Impact de la pression artérielle et influence de l’insuffisance cardiaque systolique sur le contrôle de la fibrillation auriculaire et la survie

La pression artérielle est un déterminant potentiellement majeur de l’évolution de pathologies telles que la FA et l’insuffisance cardiaque. Pourtant, il demeure plusieurs incertitudes quant à la prise en charge optimale de la pression artérielle chez ces patients. Le rôle potentiel de la pression artérielle sur l’efficacité du maintien en rythme sinusal est inconnu. De plus, en présence d’insuffisance cardiaque, non seulement une pression artérielle élevée, mais aussi une pression artérielle basse pourrait augmenter la mortalité. Les travaux présentés ont pour but d’évaluer l’impact de la pression artérielle sur l’efficacité du contrôle du rythme et la mortalité ainsi que d’évaluer le rôle potentiel de l’insuffisance cardiaque sur cette interaction. Une étude post-hoc utilisant une banque de données combinant les études AFFIRM et AF-CHF a été réalisée. Les patients ont d’abord été classés selon leur FEVG (>40%, ≤40%), puis nous avons évalué l’impact de la PAS (140 mmHg) sur les issues. Premièrement, chez les 2715 patients randomisés au contrôle du rythme, nous avons évalué la survie sans récidive de FA. Deuxièmement, chez tous les 5436 patients inclus dans les 2 études sources, nous avons évalué la mortalité et la morbidité. Chez les patients avec FEVG >40%, aucune des issues n’a été affectée par la PAS dans des analyses de régression multivariées de Cox. Par contraste, chez les patients avec FEVG ≤40%, le taux de récidive de FA était plus élevé avec une PAS >140 mmHg et une PAS 140 mmHg et une PAS <120 mmHg [HR 1.75; IC 95% (1.41-2.17)] et [HR 1.40; IC 95% (1.04-1.90)], respectivement. En conclusion, le maintien en rythme sinusal et la survie sont influencés par la PAS chez les patients avec FA et FEVG diminuée, mais non chez les patients avec FEVG normale. Une courbe en forme de U a été identifiée, où les pression plus basses (140 mmHg) sont associées à un moins bon pronostic.Blood pressure may have a major impact on the evolution of AF and heart failure; nonetheless optimal management of blood pressure in these patients remains uncertain. Sinus rhythm maintenance has only moderate efficacy in abrogating AF and the potential role of blood pressure and its impact on risks of arrhythmia recurrence are unknown. Moreover, in patients with heart failure, blood pressure may affect prognosis in a non-linear fashion, where high blood pressure and also low blood pressure may increase mortality. The aim of this research was to evaluate the impact of blood pressure on the efficacy of sinus rhyhtm maintenance and mortality in patients with AF and to assess the potential role of ejection fraction and heart failure on this interaction. We conducted a post hoc combined analysis on pooled data from AFFIRM and AF-CHF trials. Patients were first classified according to LVEF (>40%, ≤40%) and we then assessed the impact of a baseline SBP (140 mmHg) on outcomes. Firstly, in a total of 2715 patients randomized to rhythm control, 68±8 years and followed for 41±17 months, we assessed time to first AF recurrence according to SBP. Secondly, in all 5436 patients from both source studies, we assessed mortality according to SBP. In patients with LVEF >40%, baseline SBP did not influence any of the outcomes in multivariate Cox regression analyses. In contrast, in patients with LVEF ≤40%, the AF recurrence rate was higher in those with a SBP 140 mmHg compared to SBP 120-140 mmHg [HR 1.15; 95% CI (0.92-1.43)] and [HR, 1.47; 95% CI (1.12-1.93)], respectively. Mortality was also modulated by blood pressure in patients with LVEF ≤40% : SBP 140 mmHg were both associated with increased death rate compared to SBP 120-140 mmHg [HR 1.75; 95% CI (1.41 to 2.17)] and [HR 1.40; 95% CI (1.04 to 1.90)], respectively. In conclusion, AF recurrence and mortality are influenced by SBP in patients with AF and depressed ejection fraction but not in patients with normal ejection fraction. A “U-shaped” pattern was identified where lower (140 mmHg) SBP lead to worse outcomes

Genome wide SNP comparative analysis between EGFR and KRAS mutated NSCLC and characterization of two models of oncogenic cooperation in non-small cell lung carcinoma

