with congenital heart disease (60%) and idiopathic (23% of Group 1 cases). In comparison with Group 1, Group 3 subjects had better disease resolution (HR=3.1, p<0.001), tended to be younger at diagnosis (0.3 (0.0,0.6) versus 1.6 (0.1,6.9) years (median (IQR); p<0.001), and were more often male (57% versus. 45%, p<0.001). Down syndrome (DS), the most common genetic syndrome in the registry, constituted 11% of the entire PH cohort.ConclusionsWe find a striking proportion of pediatric PH patients with Group 3 disorders, reflecting the growing recognition of PH in diverse developmental lung diseases. Greater precision of clinical phenotyping based on disease-specific characterization may further enhance care and research of pediatric PH.

scholarly journals How is juvenile rheumatic heart disease different: baseline results from a prospective north Indian registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Mahajan ◽  
D.R Prakash Chand Negi
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Funding Source ◽  
Thromboembolic Events ◽  
Group 3 ◽  
Group 2 ◽  
Rheumatic Heart ◽  
Group 1

Abstract Introduction Juvenile rheumatic heart disease (RHD) refers to RHD in patients &lt;20 years of age. There are no contemporary data highlighting the differences between juvenile and older RHD patients. Purpose We aim to report the age related differences in the pattern, and consequencies of valvular dysfunction in patients of RHD. Methods The 2475 consecutive patients of RHD diagnosed using clinical and echocardiographic criteria were registered prospectively from 2011 till December 2019. Patients were divided into 3 groups according to their age: Group 1 (Juvenile RHD), Group 2 (21–50 years), and Group 2 (&gt;51 years).The data concerning the socio-demographic and clinical profile were recorded systematically, and the nature and severity of valvular dysfunction was assessed by echocardiography. The data were analyzed using the Epi-InfoTM Software. Results Out of 2475 RHD patients, Juvenile RHD comprised of 211 (8.5%) patients. Group 2 and 3 comprised of 1691 (68.3%) and 573 (23.2%) patients respectively. Overall, 1767 (71.4%) patients were females, however this female predilection was less pronounced in juvenile RHD (55.5% females vs 44.5% males) as compared to older groups. Past history of acute rheumatic fever was more commonly recorded in Juvenile RHD group (37.9% vs 18.8% in group 2 and 10% in group 3, p=0.0001). At the time of registration, the presence of advanced heart failure symptoms (dyspnea class III and IV) (11.4% group 1 vs 13.9% group 2 vs 20.6% group 3, p&lt;0.0001), right heart failure symptoms (0.9% group 1 vs 2.5% group 2 vs 7.3% group 3, p&lt;0.01), thromboembolic events (0% group 1 vs 4.1% group 2 vs 3.3% group 3, p&lt;0.01), atrial fibrillation (2.8% group 1 vs 24.5% group 2 vs 45.9% group 3, p&lt;0.0001), and pulmonary hypertension (27.1% group 1 vs 40.3% group 2 vs 51.9% group 3, p&lt;0.01), were all more commonly recorded in non-juvenile older RHD groups. Multivalvular involvement was also less common in juvenile RHD (34.6% vs 42.4% and 44.5%, p=0.04). Mitral regurgitation was the most common lesion in Juvenile RHD followed by aortic regurgitation (68.7% and 40.2% respectively). Stenotic lesions (both mitral and aortic) were present more commonly in older age groups. Conclusion RHD is predominantly a disease of females, however the predilection is less common in juvenile patients. Juvenile RHD predominantly affects the mitral valve and mainly leads to regurgitant lesions. As the age advances, the complications of RHD, mainly heart failure symptoms, thromboembolic events, pulmonary hypertension, and atrial fibrillation, become more common. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Self sponsored registry

Abstract 16078: Pulmonary Vasculopathy Assessed By Intravascular Ultrasound in Persistent Pulmonary Hypertension After Mitral Valve Replacement, Comparation to Idiopathic Pulmonary Arterial Hypertension and Healthy Controls

