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Background The effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline. Methods We did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (Findings We included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and 4788 (1·3%) 85 years and older. The hazard ratios for the risk of major cardiovascular events per 5 mm Hg reduction in systolic blood pressure for each age group were 0·82 (95% CI 0·76–0·88) in individuals younger than 55 years, 0·91 (0·88–0·95) in those aged 55–64 years, 0·91 (0·88–0·95) in those aged 65–74 years, 0·91 (0·87–0·96) in those aged 75–84 years, and 0·99 (0·87–1·12) in those aged 85 years and older (adjusted pinteraction=0·050). Similar patterns of proportional risk reductions were observed for a 3 mm Hg reduction in diastolic blood pressure. Absolute risk reductions for major cardiovascular events varied by age and were larger in older groups (adjusted pinteraction=0·024). We did not find evidence for any clinically meaningful heterogeneity of relative treatment effects across different baseline blood pressure categories in any age group. Interpretation Pharmacological blood pressure reduction is effective into old age, with no evidence that relative risk reductions for prevention of major cardiovascular events vary by systolic or diastolic blood pressure levels at randomisation, down to less than 120/70 mm Hg. Pharmacological blood pressure reduction should, therefore, be considered an important treatment option regardless of age, with the removal of age-related blood-pressure thresholds from international guidelines. Funding British Heart Foundation, National Institute of Health Research Oxford Biomedical Research Centre, Oxford Martin School.

Mean Gradient (MG) elevation can be detected immediately after transcatheter aortic valve implantation (TAVI) or secondarily during follow-up. Comparisons and interactions between these two parameters and their impact on outcomes have not previously been investigated. This study aimed to identify incidence, influence on prognosis, and parameters associated with immediate high post-procedural mean transvalvular gradient (PPMG) and delayed mean gradient increase (6 to 12 months after TAVI, DMGI) in the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry. The registry includes all consecutive symptomatic patients with severe aortic stenosis who have undergone TAVI. Three groups were analyzed: (1) PPMG &lt, 20 mmHg without DMGI &gt, 10 mmHg (control), (2) PPMG &lt, 20 mmHg with DMGI &gt, 10 mmHg (Group 1), and (3) PPMG ≥ 20 mmHg (Group 2). From January 2010 to January 2012, 4201 consecutive patients were prospectively enrolled in the registry. Controls comprised 2078 patients. In Group 1(n = 131 patients), DMGI exceeded 10 mmHg in 5.6%, and was not associated with greater 4-years mortality than in controls (32.6% vs. 40.1%, p = 0.27). In Group 2 (n = 144 patients), PPMG was at least 20 mmHg in 6.1% and was associated with higher 4-year mortality (48.7% versus 40.1%, p = 0.005). A total of two-thirds of the patients with PPMG ≥ 20 mmHg had MG &lt, 20 mmHg at 1 year, with mortality similar to the controls (39.2% vs. 40.1%, p = 0.73). Patients with PPMG &gt, 20 mmHg 1 year post-TAVI had higher 4-years mortality than the general population of the registry, unlike patients with MG normalization.

Background The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure. Methods We did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from

BACKGROUND: Coronary artery disease (CAD) is common in patients undergoing transcatheter aortic valve replacement (TAVR). However, the impact of CAD distribution before TAVR on short‐ and long‐term prognosis remains unclear. HYPOTHESIS: We hypothesized that the long‐term clinical impact differs according to CAD distribution in patients undergoing TAVR using the FRench Aortic National CoreValve and Edwards (FRANCE‐2) registry. METHODS: FRANCE‐2 is a national French registry including all consecutive TAVR performed between 2010 and 2012 in 34 centers. Three‐year mortality was assessed in relation to CAD status. CAD was defined as at least 1 coronary stenosis >50%. RESULTS: A total of 4201 patients were enrolled in the registry. For the present analysis, we excluded patients with a history of coronary artery bypass. CAD was reported in 1252 patients (30%). Half of the patients presented with coronary multivessel disease. CAD extent was associated with an increase in cardiovascular risk profile and in logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (from 19.3% ± 12.8% to 21.9% ± 13.5%, P < 0.001). Mortality at 30 days and 3 years was 9% and 44%, respectively, in the overall population. In multivariate analyses, neither the presence nor the extent of CAD was associated with mortality at 3 years (presence of CAD, hazard ratio [HR]: 0.90; 95% confidence interval [CI]: 0.78‐1.07). A significant lesion of the left anterior descending (LAD) was associated with higher 3‐year mortality (HR: 1.42; 95% CI: 1.10‐1.87). CONCLUSIONS: CAD is not associated with decreased short‐ and long‐term survival in patients undergoing TAVR. The potential deleterious effect of LAD disease on long‐term survival and the need for revascularization before or at the time of TAVR should be validated in a randomized control trial.

