Outcomes of patients with decreased arterial oxyhaemoglobin saturation on pulmonary arterial hypertension drugs.

BACKGROUND: Drugs approved for the treatment of pulmonary arterial hypertension (PAH) improve long-term outcomes. These drugs have pulmonary vasodilator properties which may potentially cause a decrease in arterial oxyhaemoglobin saturation (S aO2 ) in some patients. The present retrospective study of the French Pulmonary Hypertension Registry aimed to describe the clinical characteristics and outcomes of patients showing a ≥3% decrease in S aO2 while treated with PAH drugs. METHODS: We reviewed 719 PAH patients. The exclusion criteria were PAH associated with congenital heart disease and PAH with overt features of venous/capillaries involvement. RESULTS: 173 (24%) patients had a ≥3% decrease in S aO2 . At diagnosis, they were older with a lower diffusing capacity of the lung for carbon monoxide and a shorter 6-min walk distance compared with those who did not display a ≥3% decrease in S aO2 . The percentage of patients meeting the European Society of Cardiology/European Respiratory Society (ESC/ERS) low-risk criteria at re-evaluation was significantly lower in those with a ≥3% decrease in S aO2 and more patients started long-term oxygen therapy in this group (16% versus 5%; p<0.001). A ≥3% decrease in S aO2 was associated with a poorer survival (hazard ratio 1.81, 95% CI 1.43-2.34; p<0.0001). In a multivariate Cox analysis, a ≥3% decrease in S aO2 was a prognostic factor independent of age at diagnosis and ESC/ERS risk stratification at follow-up. CONCLUSIONS: When treated with PAH drugs, a large subset of patients experience a ≥3% decrease in S aO2 , which is associated with worse long-term outcomes and reduced survival.

Prognostic influence of acute decompensated heart failure in patients planned for transcatheter aortic valve implantation.

OBJECTIVE: The aim of our study was to evaluate the outcome of patients with severe aortic stenosis presenting with acute decompensated heart failure (ADHF) and planned for transcatheter aortic valve implantation (TAVI) and to study the variables influencing their prognosis. METHODS: Our retrospective study included 801 patients planned for TAVI in our center. Seven hundred and fifty-six underwent TAVI and were categorized according to ADHF as the initial clinical presentation into two groups: ADHF group (n = 261) and no-ADHF group (n = 495). Pre as well as periprocedural outcomes and 1 year mortality were analyzed. RESULTS: Among the patients planned for the TAVI procedure, 45 patients remained untreated: 35 patients died while waiting to undergo TAVI which represented 20% of all deaths in our study, ADHF was observed in 23 of 45 (51%) these untreated patients. The 1-year all-cause mortality rate was significantly higher in the ADHF group versus the no-ADHF group (27% vs. 15%, p < .0001). In multivariate analysis, male gender (odds ratio [OR] =2.5, 95% confidence interval [CI]: 1.37-4.57, p = .03), body mass index <25 kg/m2 (OR = 2.76, 95% CI: 1.51-5.04, p = .0009), and logistic EuroSCORE II ≥20% (OR = 3.04, 95% CI: 1.56-5.94, p = .001) were associated with a higher 1-year mortality in the ADHF group. CONCLUSION: The patients eligible for TAVI presenting with ADHF were associated with a higher mortality for both: while on the waiting list for TAVI as well as at 1-year follow-up and thus asking for clearer criteria to prioritize action in this high-risk TAVI patients.

Galectin-3 down-regulates antioxidant peroxiredoxin-4 in human cardiac fibroblasts: a new pathway to induce cardiac damage.