<p>Abstract</p> <p>Background</p> <p>Lung cancer with EGFR mutation was shown to be a specific clinical entity. In order to better understand the biology behind this disease we used a genome wide characterization of loss of heterozygosity and amplification by Single Nucleotide Polymorphism (SNP) Array analysis to point out chromosome segments linked to <it>EGFR </it>mutations. To do so, we compared genetic profiles between <it>EGFR </it>mutated adenocarcinomas (ADC) and <it>KRAS </it>mutated ADC from 24 women with localized lung cancer.</p> <p>Results</p> <p>Patterns of alterations were different between <it>EGFR </it>and <it>KRAS </it>mutated tumors and specific chromosomes alterations were linked to the <it>EGFR </it>mutated group. Indeed chromosome regions 14q21.3 (p = 0.027), 7p21.3-p21.2 (p = 0.032), 7p21.3 (p = 0.042) and 7p21.2-7p15.3 (p = 0.043) were found significantly amplified in EGFR mutated tumors. Within those regions 3 genes are of special interest <it>ITGB8</it>, <it>HDAC9 </it>and <it>TWIST1</it>. Moreover, homozygous deletions at <it>CDKN2A </it>and LOH at <it>RB1 </it>were identified in <it>EGFR </it>mutated tumors. We therefore tested the existence of a link between EGFR mutation, CDKN2A homozygous deletion and cyclin amplification in a larger series of tumors. Indeed, in a series of non-small-cell lung carcinoma (n = 98) we showed that homozygous deletions at <it>CDKN2A </it>were linked to <it>EGFR </it>mutations and absence of smoking whereas cyclin amplifications (<it>CCNE1 </it>and <it>CCND1</it>) were associated to <it>TP53 </it>mutations and smoking habit.</p> <p>Conclusion</p> <p>All together, our results show that genome wide patterns of alteration differ between <it>EGFR </it>and <it>KRAS </it>mutated lung ADC, describe two models of oncogenic cooperation involving either <it>EGFR </it>mutation and <it>CDKN2A </it>deletion or cyclin amplification and <it>TP53 </it>inactivating mutations and identified new chromosome regions at 7p and 14q associated to EGFR mutations in lung cancer.</p

Table_1_Thirty-year trends and outcome of isolated versus combined group 2 pulmonary hypertension after cardiac transplantation.DOCX

AimTo investigate the effect of the new definition of pulmonary hypertension (PH) and new pulmonary vascular resistance (PVR) thresholds on the prevalence, clinical characteristics, and events following cardiac transplantation (CTx) over 30 years.MethodsPatients who underwent CTx between 1983 and 2014 for whom invasive hemodynamic data was available were analyzed (n = 342). Patients transplanted between 1983 and 1998 were classified as early era and those transplanted between 1999 and 2014 were classified as recent era. Group 2 PH was diagnosed in the presence of a mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary capillary wedge pressure (PCWP) > 15 mmHg. Isolated post capillary PH (Ipc-PH) was defined as PVR ≤ 2 wood units and combined pre and post capillary PH (Cpc-PH) was defined PVR > 2 wood units. Moderate to severe PH was defined as mPAP ≥ 35 mmHg. The primary outcome was 30-day mortality and long-term mortality according to type and severity of PH. Proportions were analyzed using the chi-square test, and survival analyses were performed using Kaplan-Meier curves and compared using the logrank test.ResultsThe prevalence of PH in patients transplanted in the early era was 89.1%, whilst 84.2% of patients transplanted in the recent era had PH (p = 0.3914). There was no difference in the prevalence of a pre-capillary component according to era (p = 0.4001), but severe PH was more common in the early era (51.1% [early] vs 38.0% [recent] p = 0.0151). Thirty-day and long-term  mortality  were  not  significantly  associated  with severity or type of PH. There was a trend toward increased 30-day mortality in mild PH (10.1%), compared to no PH (4.4%) and moderate to severe PH (6.6%; p = 0.0653). Long-term mortality did not differ according to the severity of PH (p = 0.1480). There were no significant differences in 30-day or long-term mortality in IpcPH compared to CpcPH (p = 0.3974 vs p = 0.5767, respectively).ConclusionOver 30 years, PH has remained very prevalent before CTx. The presence, severity, and type (pre- vs post-capillary) of PH is not significantly associated with short- or long-term mortality.</p

Table_2_Thirty-year trends and outcome of isolated versus combined group 2 pulmonary hypertension after cardiac transplantation.DOCX