Analysis of the causes, outcomes, and mortality of patients with severe symptomatic aortic stenosis requiring the implantation of 2 valves during transcatheter aortic valve implantation was conducted from the French Aortic National CoreValve and Edwards 2 (FRANCE2) registry. Pre- and postprocedural data from 3,919 patients from January 2010 to December 2011 (CoreValve or Edwards) were collated and analyzed. Characteristics of patients requiring immediate second valve procedures were compared with those of the other patients. The 72 patients (1.8%) who underwent implantation of a second valve were studied. Indications were device malpositioning (72%) and embolization (28%). Clinical and echocardiographic characteristics of patients receiving 2 valves were comparable with those of the other patients. The 2-year survival rate was 51.7% for patients with 2 valves as opposed to 62.3% for those with 1 valve (p0.001). The need for a second valve was an independent predictor of all-cause (hazard ratio 2.32, 95% confidence interval 1.50 to 3.60, p0.001) and cardiovascular (hazard ratio 2.64, 95% confidence interval 1.35 to 5.15, p0.001) mortality at 2 years. During follow-up, clinical and echocardiographic data remained similar between the 2 groups. In conclusion, in the FRANCE2 study, the main causes for second valve implantation during the same procedure were malpositioning and embolization. Although the procedure was feasible, it was accompanied by excess mortality. Valve hemodynamic status was preserved during the course of follow-up.

Aim DIALOG assessed the prevalence and predictors of hypoglycaemia in patients with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) in a real-life setting. Methods In this observational study, insulin-treated patients ( n =3048) completed prospective daily questionnaires reporting the frequency and consequences of severe/confirmed non-severe hypoglycaemia over 30 days. Patients ( n =3743) also retrospectively reported severe hypoglycaemia over the preceding year. Results In this prospective survey, 85.3% and 43.6% of patients with T1DM and T2DM, respectively, reported experiencing at least one confirmed hypoglycaemic event over 30 days, while 13.4% and 6.4%, respectively, reported at least one severe event. Hypoglycaemia frequency increased with longer duration of diabetes and insulin therapy. Strongly predictive factors for hypoglycaemia were previous hypoglycaemia, >2 injections/day, BMI 2 and duration of insulin therapy>10 years. HbA 1c level was not predictive of hypoglycaemia in either T1DM or T2DM. The confirmed hypoglycaemia rate was increased in the lowest compared with the highest tertile of HbA 1c in T1DM, but not T2DM. At the time of enrolment, physicians reported severe hypoglycaemia in 23.6% and 11.9% of T1DM and T2DM patients, respectively, during the preceding year; the retrospective survey yielded frequencies of 31.5% and 21.7%, respectively. Also, severe hypoglycaemia led to medical complications in 10.7% and 7.8% of events in T1DM and T2DM patients, respectively, over 30 days. Conclusion Using a unique combined prospective and retrospective approach, the DIALOG study found a relatively high frequency of hypoglycaemia among insulin-treated patients. These findings emphasize the importance of a patient-centred approach for managing diabetes in which hypoglycaemia risk evaluation is critical. Trial registration ClinicalTrials.gov: NCT01628341.