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Juan Carlos J Grignola ◽  
Leticia L Fernandez-Lopez ◽  
Enric E Domingo-Ribas ◽  
Rio R Aguilar ◽  
Cristian Humberto C Arredondo ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Elastic Modulus ◽  
Mitral Valve ◽  
Valve Replacement ◽  
Mitral Valve Replacement ◽  
Persistent Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Purpose: The aim of the study is to assess pulmonary vasculopathy (wall fibrosis, pulmonary arterial pulsatility and elastic modulus ) in patients with persistent pulmonary hypertension (pulmonary systolic pressure by ECHO > 50 mmhg ) at least 1 year after mitral valve replacement with normal function of the valve. The evaluation was carried out by intravascular ultrasound (IVUS) in medium sized pulmonary arteries. We compared three groups: Group 1 ( persistent pulmonary hypertension after mitral valve replacement), Group 2 (pulmonary hypertension belonging to the group 1 of the Dana Point classification) and Group 3 (healthy controls). Methods: We studied 43 patients, 15 in Group 1 , 18 Group 2 and 10 in Group 3. Group 1: 13 females, the mean age of this group was 74+-7 years; Group 2: 14 females, 53+-14 years and Group 3: 6 females, 51+-5 years. All patients were submitted to left and right heart catheterization, and IVUS in medium sized elastic PA ( 2-3 mm diameter ) of the inferior lobes. Studied variables were: mean pulmonary artery pressure (PAP, mm Hg), pulmonary wedge pressure, aortic pressure, cardiac output (CO,l/min), pulmonary vascular resistance (PVR, Wood Units), IVUS pulsatility and elastic modulus (EM,mm Hg). Local pulsatility was estimated by IVUS: (systolic- diastolic lumen area/ diastolic lumen area) X 100. PA stiffness was assessed by the elastic modulus (EM= pulse pressure/ IVUSp). Results: In Group 3 all variables were statistically different from the other 2 groups (p<0.01). Variables are shown in table. Conclusions: Group 1, even with a lower mean PAP than Group 2 (p<0.05) showed a similar anatomical ( wall fibrosis ) and similar functional wall remodeling ( EM ).

1409Use of phenomapping to determine response of treatment by sacubitril/valsartan in patients with heart failure with reduced ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Godet ◽  
O Raitiere ◽  
H Chopra ◽  
P Guignant ◽  
C Fauvel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Heat Map ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Treatment by sacubitril/valsartan decreases mortality, improves KCCQ score and ejection fraction in patients with heart failure with reduced ejection fraction (HF REF), but there is currently no data to predict response to treatment. Purpose The purpose of our work was to assess whether unbiased clustering analysis, using dense phenotypic data, could identify phenotypically distinct HF-REF subtypes with good or no response after 6 months of sacubitril/valsartan administration. Methods A total of 78 patients in NYHA functional class 2–3 and treated by ACE inhibitor or AAR2, were prospectively assigned to equimolar sacubitril/valsartan replacement. We collected demographic, clinical, biological and imaging continuous variables. Phenotypic domains were imputed with 5 eigenvectors for missing value, then filtered if the Pearson correlation coefficient was >0.6 and standardized to mean±SD of 0±1. Thereafter, we used agglomerative hierarchical clustering for grouping phenotypic variables and patients, then generate a heat map (figure 1). Subsequently, participants were categorized using Penalized Model-Based Clustering. P<0,05 was considered significant. Results Mean age was 60.4±13.4 yo and 79.0% patients were males. Mean ejection fraction was 29.3±7.0%. Overall, 16 phenotypic domains were isolated (figure 1) and 3 phenogroups were identified (Table 1). Phenogroup 1 was remarkable by isolated left ventricular involvement (LVTDD 64.3±5.9mm vs 73.9±8.7 in group 2 and 63.8±5.7 in group3, p<0.001) with moderate diastolic dysfunction (DD), no mitral regurgitation (MR) and no pulmonary hypertension (PH). Phenogroups 2 and 3 corresponded to patients with severe PH (TRMV: 2.93±0.47m/s in group 2 and 3.15±0.61m/s in groupe 3 vs 2.16±0.32m/s in group 1), related to severe DD (phenogroup 2) or MR (phenogroup 3). In both phenogroups, the left atrium was significantly enlarged and the right ventricle was remodeled, compared with phenogroup 1. Despite more severe remodeling and more compromised hemodynamic in phenogroups 2 and 3, the echocardiographic response to sacubitril/valsartan was comparable in all groups with similar improvement of EF and reduction of cardiac chambers dimensions (response of treatment, defined by improvement of FE +15% and/or decreased of indexed left ventricule diastolic volume −15% = group 2: 22 (76%); group 3: 18 (60%); group 1: 9 (50%); p=0.17; OR group 2 vs 1: OR=3.14; IC95% [0.9–11.03]; p=0.074; OR group 3 vs 1: OR=1.5; IC95% [0.46–4.87]; p=0.5)). The clinical response was even better in phenogroups 2 and 3 (Group 2: 19 (66%); group 3: 21 (78%) vs group 1: 9 (50%); p=0.05). Heat map Conclusion HF-REF patients with severe diastolic dysfunction, significant mitral regurgitation and elevated pulmonary hypertension by echocardiographic had similar reverse remodeling but better clinical improvement than patients with isolated left ventricular systolic dysfunction.