Galectin-3 (Gal-3) is increased in heart failure (HF) and promotes cardiac fibrosis and inflammation. We investigated whether Gal-3 modulates oxidative stress in human cardiac fibroblasts, in experimental animal models and in human aortic stenosis (AS). Using proteomics and immunodetection approaches, we have identified that Gal-3 down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. In parallel, Gal-3 increased peroxide, nitrotyrosine, malondialdehyde, and N-carboxymethyl-lysine levels and decreased total antioxidant capacity. Gal-3 decreased prohibitin-2 expression without modifying other mitochondrial proteins. Prx-4 silencing increased oxidative stress markers. In Gal-3-silenced cells and in heart from Gal-3 knockout mice, Prx-4 was increased and oxidative stress markers were decreased. Pharmacological inhibition of Gal-3 with modified citrus pectin restored cardiac Prx-4 as well as prohibitin-2 levels and improved oxidative status in spontaneously hypertensive rats. In serum from 87 patients with AS, Gal-3 negatively correlated with total antioxidant capacity and positively correlated with peroxide. In myocardial biopsies from 26 AS patients, Gal-3 up-regulation paralleled a decrease in Prx-4 and in prohibitin-2. Cardiac Gal-3 inversely correlated with Prx-4 levels in myocardial biopsies. These data suggest that Gal-3 decreased Prx-4 antioxidant system in cardiac fibroblasts, increasing oxidative stress. In pathological models presenting enhanced cardiac Gal-3, the decrease in Prx-4 expression paralleled increased oxidative stress. Gal-3 blockade restored Prx-4 expression and improved oxidative stress status. In AS, circulating levels of Gal-3 could reflect oxidative stress. The alteration of the balance between antioxidant systems and reactive oxygen species production could be a new pathogenic mechanism by which Gal-3 induces cardiac damage in HF.

Cardiac remodeling following reperfused acute myocardial infarction is linked to the concomitant evolution of vascular function as assessed by cardiovascular magnetic resonance.

BACKGROUND: Left ventricular (LV) remodeling following acute myocardial infarction (MI) is difficult to predict at an individual level although a possible interfering role of vascular function has yet to be considered to date. This study aimed to determine the extent to which this LV remodeling is influenced by the concomitant evolution of vascular function and LV loading conditions, as assessed by phase-contrast Cardiovascular Magnetic Resonance (CMR) of the ascending aorta. METHODS: CMR was performed in 121 patients, 2-4 days after reperfusion of a first ST-segment elevation myocardial infarction and 6 months thereafter. LV remodeling was: (i) assessed by the 6-month increase in end-diastolic volume (EDV) and/or ejection fraction (EF) and (ii) correlated with the indexed aortic stroke volume (mL.m-2), determined by a CMR phase-contrast sequence, along with derived functional vascular parameters (total peripheral vascular resistance (TPVR), total arterial compliance index, effective arterial elastance). RESULTS: At 6 months, most patients were under angiotensin enzyme converting inhibitors (86%) and beta-blockers (84%) and, on average, all functional vascular parameters were improved whereas blood pressure levels were not. An increase in EDV only (EDV+/EF-) was documented in 17% of patients at 6 months, in EF only (EDV-/EF+) in 31%, in both EDV and EF (EDV+/EF+) in 12% and neither EDV nor EF (EDV-/EF-) in 40%. The increase in EF was mainly and independently linked to a concomitant decline in TPVR (6-month change in mmHg.min.m2.L-1, EDV-/EF-: +1 ± 8, EDV+/EF-: +3 ± 9, EDV-/EF+: -7 ± 6, EDV+/EF+: -15 ± 20, p < 0.001) while the absence of any EF improvement was associated with high persisting rates of abnormally high TPVR at 6 months (EDV-/EF-: 31%, EDV+/EF-: 38%, EDV-/EF+: 5%, EDV+/EF+: 13%, p = 0.007). By contrast, the 6-month increase in EDV was mainly dependent on cardiac as opposed to vascular parameters and particularly on the presence of microvascular obstruction at baseline (EDV-/EF-: 37%, EDV+/EF-: 76%, EDV-/EF+: 38%, EDV+/EF+: 73%, p = 0.003). CONCLUSION: LV remodeling following reperfused MI is strongly influenced by the variable decrease in systemic vascular resistance under standard care vasodilating medication. The CMR monitoring of vascular resistance may help to tailor these medications for improving vascular resistance and consequently, LV ejection fraction. TRIAL REGISTRATION: NCT01109225 on ClinicalTrials.gov site (April, 2010).

Grey-Matter Metabolism in Relation with White-Matter Lesions in Older Hypertensive Patients with Subjective Memory Complaints: A Pilot Voxel-Based Analysis Study.