Summary Background Some patients who are at high surgical risk because of multiple co-morbidities undergo balloon aortic valvuloplasty (BAV) as a bridge therapy towards transcatheter aortic-valve implantation (TAVI). Aim The aim of this study was to compare the clinical course of patients with or without previous BAV who underwent TAVI and were included in the FRANCE 2 registry. Methods From January 2010 to December 2011, 3953 patients underwent TAVI. Survival analysis was done by multivariable regression and propensity-score analysis to adjust for confounders. Results Patients in the previous BAV group ( n = 664, 16.8%) were older than patients in the primary TAVI group. The logistic EuroSCORE I and the rates of co-morbidities and symptoms were higher in the previous BAV group. Procedural success was similar in both groups, as was postprocedural aortic regurgitation grade ≥ 2/4. The 1-month mortality rates from all causes were 12.5 and 8.7%, respectively, in the previous BAV and primary TAVI groups ( P = 0.001). The 1-month to 1-year mortality rates were similar in both groups. Previous BAV was not an independent predictor of 1-month mortality (hazard ratio 1.44, 95% confidence interval 0.90–2.34; P = 0.14) or 1-month to 1-year mortality. Conclusions Crude 1-month mortality was higher in patients with previous BAV. Nevertheless, precarious preoperative status, but not previous BAV, was associated with mortality, and is the only marker that should be considered as detrimental at the time of preTAVI reassessment.

Objectives The aim of this study was to analyze the incidence, impact, and predictors of cerebrovascular events (CVEs) in patients undergoing transcatheter aortic valve replacement (TAVR). Background Several issues remain unresolved post-TAVR, including CVEs. Methods The FRANCE-2 (French Aortic Nation CoreValve and Edwards-2) registry prospectively included all patients who underwent TAVR in France and Monaco from January 2010 to October 2011. A total of 3,191 patients were analyzed. Six-month follow-up data were obtained. Events were adjudicated according to Valve Academic Research Consortium (VARC)-1 definition. Results Of the cohort, 3.98% experienced a CVE: 55% were major strokes, 14.5% minor strokes, and 30.5% transient ischemic attacks. The mean delay for CVE occurrence was 2 days (interquartile range: 0 to 7 days) with 48.5% of CVEs occurring within 2 days. There was no statistically significant difference in CVE rate with regard to the type of valve (p = 0.899) and the access route (p = 0.128). Patients with a CVE more frequently had new-onset paroxysmal atrial fibrillation (13.6% vs. 7.6%; p = 0.015). During follow-up, the unadjusted mortality rate was higher in patients with a CVE (26% vs. 16.5%; p = 0.002). By multivariate analysis, only advanced age (odds ratio: 1.05; 95% confidence interval: 1.02 to 1.08; p = 0.02) and having 2 valves implanted (odds ratio: 3.13; 95 confidence interval: 1.40 to 7.05; p = 0.006) were associated with a significant risk of CVEs. Conclusions CVEs occur frequently after TAVR and are associated with an increased mortality rate. No difference exists in the CVE rate when exploring the type of valve or the access route. Advanced age and multiple valves implanted during the same procedure are predictors of CVE.

The purposes of the present study were to determine the impact of chronic obstructive pulmonary disease (COPD) on Valve Academic Research Consortium-defined outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). A total of 3,933 consecutive patients underwent TAVI from January 2010 to December 2011 in 34 centers and were included in the French national TAVI registry "FRANCE 2"; 895 (22.7%) had concomitant COPD, 3,038 (77.3%) did not. There were no significant differences in procedural characteristics or 30-day Valve Academic Research Consortium-defined outcomes between those with and without COPD. Multivariate regression analysis showed COPD to be an independent predictor of 1-year mortality and combined efficacy end point after adjustment for concomitant co-morbidities (hazard ratio 1.19, 95% confidence interval 1.005 to 1.41, p = 0.03 and hazard ratio 1.52, 95% confidence interval 1.29 to 1.79, p 0.001, respectively). The higher mortality rate at 1 year in patients with COPD was related to cardiovascular deaths (COPD 10.0% vs non-COPD 6.2%, p = 0.008). Subgroup analysis found that the effect of COPD on 1-year mortality rate was constant across different subgroups, especially the type of approach and the type of anesthesia subgroups. In conclusion, concomitant COPD in patients referred for TAVI characterizes a high-risk population. The excess in mortality is largely determined by a higher rate of cardiovascular deaths and exists regardless of the type of procedure performed and its results.