scholarly journals P1505 Echocardiographic assessment of different pulmonary hypertension groups

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M Fontes Oliveira ◽  
M Trepa ◽  
R Costa ◽  
A Dias Frias ◽  
I Silveira ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Interventricular Septum ◽  
Pulmonary Vascular Disease ◽  
Eccentricity Index ◽  
Group 4 ◽  
Global Strain ◽  
Group 3 ◽  
Group 2 ◽  
Rv Function ◽  
Group 1

Abstract Introduction Noninvasive echocardiography evaluation of the right ventricle (RV) has been shown to have prognostic value in patients with pulmonary hypertension (PH). Different etiology groups might have different echocardiographic phenotypes. In this study, we aimed to study echocardiographic characterization of the different PH groups and its ability to predict pulmonary vascular disease severity. Methods We collected echocardiographic and right heart catheterization (RHC) data from 97 (75% female, age 65 ± 15 years) consecutive patients referred to an expert tertiary care referral PH centre from 12/2016 to 11/2018. Echocardiographic analysis was performed using Echo-Pac software from GE Healthcare®. Group 3 and 5 were not included in the group comparison analysis due to few patients included. Results Group 2 PH was the most frequent etiology of PH (35), followed by group 1 (26), group 4 (18), group 5 (3) and group 3 (2). The echocardiographic evaluation of this population as a whole showed borderline parameters of RV dysfunction (tricuspid annular plane systolic excursion (TAPSE) 18 ± 4 mm, fractional area change (FAC) 33 ± 10% and S’ tricuspid wave 10 ± 3 cm/sec). Mean RV global strain was -15 ± 5 and RV free wall strain was -17 ± 7. PH group 1 had a significantly lower FAC (26 ± 4%, p = 0.0025), higher eccentricity index (IE) (1.5 ± 0.1, p = 0.01), and more frequently RV outflow tract (RVOT) notching than other groups (62%, p = 0.012). Group 4 presented an intermedium echocardiographic phenotype between group 1 and 2, and showed more abnormal strain values than the other groups. Group 2 had fewer patients in sinus rhythm (atrial fibrillation in 34% of patients, p = 0.02), presented a thicker interventricular septum (11.3 ± 1.8, p = 0.014), a higher FAC (35 ± 3%, p = 0.0025), higher E mitral wave velocity (72 ± 6 cm/s, p &lt; 0.001) and E/E’ ratio (12.7 ± 10.2, p = 0.006), and larger left (45 ± 3 cm3/m3, p &lt; 0.01) and right atria (25 ± 2 cm2, p = 0.03). PH groups 1 and 4 had higher Pulmonary Vascular Resistance (PVR) and Pulmonary Mean Arterial Pressure (PMAP) values than group 2, which significantly correlated with echocardiographic RV function parameters as TAPSE, FAC, RV global strain and IE. In PH group 2, eccentricity index was the only predictor of PVR (β=4.1, p = 0.018). In this population, a left atria volume &lt; 32.7 cm3/m2 (OR 4.25, CI 1.71 - 10.55) and a E/e’ ratio &lt; 12 (OR 4.72, CI 2.05 - 10.87) predicted PECP &lt; 15 mmHg. RV global strain &gt; -17.1 predicted PVR &gt; 3 wood (OR 3.46, CI 1.50 - 8.02) and PMAP &gt; 20 mmHg (OR 4.92, CI 1.67 - 14.51). TAPSE &lt; 18 mm predicted PVR &gt; 3 wood (OR 7.41, CI 2.99 - 18.36, AUC 0.72). Conclusion Different PH groups present mild echocardiographic differences between them. PH group 1 presented with more echocardiographic signs of RV disfunction, and PH group 2 had higher FAC, E/E’ and larger right and left atria. RV function parameters predicted PVR in PH groups 1 and 4, and EI was the only predictor of PVR in PH group 2. Abstract P1505 Figure.