AimTo investigate the effect of the new definition of pulmonary hypertension (PH) and new pulmonary vascular resistance (PVR) thresholds on the prevalence, clinical characteristics, and events following cardiac transplantation (CTx) over 30 years.MethodsPatients who underwent CTx between 1983 and 2014 for whom invasive hemodynamic data was available were analyzed (n = 342). Patients transplanted between 1983 and 1998 were classified as early era and those transplanted between 1999 and 2014 were classified as recent era. Group 2 PH was diagnosed in the presence of a mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary capillary wedge pressure (PCWP) > 15 mmHg. Isolated post capillary PH (Ipc-PH) was defined as PVR ≤ 2 wood units and combined pre and post capillary PH (Cpc-PH) was defined PVR > 2 wood units. Moderate to severe PH was defined as mPAP ≥ 35 mmHg. The primary outcome was 30-day mortality and long-term mortality according to type and severity of PH. Proportions were analyzed using the chi-square test, and survival analyses were performed using Kaplan-Meier curves and compared using the logrank test.ResultsThe prevalence of PH in patients transplanted in the early era was 89.1%, whilst 84.2% of patients transplanted in the recent era had PH (p = 0.3914). There was no difference in the prevalence of a pre-capillary component according to era (p = 0.4001), but severe PH was more common in the early era (51.1% [early] vs 38.0% [recent] p = 0.0151). Thirty-day and long-term  mortality  were  not  significantly  associated  with severity or type of PH. There was a trend toward increased 30-day mortality in mild PH (10.1%), compared to no PH (4.4%) and moderate to severe PH (6.6%; p = 0.0653). Long-term mortality did not differ according to the severity of PH (p = 0.1480). There were no significant differences in 30-day or long-term mortality in IpcPH compared to CpcPH (p = 0.3974 vs p = 0.5767, respectively).ConclusionOver 30 years, PH has remained very prevalent before CTx. The presence, severity, and type (pre- vs post-capillary) of PH is not significantly associated with short- or long-term mortality.</p

Approaching Higher Dimension Imaging Data Using Cluster-Based Hierarchical Modeling in Patients with Heart Failure Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality, accounting for the majority of heart failure (HF) hospitalization. To identify the most complementary predictors of mortality among clinical, laboratory and echocardiographic data, we used cluster based hierarchical modeling. Using Stanford Translational Research Database, we identified patients hospitalized with HFpEF between 2005 and 2016 in whom echocardiogram and NT-proBNP were both available at the time of admission. Comprehensive echocardiographic assessment including left ventricular longitudinal strain (LVLS), right ventricular function and right ventricular systolic pressure (RVSP) was performed. The outcome was defined as all-cause mortality. Among patients identified, 186 patients with complete echocardiographic assessment were included in the analysis. The cohort included 58% female, with a mean age of 78.7 ± 13.5 years, LVLS of -13.3 ± 2.5%, an estimated RVSP of 38 ± 13 mmHg. Unsupervised cluster analyses identified six clusters including ventricular systolic-function cluster, diastolic-hemodynamic cluster, end-organ function cluster, vital-sign cluster, complete blood count and sodium clusters. Using a stepwise hierarchical selection from each cluster, we identified NT-proBNP (standard hazard ratio [95%CI] = 1.56 [1.17-2.08]) and RVSP (1.37 [1.09-1.78]) as independent correlates of outcome. When adding these parameters to the well validated Get with the Guideline Heart Failure risk score, the Chi-square was significantly improved (p = 0.01). In conclusion, NT-proBNP and RVSP were independently predictive in HFpEF among clinical, imaging, and biomarker parameters. Cluster-based hierarchical modeling may help identify the complementally predictive parameters in small cohorts with higher dimensional clinical data.status: publishe

AubinEtAl_CoVitas_ITV

Trait data collected for the CoVitas project that was used in the publication. Please see Metadata file for more details (in xlsx format

Geographic scale and disturbance influence intraspecific trait variability in leaves and roots of North American understorey plants

International audienceConsidering intraspecific trait variability (ITV) in ecological studies has improved our understanding of species persistence and coexistence. These advances are based on the growing number of leaf ITV studies over local gradients, but logistical constraints have prevented a solid examination of ITV in root traits or at scales reflecting species' geographic ranges. We compared the magnitude of ITV in above- and below-ground plant organs across three spatial scales (biophysical region, locality and plot). We focused on six understorey species (four herbs and two shrubs) that occur both in disturbed and undisturbed habitats across boreal and temperate Canadian forests. We aimed to document ITV structure over broad ecological and geographical scales by asking: (a) What is the breadth of ITV across species range-scale? (b) What proportion of ITV is captured at different spatial scales, particularly when local scale disturbances are considered? and (c) Is the variance structure consistent between analogous leaf and root traits, and between morphological and chemical traits? Following standardized methods, we sampled 818 populations across 79 forest plots simultaneously, including disturbed and undisturbed stands, spanning four biophysical regions (similar to 5,200 km). Traits measured included specific leaf area (SLA), specific root length (SRL) and leaf and root nutrient concentrations (N, P, K, Mg, Ca). We used variance decomposition techniques to characterize ITV structure across scales. Our results show that an important proportion of ITV occurred at the local scale when sampling included contrasting environmental conditions resulting from local disturbance. A certain proportion of the variability in both leaf and root traits remained unaccounted for by the three sampling scales included in the design (36% on average), with the largest amount for SRL (54%). Substantial differences in magnitude of ITV were found among the six species, and between analogous traits, suggesting that trait distribution was influenced by species strategy and reflects the extent of understorey environment heterogeneity. Even for species with broad geographical distributions, a large proportion of within-species trait variability can be captured by sampling locally across ecological gradients. This has practical implications for sampling design and trait selection for both local studies and continental-scale modelling. A plain language summary is available for this article