Introduction Regular monitoring of the international normalized ratio (INR) is crucial for dose adjustment of vitamin K antagonists (VKA) to maximize time in therapeutic range (TTR). We compared the use of a mobile electronic assistant INRPlus which proposes patient-specific fluindione doses, to standard fluindione management in a cluster randomized controlled study. Patients and Methods Twenty clusters of six general practitioners were randomized to adjust fluindione doses in VKA-treated patients either using INRPlus or according to routine practice. TTR was measured over 6 months, along with time spent above or below the recommended INR range, frequency of measurements and related complications. Results Of the 595 included patients, 551 were assessable (259 INRPlus, 292 control) and had a mean of 1.6 INR measurements/month. TTR was not significantly different between the two groups, 72.7% [Q1: 58.1%; Q3: 90%] in INRPlus patients and 71.2% [Q1: 54.8%; Q3: 88.2%] in control patients (p = 0.445). At least 60% time within reference ranges was reported in 73.4% of INRPlus patients and 67.1% of control patients (relative risk 1.09, 95%CI 0.98-1.22, p = 0.115). No significant differences were reported between the two groups for time outside reference ranges, frequency of measurements or complications. Eighty-two percent (82%) of patients complying with INRPlus-proposed doses spent more than 60% of TTR versus 66.9% of non-compliant patients and 67.1% of reference patients. Conclusions In this trial, the use of the INRPlus electronic assistant resulted in a non-significant improvement in TTR that may be due to a higher than expected TTR in the control group.

Objective Decision making for intervention in symptomatic aortic stenosis should balance the risks of surgery and of transcatheter aortic valve implantation (TAVI). We identified the factors associated with early mortality after TAVI and aimed to develop and validate a simple risk score. Methods A population of 3833 consecutive patients was randomly split into two cohorts comprising 2552 and 1281 patients, used respectively to develop and validate a scoring system predicting 30-day or in-hospital mortality. Results TAVI was performed using the Edwards Sapien prosthesis in 2551 (66.8%) patients and the Medtronic Corevalve in 1270 (33.2%). Approach was transfemoral in 2801 (73.4%) patients, transapical in 678 (17.8%), subclavian in 219 (5.7%) and other in 117 (3.1%). Early mortality was 10.0% (382 patients). A multivariate logistic model identified the following predictive factors of early mortality: age ≥90 years, body mass index 2 , New York Heart Association class IV, pulmonary hypertension, critical haemodynamic state, ≥2 pulmonary oedemas during the last year, respiratory insufficiency, dialysis and transapical or other (transaortic and transcarotid) approaches. A 21-point predictive score was derived. C-index was 0.67 for the score in the development cohort and 0.59 in the validation cohort. There was a good concordance between predicted and observed 30-day mortality rates in the development and validation cohorts. Conclusions Early mortality after TAVI is mainly related to age, the severity of symptoms, comorbidities and transapical approach. A simple score can be used to predict early mortality after TAVI. The moderate discrimination is however a limitation for the accurate identification of high-risk patients.