scholarly journals Non-Group 1 Pulmonary Hypertension Associated With Systemic Sclerosis: An Under-studied Patient Population

2017 ◽  
Vol 16 (2) ◽  
pp. 68-75
Author(s):  
Zafia Anklesaria ◽  
Rajeev Saggar ◽  
Ariss Derhovanessian ◽  
Rajan Saggar
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
World Health ◽  
Response To Treatment ◽  
Specific Therapy ◽  
Pulmonary Manifestations ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Background: Systemic sclerosis (SSc) is a heterogeneous disorder that results in multiorgan dysfunction. The most common pulmonary manifestations are pulmonary hypertension (PH) and interstitial lung disease (ILD). Systemic sclerosis may be complicated by World Health Organization (WHO) Group 1 PH (SSc-PAH), which is the most well-studied subtype. The PH associated with SSc may also be secondary to underlying left heart disease (SSc-PH-LHD) or ILD (SSc-PH-ILD), and these subgroups are classified as WHO Group 2 and Group 3 PH, respectively. These non-WHO Group 1 PH subsets are notoriously under-studied. Available data suggest that the impact of PH-specific therapy in SSc-PH-LHD and SSc-PH-ILD is limited and survival is poor despite attempted treatment. Implication for clinicians: Most research and clinical trials surrounding PH in SSc have thus far focused on WHO Group 1 SSc-PAH. There are limited data surrounding therapeutic options for WHO Group 2 (SSc-PH-LHD) and Group 3 PH (SSc-PH-ILD) phenotypes. This review aims to summarize and consolidate the data surrounding these 2 distinct clinical phenotypes and to emphasize the available prognostic and treatment considerations. Conclusions: Given the unique pathophysiology, prognostic implications, and poor response to treatment of WHO Group 2 and 3 SSc-PH phenotypes, there is an overwhelming need for more data to best understand optimal management strategies. The focus should be individual patient-level prognostication, how and when to initiate and manage PH-specific therapy, and appropriate triage with regard to the timing of lung (or heart-lung) transplantation.

scholarly journals Peripheral Arterial Stiffness in Acute Pulmonary Embolism and Pulmonary Hypertension at Short-Term Follow-Up

2021 ◽  
Vol 10 (14) ◽  
pp. 3008
Author(s):  
Silvia Papa ◽  
Cristiano Miotti ◽  
Giovanna Manzi ◽  
Gianmarco Scoccia ◽  
Federico Luongo ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Pulmonary Hypertension ◽  
Arterial Stiffness ◽  
Hospital Discharge ◽  
Acute Pulmonary Embolism ◽  
Systemic Hypertension ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe and under-recognized complication of acute pulmonary embolism (PE). Forty consecutive patients with acute PE (Group 1), predominantly female (22, 55%) with a mean age of 69 ± 15 years, were matched for demographic data with 40 healthy subjects (Group 2), 40 systemic hypertension patients (Group 3) and 45 prevalent idiopathic pulmonary arterial hypertension (IPAH) patients (Group 4). The baseline evaluation included physical examination, NYHA/WHO functional class, right heart catheterization (RHC) limited to IPAH patients, echocardiographic assessment and systemic arterial stiffness measurement by cardio-ankle vascular index (CAVI). Patients with PE underwent an echocardiographic evaluation within 1 month from hospital discharge (median 27 days; IQR 21–30) to assess the echo-derived probability of PH. The CAVI values were significantly higher in the PE and IPAH groups compared with the others (Group 1 vs. Group 2, p < 0.001; Group 1 vs. Group 3, p < 0.001; Group 1 vs. Group 4, p = ns; Group 4 vs. Group 2, p < 0.001; Group 4 vs. Group 3, p < 0.001; Group 2 vs. Group 3, p = ns). The predicted probability of echocardiography-derived high-risk criteria of PH increases for any unit increase of CAVI (OR 9.0; C.I.3.9–20.5; p = 0.0001). The PE patients with CAVI ≥ 9.0 at the time of hospital discharge presented an increased probability of PH. This study highlights a possible positive predictive role of CAVI as an early marker for the development of CTEPH.