BACKGROUND: This study aimed at assessing the changes in brain metabolism related to white-matter magnetic resonance (MR) hyperintensities of presumed vascular origin, with a voxel-based quantitative analysis of (18F)-fluorodesoxyglucose positron emission tomography (FDG-PET) imaging. METHODS: Sixty older hypertensive patients with subjective memory complaints (75 ± 5 years, 34 women) were prospectively referred to FDG-PET and MRI brain imaging. The Statistical Parametric Mapping software was used to assess the correlation between brain distribution of FDG and white-matter hyperintensities assessed by the Fazekas score on MRI images. RESULTS: The Fazekas score was inversely related to FDG uptake, independently of age and gender, within 14 Brodmann areas located mainly in the frontal lobe but also in certain limbic, insular and temporal areas. This relationship was also found to be largely independent of the volume of grey matter expressed in percentage of cranial volume, an index of atrophy. CONCLUSIONS: White-matter MR hyperintensities of presumed vascular origin are cross-sectionally associated with a lower grey-matter metabolism, mainly but not only within frontal areas and independently of age, gender and grey-matter atrophy.

Predictive factors of brain death in severe stroke patients identified by organ procurement and transplant coordination in Lorrain, France.

There are no established predictive factors to identify patients at the acute phase of severe stroke with a high probability of presenting brain death (BD). We retrospectively collected clinical and paraclinical data of consecutive patients at the acute phase of severe stroke with a potential progression to BD through the hospital organ procurement and transplant coordination system in five centres in Lorrain (France) between 1 January 2012 and 31 December 2013. Final endpoint was adjudicated BD. Of 400 included patients, 91 (23%) presented adjudicated BD. Initial Glasgow Coma Scale score ≤6 (P = 0.008), herniation (P = 0.009), hydrocephalus (P = 0.019), initial systolic blood pressure >150 mmHg (P = 0.002), past history of alcohol abuse (P = 0.019) and stroke volume >65 ml (P = 0.040) were significantly associated with BD progression. Two prognostic scores for stroke with unquantifiable or quantifiable volume were built according to the number of risk factors presented. Following internal validation, the respective bias-corrected predictive performance (c-index) of the two scores was 72% (95% confidence interval: 67-78%) and 77% (95% confidence interval: 72-82%). These scores could form the basis of a simple tool of six criteria to help physicians make the difficult decision of intensive care unit management to preserve organs in potential donors.

Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis.

Heparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess non-inferiority of a heparin grafted dialyzer (NCT01318486). A total of 251 maintenance hemodialysis patients at increased risk of hemorrhage were randomly allocated for up to three heparin-free hemodialysis sessions using a heparin-grafted dialyzer or the center standard-of-care consisting of regular saline flushes or pre-dilution. The first heparin-free hemodialysis session was considered successful when there was neither complete occlusion of air traps or dialyzer, nor additional saline flushes, changes of dialyzer or bloodlines, or premature termination. The current standard-of-care resulted in high failure rates (50%). The success rate in the heparin-grafted membrane arm was significantly higher than in the control group (68.5% versus 50.4%), which was consistent for both standard-of-care modalities. The absolute difference between the heparin-grafted membrane and the controls was 18.2%, with a lower bound of the 90% confidence interval equal to plus 7.9%. The hypothesis of the non-inferiority at the minus 15% level was accepted, although superiority at the plus 15% level was not reached. Thus, use of a heparin-grafted membrane is a safe, helpful, and easy-to-use method for heparin-free hemodialysis in patients at increased risk of hemorrhage.

Factors affecting the myocardial activity acquired during exercise SPECT with a high-sensitivity cardiac CZT camera as compared with conventional Anger camera.

PURPOSE: Injected doses are difficult to optimize for exercise SPECT since they depend on the myocardial fraction of injected activity (MFI) that is detected by the camera. The aim of this study was to analyse the factors affecting MFI determined using a cardiac CZT camera as compared with those determined using conventional Anger cameras. METHODS: Factors affecting MFI were determined and compared in patients who had consecutive exercise SPECT acquisitions with (201)Tl (84 patients) or (99m)Tc-sestamibi (87 patients) with an Anger or a CZT camera. A predictive model was validated in a group of patients routinely referred for (201)Tl (78 patients) or (99m)Tc-sestamibi (80 patients) exercise CZT SPECT. RESULTS: The predictive model involved: (1) camera type, adjusted mean MFI being ninefold higher for CZT than for Anger SPECT, (2) tracer type, adjusted mean MFI being twofold higher for (201)Tl than for (99m)Tc-sestamibi, and (3) logarithm of body weight. The CZT SPECT model led to a +1 ± 26% error in the prediction of the actual MFI from the validation group. The mean MFI values estimated for CZT SPECT were more than twofold higher in patients with a body weight of 60 kg than in patients with a body weight of 120 kg (15.9 and 6.8 ppm for (99m)Tc-sestamibi and 30.5 and 13.1ppm for (201)Tl, respectively), and for a 14-min acquisition of up to one million myocardial counts, the corresponding injected activities were only 80 and 186 MBq for (99m)Tc-sestamibi and 39 and 91 MBq for (201)Tl, respectively. CONCLUSION: Myocardial activities acquired during exercise CZT SPECT are strongly influenced by body weight and tracer type, and are dramatically higher than those obtained using an Anger camera, allowing very low-dose protocols to be planned, especially for (99m)Tc-sestamibi and in non-obese subjects.