Suite a la demande de la Direction Generale de la Sante, une etude a ete mise en place afin d’evaluer les modalites d’utilisation de l’insuline glargine chez des patients diabetiques en conditions de pratique reelle en France, de decrire le niveau de controle glycemique obtenu et l’incidence des hypoglycemies observees. Il s’agissait d’une etude prospective, observationnelle, multicentrique, nationale de suivi sur un an d’une cohorte de patients diabetiques de type 1 (DT1) et de type 2 (DT2) traites depuis au moins un mois avec de l’insuline glargine et suivis pendant un an par des medecins generalistes, diabetologues et pediatres. L’analyse porte sur 1 707 patients, dont 609 patients DT1 et 1 097 patients DT2 (et un patient avec un diabete non determine). L’âge moyen des patients etait de 42,0 ± 19,4 ans pour les DT1 et de 67,0 ± 11,9 ans pour les DT2, 642 (58,5 %) patients etaient âges de 65 ans et plus et 325 (29,6 %) de 75 ans et plus. L’anciennete moyenne du diabete etait respectivement de 15,8 ± 12,5 et 14,0 ± 8,8 ans. Parmi les patients DT2, 57 % etaient naifs d’insuline avant l’initiation de l’insuline glargine (DT2-IN) et 43 % etaient deja traites par une insuline (DT2-IT). La raison de l’initiation de l’insuline glargine etait principalement un mauvais controle de la glycemie. L’utilisation de l’insuline glargine a conduit a une augmentation importante de l’utilisation du schema therapeutique basal-bolus chez les DT1 et DT2-IT, respectivement de 32 % a 84,7 % et de 8,4 % a 38,8 % et a une diminution du nombre d’antidiabetiques oraux associes chez les DT2-IN, ainsi que chez les patients âges de plus de 65 ans. La dose moyenne d’insuline glargine a l’inclusion etait de 24,2 U/j chez les DT1, de 31,6 U/j chez les DT2-IT et de 23,6 U/j chez les DT2-IN. Au cours du suivi, cette dose est restee stable pour les DT1, et a augmente chez les DT2 (atteignant 35 U/j pour les DT2-IT et 29,7 U/j pour les DT2-IN) La proportion de patients atteignant les objectifs glycemiques (HbA1c En conclusion, les resultats de cette etude en vie reelle ont montre un profil d’utilisation de l’insuline glargine en France conforme au bon usage et aux recommandations de prise en charge du patient diabetique conjointes de la HAS et de l’AFSSAPS en vigueur. Le controle glycemique, initialement ameliore suite a l’instauration de l’insuline glargine, s’est maintenu pendant le suivi a 12 mois. Une augmentation du nombre de patients atteignant l’objectif d’HbA1c (

We updated the 2002 Antiplatelet Trialists' Collaboration meta-analysis of antiplatelet therapy to assess the effects of aspirin alone in the secondary prevention of different types of thrombotic arterial disease. Results of randomized, placebo-controlled trials of aspirin in patients with confirmed cardiovascular disease were abstracted and synthesized by the Mantel-Haenszel method. We defined three cardiovascular disease groups according to the qualifying disease at entry: coronary artery disease (CAD), cerebrovascular disease (CRVD), and peripheral arterial disease (PAD). Results are given as odds ratios (OR) and 95% confidence intervals (95% CI). Compared with placebo, aspirin decreased significantly the risk of all-cause death in CAD and CRVD (OR = 0.80, 95% CI 0.75-0.86 and 0.91, 95% CI 0.85-0.98, respectively), and of vascular events in CAD, CRVD, and PAD (OR = 0.71, 95% CI 0.67-0.76, 0.87, 95% CI 0.82-0.93, and 0.50, 95% CI 0.29-0.88, respectively). The risk of non-fatal stroke was decreased in the CAD, CRVD, and PAD (OR = 0.64, 95% CI 0.50-0.83, 0.81, 95% CI 0.74-0.89, and 0.26, 95% CI 0.07-0.94, respectively). The risk of non-fatal myocardial infarction was decreased significantly in the CAD and CRVD (OR = 0.59, 95% CI 0.53-0.67, and 0.63, 95% CI 0.48-0.84, respectively), but not in the PAD (OR = 0.43, 95% CI 0.15-1.25). Aspirin nearly doubled the risk of major bleeds (OR = 1.87, 95% CI 1.51-2.32 for all clinical conditions). This meta-analysis confirms that aspirin decreases the risk of thrombotic events in patients with confirmed disease of the coronary, cerebrovascular, or peripheral artery beds.