scholarly journals The Challenge to Decide between Pulmonary Hypertension Due to Chronic Lung Disease and PAH with Chronic Lung Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 311
Author(s):  
Horst Olschewski
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Disease ◽  
Chronic Lung Disease ◽  
Diagnostic Procedures ◽  
Disease Group ◽  
Group 4 ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Chronic lung diseases are strongly associated with pulmonary hypertension (PH), and even mildly elevated pulmonary arterial pressures are associated with increased mortality. Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease, but few of these patients develop severe PH. Not all these pulmonary pressure elevations are due to COPD, although patients with severe PH due to COPD may represent the largest subgroup within patients with COPD and severe PH. There are also patients with left heart disease (group 2), chronic thromboembolic disease (group 4, CTEPH) and pulmonary arterial hypertension (group 1, PAH) who suffer from COPD or another chronic lung disease as co-morbidity. Because therapeutic consequences very much depend on the cause of pulmonary hypertension, it is important to complete the diagnostic procedures and to decide on the main cause of PH before any decision on PAH drugs is made. The World Symposia on Pulmonary Hypertension (WSPH) have provided guidance for these important decisions. Group 2 PH or complex developmental diseases with elevated postcapillary pressures are relatively easy to identify by means of elevated pulmonary arterial wedge pressures. Group 4 PH can be identified or excluded by perfusion lung scans in combination with chest CT. Group 1 PAH and Group 3 PH, although having quite different disease profiles, may be difficult to discern sometimes. The sixth WSPH suggests that severe pulmonary hypertension in combination with mild impairment in the pulmonary function test (FEV1 > 60 and FVC > 60%), mild parenchymal abnormalities in the high-resolution CT of the chest, and circulatory limitation in the cardiopulmonary exercise test speak in favor of Group 1 PAH. These patients are candidates for PAH therapy. If the patient suffers from group 3 PH, the only possible indication for PAH therapy is severe pulmonary hypertension (mPAP ≥ 35 mmHg or mPAP between 25 and 35 mmHg together with very low cardiac index (CI) < 2.0 L/min/m2), which can only be derived invasively. Right heart catheter investigation has been established nearly 100 years ago, but there are many important details to consider when reading pulmonary pressures in spontaneously breathing patients with severe lung disease. It is important that such diagnostic procedures and the therapeutic decisions are made in expert centers for both pulmonary hypertension and chronic lung disease.

scholarly journals Pulmonary hypertension in chronic lung diseases: comparison to other pulmonary hypertension groups

2018 ◽  
Vol 8 (2) ◽  
pp. 204589401877505 ◽  
Author(s):  
Nader Chebib ◽  
Jean-François Mornex ◽  
Julie Traclet ◽  
François Philit ◽  
Chahera Khouatra ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Pulmonary Hypertension ◽  
Transfer Coefficient ◽  
Nyha Class ◽  
Univariate Analysis ◽  
Group 4 ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 5 ◽  
Group 1

Group 3 pulmonary hypertension (PH) is a common complication of advanced chronic lung disease. Our hypothesis was that group 3 PH is associated with a more severe baseline presentation and a more severe prognosis compared to group 1 pulmonary arterial hypertension (PAH), chronic thromboembolic PH (group 4), and group 5 PH. We retrospectively analyzed consecutive incident PH patients in a single center between January 2006 and November 2014. Data were acquired from a prospective database. Clinical, functional, and hemodynamic characteristics, as well as survival, were compared between the four groups of precapillary PH. A total of 363 patients were analyzed; 164 patients (45.2%) belonged to group 1 PAH, 109 (30%) to group 3 PH, 65 (17.9%) to group 4 PH, and 25 (6.9%) to group 5 PH. Group 3 patients were predominantly male and were more frequently in New York Heart Association (NYHA) class III/IV. Patients with group 3 and 4 PH were older, had significantly lower 6-min walking distance (6MWD), higher mean pulmonary arterial pressure, higher pulmonary vascular resistance (PVR), and lower cardiac index (CI) than PAH patients. Group 3 and 5 patients had significantly lower total lung capacity (TLC), forced vital capacity (FVC), and FEV1; group 3 patients had the lowest carbon monoxide transfer coefficient values. PH therapy was used in 90.9% of group 3 patients. Univariate analysis of prognostic factors in the overall population showed that age, male gender, NYHA class, groups 3 and 4 PH (vs. PAH), 6MWD, FVC, TLC, carbon monoxide transfer coefficient (KCO), PVR, CI, and venous oxygen saturation were significantly associated with greater mortality. Multivariate analysis showed that age, PH group 4, 6MWD, and KCO but no longer PH group 3 were significantly associated with mortality. Patients with group 3 PH are older, have more severe baseline presentation and lower survival rates than PAH patients in univariate analysis, that seemed to be related to older age.