Coronary Embolism Among Patients With ST-Segment-Elevation Myocardial Infarction and Atrial Fibrillation: An Underrecognized But Deadly Association.

BACKGROUND: The prevalence and impact of coronary emboli (CE) in patients with ST-segment-elevation myocardial infarction (STEMI) and atrial fibrillation (AF) have not been specifically studied. The objective was to describe the clinical characteristics and outcomes of patients with AF and CE in a large series of patients with STEMI. METHODS AND RESULTS: We investigated 2292 consecutive patients with STEMI and among them 225 patients with AF: 46 patients with a STEMI related to CE (group A) and 179 patients with a STEMI related to an atherosclerotic cause (group B). Compared with the 2067 patients without AF and CE (group C), patients with AF and CE were older (73 versus 59 years, P<0.05), more likely to be female (43% versus 22%, P<0.05), and presented more frequently with cardiogenic shock at admission (26% versus 9%, P<0.05). The baseline characteristics of patients with AF (group A versus B) did not differ significantly according to STEMI pathogenesis. In the unadjusted analysis, the 45-day mortality was higher in patients with CE and AF (group A versus group C: 20% versus 4%; P<0.05 and group A versus group B: 20% versus 8%, P=not significant); this trend persisted at 2-year follow-up (group A versus group C: 24% versus 6%; P<0.05 and group A versus group B: 24% versus 17%, P=not significant). After stabilized inverse exposure probability weighting adjustment, a higher 45-day mortality rate was confirmed in patients with CE and AF (group A versus group C: 18% versus 5%, P<0.05). CONCLUSIONS: In patients presenting with STEMI and AF, CE was associated with excess early mortality. REGISTRATION: URL: clinicaltrials.gov. Identifier: NCT05679843.

Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study.

BACKGROUND: We evaluated the effect of the selective mineralocorticoid receptor antagonist eplerenone on renal function and the interaction between changes in renal function and subsequent cardiovascular outcomes in patients with heart failure and left ventricular systolic dysfunction after an acute myocardial infarction in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). METHODS AND RESULTS: Serial changes in estimated glomerular filtration rate (eGFR) were available in 5792 patients during a 24-month follow-up. Patients assigned to eplerenone had a decline in eGFR with an adjusted mean difference of -1.4±0.3 mL · min(-1) · 1.73 m(-2) compared with placebo (P<0.0001), an effect that appeared within the first month (-1.3±0.4 mL · min(-1) · 1.73 m(-2)) and persisted throughout the study. Overall, 914 patients experienced a decline in eGFR >20% in the first month, 16.9% and 14.7% in the eplerenone and placebo groups, respectively (odds ratio, 1.15; 95% confidence interval, 1.02-1.30; P=0.017). In multivariate analyses, determinants of this early decline in eGFR were female sex, age ≥65 years, smoking, left ventricular ejection fraction <35%, and use of eplerenone and loop diuretic. An early decline in eGFR by >20% was associated with worse cardiovascular outcomes independently of baseline eGFR and of the use of eplerenone, which retained its prognostic benefits even under these circumstances. CONCLUSIONS: In patients with heart failure after acute myocardial infarction and receiving standard medical care, an early decline in eGFR is not uncommon and is associated with poor long-term outcome. Eplerenone induced a moderately more frequent early decline in eGFR, which did not affect its clinical benefit on cardiovascular outcomes.

Comparison between stress myocardial perfusion SPECT recorded with cadmium-zinc-telluride and Anger cameras in various study protocols.