International audience; Previous coronary artery bypass grafting (CABG) increases operative risk in conventional valve replacement. Transcatheter aortic valve implantation (TAVI) has been shown to be successful in high-risk patient subgroups. The present study compared outcome and overall survival in patients who underwent TAVI with and without history of CABG. From January 2010 to December 2011, 683 of the 3,761 patients selected for TAVI in 34 French centers (18%) had a history of CABG. Outcomes (mortality and complications) were collected prospectively according to the Valve Academic Research Consortium (VARC) criteria. Patients with previous CABG were younger, with higher rates of diabetes and vascular disease and higher logistic European System for Cardiac Operative Risk Evaluation (29.8 ± 16.4 vs 20.1 ± 13.0, p

International audience; OBJECTIVES: The relationship between anemia, renal insufficiency, and the outcomes of TAVI patients has not been thoroughly studied. We aimed to evaluate the influence of pre- and post-procedural anemia on the incidence of renal insufficiency, especially AKI, and on the outcomes of TAVI. METHODS: Data from the French national TAVI registry were collected in 3,472 patients who underwent TAVI between January 2010 and December 2012. Of these 2,137 were in the no/mild anemia group, 748 were in the moderate anemia group, and 587 were in the severe anemia group before TAVI. Furthermore, we divided the 3,472 patients into three groups according to post-procedural anemia, measured as post-procedural hemoglobin (Hb) drop: \textless2 g/dl (n=1,633, group 1), 2 to \textless4 g/dl (n=1,458, group 2), and \textgreater4 g/dl (n = 381, group 3). Procedure and outcome variables were compared. RESULTS: Increased severity of anemia before TAVI was associated with significantly different rates of 1-year mortality (15%, 19%, and 24%, P\textless0.01), with similar differences in the incidence of AKI (5%, 8%, and 10%, P\textless0.01). Increased severity of Hb drop was associated with significantly different rates of 1-year mortality (16%, 18%, and 23%, P\textless0.01), and with similar differences in the incidence of AKI (6%, 7%, and 10%, P=0.04). Both pre- and post-procedural anemia were predictors of the incidence of AKI (OR 1.82, P\textless0.01; OR 1.82, P\textless0.01, respectively) and 1-year mortality (HR 1.44, P\textless0.01; HR 1.50, P\textless0.01, respectively). CONCLUSIONS: Both pre- and post-procedural anemia were significantly associated AKI and 1-year mortality

Aims The aim of this study was to assess the influence of chronic kidney disease (CKD) classification on clinical outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results Data of 2,929 consecutive patients undergoing TAVI in the FRANCE 2 registry were analysed. Patients were divided into five groups: CKD 1+2, 3a, 3b, 4, and 5. Both 30-day and one-year mortality rates were significantly increased and positively correlated with CKD severity in all groups. After adjusting for significant influential confounders in a Cox regression multivariate model, CKD 4 and 5 were associated with increased risk of both 30-day mortality and one-year mortality when compared with CKD 1+2 as the reference. This higher mortality was predominantly driven by renal failure and infection in patients with CKD 4 and 5, respectively. Procedural success rate in CKD 5 was significantly lower than that in other groups. All CKD patients trended towards a higher incidence of acute kidney injury (AKI), in parallel with the degree of CKD severity. Conclusions Classification of CKD stages before TAVI allows risk stratification for 30-day and one-year clinical outcomes. CKD 3b, 4 and 5 correlate with poor outcome and are considered a significant risk for TAVI.

We thank Drs Iqbal and Serruys for their interesting comments on our study.1 Transcatheter aortic valve replacement is a very good alternative to conventional surgical replacement in patients with aortic stenosis at increased risk for surgery.2,3 As efficient as it is, transcatheter aortic valve replacement has important limitations, including postprocedural aortic regurgitation (AR). Our study was designed to (1) describe the rate of postprocedural AR evaluated at discharge in a large series of consecutive patients treated with balloon-expandable (BE) and self-expandable devices, (2) analyze the predictors of postprocedural ARs in the overall population for each device, and (3) analyze the impact of postprocedural ARs on clinical outcome. The results of our study1 and others2 demonstrate clearly that postprocedural AR≥moderate as evaluated by echocardiography at discharge is frequent (15%) and is an independent predictor of long-term mortality. Our study demonstrates also that the clinical significance of a postprocedural AR≥moderate is …