Genetic differences based on miRNAs of colorectal adenocarcinoma according to age and the presence or absence of MMR defect.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 495-495
Author(s):  
Carmen Guillen-Ponce ◽  
ELISA Conde Moreno ◽  
Elia Aguado ◽  
Jl Soto ◽  
Cristina Alenda ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Colonic Mucosa ◽  
Colon Adenocarcinoma ◽  
Differentially Expressed ◽  
Therapeutic Interventions ◽  
Molecular Signature ◽  
Sporadic Cases ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

495 Background: More than 1.2 million new cases of colon adenocarcinoma (CRC) are diagnosed annually. Specific germline mutations are responsible for hereditary CRC syndromes, while somatic mutations is thought to underlie most sporadic cases. Recently, miRNAs have been described as important regulators of malignant transformation. We aim to study the expression of miRNAs in CRC patients with Lynch syndrome and in patients with CRC without microsatellite instability (MSI-S) who have developed cancer at different ages. Methods: We included 60 cases of CRC patients: 20 with CRC associated with Lynch syndrome in carriers of germline MMR mutation (group 1), 20 with CRC MSI-S diagnosed before 45 years (group 2) and 20 with MSI-S diagnosed after age 50 (group 3). From all these cases we selected 7: 3 from group 1, 2 from group 2, another 2 from group 3, and a control with healthy colonic mucosa. Screening was carried out for expression of miRNAs (850 miRNAs) and hybridization arrays (Exiqon) using paraffin colic tissue. A comparative analysis was made of the expression obtained in the different groups. Results: Hybridization arrays analysis indicates that there are 248 miRNAs differentially expressed between healthy controls and patients with CRC. In addition, there are 165 miRNAs differentially expressed between different groups of patients with CRC according to age at diagnosis (≤ 45 years vs.> 50 years). Moreover, the pattern of miRNAs in patients with germline mutation in Lynch syndrome is very different to that of patients diagnosed with CRC> 50 years. There are 117 miRNAs differentially expressed between these cases. Just a group of 20 miRNAs have different expression among patients with CRC MSI-S ≤ 45 years for CRC patients with Lynch syndrome mutation in MLH1. Conclusions: Differences exist in the profile of CRC mRNAs expression according to the age, as well as between CRC MSI-S patients > 50 years and CRC in Lynch syndrome. Different patterns of miRNAs in CRC indicate different molecular signature in different groups of CRC could became new CRC diagnostic markers and most importantly could point out new targets for therapeutic interventions in CRC.

scholarly journals Pulmonary hypertension in systemic sclerosis: different phenotypes

2017 ◽  
Vol 26 (145) ◽  
pp. 170056 ◽  
Author(s):  
David Launay ◽  
Vincent Sobanski ◽  
Eric Hachulla ◽  
Marc Humbert
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Lung Disease ◽  
Pulmonary Arteries ◽  
Left Ventricular ◽  
High Prevalence ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Pulmonary hypertension (PH) is a frequent and severe complication of systemic sclerosis (SSc). PH in SSc is highly heterogeneous because of the various clinical phenotypes of SSc itself and because the mechanisms of PH can vary from one patient to another. PH in SSc may be due to vasculopathy of the small pulmonary arteries (group 1; pulmonary arterial hypertension), interstitial lung disease (group 3; PH due to lung disease or chronic hypoxia) or myocardial fibrosis leading to left ventricular systolic or diastolic dysfunction (group 2; PH due to chronic left-heart disease). Pulmonary veno-occlusive disease is not uncommon in SSc and may also cause PH in some patients (group 1′). There is a high prevalence of each of these conditions in SSc and, as such, it may be difficult to determine the dominant cause of PH in a particular patient. However, careful phenotyping of PH in SSc is important as the therapy required for each of these underlying conditions is very different. In this review, we will decipher the different phenotypes of SSc-PH.

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