PURPOSE: The results of stress myocardial perfusion SPECT could be enhanced by new cadmium-zinc-telluride (CZT) cameras, although differences compared to the results with conventional Anger cameras remain poorly known for most study protocols. This study was aimed at comparing the results of CZT and Anger SPECT according to various study protocols while taking into account the influence of obesity. METHODS: The study population, which was from three different institutions equipped with identical CZT cameras, comprised 276 patients referred for study using protocols involving (201)Tl (n = 120) or (99m)Tc-sestamibi injected at low dose at stress ((99m)Tc-Low; stress/rest 1-day protocol; n = 110) or at high dose at stress ((99m)Tc-High; rest/stress 1-day or 2-day protocol; n = 46). Each Anger SPECT scan was followed by a high-speed CZT SPECT scan (2 to 4 min). RESULTS: Agreement rates between CZT and Anger SPECT were good irrespective of the study protocol (for abnormal SPECT, (201)Tl 92 %, (99m)Tc-Low 86 %, (99m)Tc-High 98 %), although quality scores were much higher for CZT SPECT with all study protocols. Overall correlations were high for the extent of myocardial infarction (r = 0.80) and a little lower for ischaemic areas (r = 0.72), the latter being larger on Anger SPECT (p < 0.001). This larger extent was mainly observed in 50 obese patients who were in the (201)Tl or (99m)Tc-Low group and in whom stress myocardial counts were particularly low with Anger SPECT (228 ± 101 kcounts) and dramatically enhanced with CZT SPECT (+279 ± 251 %). CONCLUSION: Concordance between the results of CZT and Anger SPECT is good regardless of study protocol and especially when excluding obese patients who have low-count Anger SPECT and for whom myocardial counts are dramatically enhanced on CZT SPECT.

Flexible intramedullary nailing in children: nail to medullary canal diameters optimal ratio.

BACKGROUND: Postoperative axial deviations and delayed unions are possible complications after flexible intramedullary nailing (FIN). The goals of this study were to determine if a correlation exists between occurrence of the above complications and the ratio of the diameter between nail and medullary canal [nail diameter (ND)/MCD ratio], to study the interobserver variability in the measurement of MCD, and to define a threshold to be respected to optimize the results. METHODS: Eighty-one consecutive diaphyseal fractures treated by means of FIN were evaluated. The ND/MCD ratios were determined by 2 independent observers. Axial deviations were defined as 5-degree angulation or more observed before bone union. Absence of bone union at 3 months was considered as delayed union. Statistical analysis was made for interobserver variability of MCD, dependency between occurrence of complications and ND/MCD ratio and eventual confounding variables (age, weight, sex, and fracture location). RESULTS: Of the 81 fractures, 14 presented with an axial deviation and 3 with a delayed union. Interobserver variability of MCD diameter was excellent (intraclass correlation: 0.96). Occurrence of the above complications was significantly associated with a low ND/MCD ratio (P=0.0002) but with none of the examined confounding variables. Receiver operating characteristic analysis showed absence of complications with a ND/MCD ratio >35% with a sensitivity of 100% and specificity of 89%. Related with the MCD measurements variability, a safe threshold of 40% can be suggested. CONCLUSIONS: In FIN, ND>40% to the MCD should be chosen to avoid complications, besides respecting the technical principles. Measuring the medullary canal diameter in order to choose correct nail size is reproducible between different observers. In adolescents with a medullary canal diameter of >10 mm in femur or tibia fractures, alternative methods of osteosynthesis than FIN should be considered. SIGNIFICANCE: This work statistically confirms that a ND/MCD ratio of >40% must be respected to avoid some complications in FIN. LEVEL OF EVIDENCE: Level III.

Impact of Simulation-Based Training on Radiation Exposure of Young Interventional Cardiologists.