Preventing coronary in-stent restenosis is a major challenge for physicians and industry. To assess new stent technologies, a comparative paired iliac artery model in rabbits is proposed. One tubular stent was implanted in each external iliac artery in 12 rabbits (i.e., 24 stents). An artery overdilatation level of 20% was strictly observed. Restenosis was examined at 30 days by angiography, intravascular ultrasound (IVUS) examination, and histomorphometry. On quantitative angiography, the mean loss of angiographic diameter was 9.8 ± 4.4% in the right as compared to 9.3 ± 55% in the left artery (p = 0.75). On IVUS, the volume of intrastent neointimal proliferation was 26.6 ± 4.9 mm3 in the right and 25.8 ± 3.5 mm3 in the left artery (p = 0.58). In histomorphometry, the neointimal proliferation area was 0.78 ± 17 mm2 in the right and 0.76 ± 0.17 mm2 in the left artery (p = 0.87). Intrastent neointimal proliferation was comparable between the left and right arteries of all rabbits. The model has three main advantages: (1) arterial dilatation and thus arterial wall aggression are controlled, (2) pairing makes each animal its own control subject, and (3) the statistical power for comparative testing is maximized. The model enables the effect of a new drug-delivery device to be assessed. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 303–310, 2004

The efficacy and safety of lipid-lowering agents in elderly individuals have not been extensively assessed. This population generally takes more drugs concurrently than middle-aged patients, and are therefore at higher risk of drug-drug interactions. This large-scale, randomized, double-blind, placebo-controlled study investigated the efficacy and safety of extended-release (XL) fluvastatin 80 mg once daily for up to 1 year in elderly patients with primary hypercholesterolemia. A total of 1229 patients (mean age, 75.5 years) were randomized. After 2 months of treatment, fluvastatin XL 80 mg significantly decreased plasma lipid levels from baseline compared with placebo; fluvastatin reduced total cholesterol by 25% compared with a decrease of 2.5% in the placebo group, low-density lipoprotein cholesterol was -33% vs. -2.5%, respectively, and triglycerides were -13.3% vs. 2.9%, respectively (p

OBJECTIVE—The DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study allowed investigators to analyze factors leading to the development of congestive heart failure (CHF) in type 2 diabetic patients with abnormal urinary albumin concentration. RESEARCH DESIGN AND METHODS—Type 2 diabetic subjects of both sexes aged ≥50 years who had a urinary albumin concentration ≥20 mg/l were randomly allocated to 1.25 mg/day ramipril or placebo in addition to their usual treatment and treated for 3–6 years in a double-blind fashion. Major outcomes including hospitalization for CHF were recorded during the follow-up. RESULTS—Of the 4,912 included patients, 187 developed CHF during the study. There was no significant difference in the incidence of CHF between the two treatment groups. Using a multivariate analysis, independent risk factors for the occurrence of CHF were age, history of cardiovascular disease, baseline urinary albumin concentration, baseline HbA1c, and smoking habits. A total of 68 of the 187 patients (36.4%) died during the 12 ± 11-month period after the first hospitalization for CHF, whereas the annual mortality rate of the population who did not develop CHF was 3.2%. CONCLUSIONS—Presence of atherosclerotic disease, baseline urinary albumin concentration, and HbA1c level were indicators for further development of CHF. Occurrence of CHF is a major prognostic turn in a diabetic patient’s life.