Reducing radiation exposure during cardiovascular catheterization is of paramount importance to ensure patient and staff safety. Our study aimed to assess the transferability of acquired skills from virtual reality to the real world, including radioprotection measures during mentored simulation training (ST) in coronary angiography. A total of 10 cardiology residents were evaluated during real-life cases in the catheterization laboratory before (group A) and after mentored ST. The educational effect of mentored simulator training on real-life case performance was evaluated at 2 different time points: within the first week (group B) and after 12 weeks (group C). Compared with group A, the total dose area product (DAP) (µGy•m2) and total air kerma (mGy) were lower after ST: group A: 2,633 (1,723 to 3,617) versus group B: 1,618 (1,032 to 2,562), p <0.05 and 214 (136 to 297) versus 135 (84 to 222), p <0.05, respectively. Concerning operator radiation exposure (µSv), left finger dose: 1,090 (820 to 1,460) versus 635 (300 to 900), p = 0.028; left leg dose 80 (0 to 110) versus 0 (0 to 0), p = 0.027; left eye lens dose: 39 (24 to 69) versus 11 (8 to 20), p <0.0001; and chest dose outside the lead apron: 50 (34 to 88) versus 29 (21 to 50), p <0.003 were significantly lower in the group B than group A. A total of 12 weeks after ST, the total DAP and total air kerma remained stable along with operator exposure except left eye lens dose (µSv): group B: 11 (8 to 20) versus group C: 16 (12 to 27), p = 0.02. In addition, left eye lens dose, left wrist dose, and chest dose outside the lead apron were significantly correlated with total DAP (rs = 0.635, rs = 0.729, and rs = 0, 629, respectively) and total air kerma (rs = 0.488, rs = 0.514, and rs = 0.548, respectively) at 12 weeks. In conclusion, ST for coronary angiography may improve radioprotection learning and should be incorporated into training curricula.

Evolution of arterial stiffness after kidney transplantation.

BACKGROUND: Increased arterial stiffness (AS) is a major determinant of cardiovascular complications in end-stage renal disease (ESRD) patients. Little is known about AS evolution after kidney transplantation. The aim of the study was to characterize the evolution of AS after kidney transplantation in a population of ESRD patients, in comparison to those remaining in dialysis. METHODS: Eighty-eight patients (age between 35 and 65) were recruited from the waiting list for kidney transplantation of the University Hospital of Nancy. Two vascular evaluations were performed at a 1-year interval. During this interval, 39 patients were transplanted and 49 remained in dialysis. RESULTS: At inclusion, median pulse-wave velocity (PWV) was similar in transplanted patients and transplantation-pending patients, respectively, 9.2 (7.9-11.9) and 9.8 (7.7-12.1) m/s. No difference between the two groups was found at the 1-year interval. Median of time after transplantation was 6.3 (3.8-10.1) months. Median of blood pressure (MBP) decreased only in the transplanted patients [99 (93-112) versus 96 (90-101) mmHg, P < 0.01] Multivariate analysis showed that PWV changes depend on changes in MBP and baseline PWV. CONCLUSION: Although no difference in the 1-year PWV evolution was found, the low MBP value in transplanted patients allow to expect a better long-term evolution of AS and a better cardiovascular prognosis after kidney transplantation than in transplantation-pending patients.

Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study.

BACKGROUND: Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. METHODS AND RESULTS: In a substudy of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), which evaluated the effects of the selective aldosterone receptor antagonist eplerenone versus placebo, serum levels of collagen biomarkers were measured in 476 patients with congestive heart failure after acute myocardial infarction complicated with left ventricular systolic dysfunction. The combination of the type I collagen telopeptide and brain natriuretic peptide levels above median at baseline was associated with all-cause mortality and the composite end point of cardiovascular death or heart failure hospitalization, with hazard ratios of 2.49 (P=0.039) and 3.03 (P=0.002), respectively. During follow-up, levels of aminoterminal propeptide of type I and type III procollagen were found to be consistently lower in the eplerenone group and significantly lower beginning at 6 months. CONCLUSIONS: Changes in biomarkers of collagen synthesis and degradation suggest that extracellular matrix remodeling is an active process in patients with congestive heart failure and left ventricular systolic dysfunction after acute myocardial infarction. High type I collagen telopeptide and high brain natriuretic peptide serum levels are associated with the highest event rate. Eplerenone suppresses post-acute myocardial infarction collagen turnover changes.

Predictors of infliximab failure after azathioprine withdrawal in Crohn's disease treated with combination therapy.

OBJECTIVES: Whether all Crohn's disease (CD) patients should maintain long-term azathioprine treatment in combination with infliximab remains controversial. We analyzed the predictive factors of infliximab failure after azathioprine withdrawal. METHODS: This was an observational study from a single referral center. All patients with luminal CD in remission who stopped azathioprine after receiving infliximab in combination with azathioprine for at least 6 months were studied. Cumulative probabilities of infliximab failure-free survival were estimated by the Kaplan-Meier method from the date of azathioprine withdrawal to the date of infliximab failure or last known follow-up. Infliximab failure was defined by: (i) disease flare requiring shortening of the dosing interval or increasing the infliximab dose to 10 mg/kg, or switching to adalimumab; (ii) acute or delayed hypersensitivity reactions leading to infliximab discontinuation; or (iii) CD-related surgery. RESULTS: At last known follow-up, 35 out of 48 (73%) patients were infliximab failure free. The survival probabilities were 85% (+/-5%) at 12 months and 41% (+/-18%) at both 24 and 32 months. Cox proportional-hazards regression identified three predictors of infliximab failure: infliximab-azathioprine exposure duration of < or = 811 days (hazard ratio (HR)=7.46, P=0.01), C-reactive protein > 5 mg/l (HR=4.79, P=0.008), and platelet count > 298 10(9)/l (HR=4.75, P=0.02). CONCLUSIONS: In CD in clinical remission under azathioprine-infliximab combination therapy, azathioprine withdrawal is associated with a high risk of relapse in patients with a duration of combination therapy of < 27 months and/or the presence of biological inflammation.

ECG-triggered 18F-fluorodeoxyglucose positron emission tomography imaging of the rat heart is dramatically enhanced by acipimox.

PURPOSE: 18F-Fluorodeoxyglucose (FDG) imaging, provided by current positron emission tomography (PET) systems dedicated to small animals,might provide a precise functional assessment of the left ventricle (LV) in rats, although conventional metabolic conditioning by hyperinsulinaemic glucose clamping is not well adapted to this setting. This study was aimed at assessing cardiac FDG PET in rats premedicated with acipimox, a potent nicotinic acid derivative yielding comparable image quality to clamping in man. METHODS: Metabolic conditioning was compared in Wistar rats between a conventional oral glucose loading (1.5 mg/kg) and acipimox, which was given at high but well tolerated doses subcutaneously (25 mg/kg) or orally (50 mg/kg). Myocardial to blood (M/B) activity ratio and myocardial signal to noise (S/N) ratio were analysed on gated FDG PET images. RESULTS: The S/N ratio of the gated cardiac images evolved in parallel with the M/B activity ratio and these two ratios were independently enhanced by glucose loading and acipimox. However, these enhancements were: (1) dramatic for acipimox, especially for the high oral dose of 50 mg/kg (from 2.85 +/- 0.57 to 10.73 +/- 0.54 for the M/B ratio of rats with or without glucose loading; p<0.0001) and (2) much more limited for glucose loading (from 6.61 +/- 0.49 to 7.89 +/- 0.41 for the M/B ratio of rats with or without acipimox administration; p=0.049). With the high oral dose of acipimox, the gated cardiac FDG PET images had very high S/N ratios, at least equivalent to those currently documented in man. CONCLUSION: Metabolic conditioning by oral doses of acipimox is highly efficient for experimental studies planned with cardiac FDG PET in rats.

Association study of gene polymorphisms involved in vascular alterations in elderly hypertensives with subjective memory complaints.

BACKGROUND: We have recently shown that vascular abnormalities are associated with cognitive impairment as well as with white matter hyperintensities (WMH) in elderly hypertensive patients presenting with subjective memory complaints (SMC), a population at high risk of developing dementia. The aim of the present study was to identify genetic variants associated with the degree of cognitive impairment and the severity of WMH in the same study population, focusing on genes involved in vascular alterations. METHODS: 50 gene polymorphisms known to be associated with vascular alterations (blood pressure regulation, lipid and homocysteine metabolism, thrombosis and inflammation) were genotyped using a multilocus genotyping assay in 369 elderly treated hypertensive patients >60 years of age and presenting with SMC but no dementia. The patients underwent a combination of neuropsychological tests and brain magnetic resonance imaging with semiquantification of WMH. RESULTS: None of the tested polymorphisms were found to be associated with age- and gender-adjusted memory score, visual capacity, body-mass-index-adjusted verbal fluency score or the age-adjusted WMH Fazekas score. CONCLUSION: Our results suggest that the associations between arterial factors and cognitive decline or WMH are not genetically driven by the genes we investigated, at least at this early stage of cognitive decline.

[Impact of group therapeutic education in the management of adult sleep disorders. Prospective study conducted from September 2007 to March 2008 by a group of general practitioners]. / Impact d'une démarche d'éducation thérapeutique de groupe dans la prise en charge des troubles du sommeil de l'adulte. Etude prospective réalisée de septembre 2007 a mars 2008 par un groupe de médecins généralistes.

UNLABELLED: The prescription of hypnotic drugs in the management of adult insomnia is a public health issue. The implementation of a non-pharmacological, therapeutic approach is a daily problem for primary physicians. OBJECTIVE: This study aimed at assessing the impact of a group therapeutic education approach in the non-medical management of adult insomnia by general practitioners. METHOD: Prospective study conducted from September 2007 to March 2008. Two conferences were held in a two-month period by 5 general practitioners from Laxou, Meurthe-et-Moselle (France). Volunteers were recruited by general practitioners, through local press, posters displayed in pharmacies, leaflet distribution and local radio announcements. A questionnaire was provided at the beginning and the end of the conferences. A phone interview was conducted 1 month and 3 months after the conferences were held, to assess their impact. RESULTS: Seventy-six participants completed the questionnaire during both conferences, and 55 adults were followed-up at 1 and 3 months; 58% (n = 43) were aged over 60, and women represented 65% (n = 48) of the participants; 63% (n = 46) reported insomnia, out of which 89% complained of chronic insomnia (26%, 40% and 34% reported mild insomnia, moderate insomnia and severe insomnia, respectively). At 3 months, 20% of the participants had completed the sleep diary and specifically seen their general practitioner; 56% of the participants taking hypnotic drugs had initiated a dose reduction or a discontinuation of their treatment; 84% of the participants who followed recommendations and initiated cognitive behavioral therapies noted a partial or complete improvement in their sleep disorder. CONCLUSION: Group therapeutic education in the form of cognitive behavioral therapy performed during a conference results in a change in behaviors and a mid-term improvement in sleep quality in participants.

Daily home monitoring of potassium, creatinine, and estimated plasma volume in heart failure post-discharge.

AIMS: Congestive status, serum potassium, and renal function are major determinants of outcomes as well as critical elements for adjusting drug therapy in heart failure (HF) patients. This study aimed at describing the daily variations in estimated plasma volume (ePV, a surrogate of congestion computed from haemoglobin and haematocrit), blood potassium, and estimated glomerular filtration rate during 2 months post-hospitalization for decompensated HF with reduced ejection fraction. METHODS AND RESULTS: The study was conducted in a single tertiary referral centre. Capillary blood samples were drawn by study nurses at home (7-12 am), and haematocrit, blood haemoglobin, creatinine, and potassium were measured using an approved home-based device (ABOTT i-STAT) (ClinicalTrials.gov: NCT01655134). Among the 15 home-monitored patients, two patients died (one suddenly), and one was readmitted for ischaemic acute pulmonary oedema, with a subsequent acute coronary syndrome, and did not have a complete 2-month follow-up. The 5-day-a-week biological home monitoring revealed an ePV >5.5 mL/g Hb, suggestive of undiagnosed residual congestion at discharge in 3 out the 15 patients. It was possible to document a number of episodes of hyperkalaemia (>5: mean ± standard deviation: 2.2 ± 2.2 or 5.5: 1.7 ± 1.6 mmol/L), hypokalaemia (<4: 1.9 ± 2.4 or 3.5: 0.5 ± 1.2 mmol/L), worsening renal function (drop in estimated glomerular filtration rate > 20%: 1.3 ± 1.8 or 30%: 0.7 ± 1.2) and recongestion (ePV rise above 10%: 1.4 ± 1.5, 15%: 2.3 ± 2.4, 5.5 mL/g Hb: 1.8 ± 2.6) episodes indicative of clinically relevant and potentially actionable cardiorenal and electrolytic patterns. CONCLUSIONS: Our findings demonstrate that a 5-day-a-week home monitoring combining haemoglobin/haematocrit, potassium, and creatinine measurements was able to capture a substantial number of clinically relevant cardiorenal and electrolyte events which are frequently overlooked and potentially actionable. Whether acting on these events may help optimizing renin angiotensin aldosterone system inhibitors and diuretic therapy warrants further dedicated testing. The ongoing HERMES HF study (NCT04050904) is assessing the short-term feasibility and safety of such a monitoring strategy, complemented by a decision support system, and generating recommendations based on ESC clinical guidelines in patients discharged after an episode of worsening heart failure with reduced ejection fraction.