AIMS To assess the relationship between a low preprocedural (

Background and Purpose— We aimed at comparing the long-term benefit–risk balance of carotid stenting versus endarterectomy for symptomatic carotid stenosis. Methods— Long-term follow-up study of patients included in Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S), a randomized, controlled trial of carotid stenting versus endarterectomy in 527 patients with recently symptomatic severe carotid stenosis, conducted in 30 centers in France. The main end point was a composite of any ipsilateral stroke after randomization or any procedural stroke or death. Results— During a median follow-up of 7.1 years (interquartile range, 5.1–8.8 years; maximum 12.4 years), the primary end point occurred in 30 patients in the stenting group compared with 18 patients in the endarterectomy group. Cumulative probabilities of this outcome were 11.0% (95% confidence interval, 7.9–15.2) versus 6.3% (4.0–9.8) in the endarterectomy group at the 5-year follow-up (hazard ratio, 1.85; 1.00–3.40; P =0.04) and 11.5% (8.2–15.9) versus 7.6% (4.9–11.8; hazard ratio, 1.70; 0.95–3.06; P =0.07) at the 10-year follow-up. No difference was observed between treatment groups in the rates of ipsilateral stroke beyond the procedural period, severe carotid restenosis (≥70%) or occlusion, death, myocardial infarction, and revascularization procedures. Conclusions— The long-term benefit–risk balance of carotid stenting versus endarterectomy for symptomatic carotid stenosis favored endarterectomy, a difference driven by a lower risk of procedural stroke after endarterectomy. Both techniques were associated with low and similar long-term risks of recurrent ipsilateral stroke beyond the procedural period. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00190398.

The "obesity paradox" that patients with high body mass index (BMI) have good prognoses remains controversial. This study aimed to assess the impact of BMI on clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI). Data from the French national TAVI registry were collected for 3,072 patients who underwent TAVI from January 2010 to October 2011. The patients were categorized into 4 groups according to BMI (kg/m(2)): underweight (18.5 kg/m(2)), normal weight (18.5 to 25 kg/m(2)), overweight (25 to 30 kg/m(2)), and obese (30 kg/m(2)). Thereafter, clinical outcomes were compared among the 4 groups. The BMI distribution was 3.1% (n = 95), 44.1% (n = 1,355), 34.2% (n = 1,050), and 18.6% (n = 572). Although the 4 groups greatly differed in baseline clinical background, they had similar procedural success rates (95.8%, 97.1%, 97.3%, and 95.6%, p = 0.23). Major vascular complication was significantly associated with the underweight patients after adjusting for the other potential confounders (odds ratio 2.33, 95% confidence interval 1.17 to 4.46, p = 0.016). The cumulative postoperative survival rates were increasing across the 4 groups at 30 days (83.2%, 88.9%, 91.6%, and 93.0%, p = 0.003) and 1 year (67.9%, 73.6%, 77.4%, and 80.3%, p = 0.006). In a multivariate Cox regression analysis, the overweight and obese patients were independently associated with superior cumulative survival rate at 1 year (hazard ratios 0.74 and 0.71, 95% confidence intervals 0.57 to 0.97 and 0.59 to 0.87, p = 0.050 and 0.029, respectively). In conclusion, major morbidity and 1-year mortality were less in overweight and obese patients than those classified as normal weight even in a TAVI cohort.

Abstract The objective of this trial was to assess the effects of 6-month daily treatment with two doses of ramipril on left ventricular mass and the dependence of this on blood pressure changes in hypertensive patients with left ventricular hypertrophy. After a selection phase of 4 to 6 weeks with patients under antihypertensive therapy with 20 mg furosemide daily, 115 patients with either controlled or uncontrolled hypertension and left ventricular hypertrophy were randomized in a double-blind manner to receive either placebo (n=40), 1.25 mg (low dose, n=38), or 5 mg (regular dose, n=37) ramipril daily for 6 months. Treatment with furosemide was continued unchanged during this phase. The main outcome measured was left ventricular hypertrophy regression as assessed from central blind reading of echocardiograms recorded at randomization and after 6 months. No significant differences were observed for changes in casual or ambulatory blood pressure between the three groups. Left ventricular mass index was found to be significantly reduced in patients receiving 5 mg ramipril compared with those receiving placebo (−10.8±3.7 versus +4.1±4.0 g/m 2 , P =.008); in patients receiving 1.25 mg ramipril, the difference was close to borderline significance compared with placebo (−7.0±4.3 g/m 2 , P =.06). Similar results were observed for changes in left ventricular mass (−20.3±6.6 and −13.0±7.8 g in the 5- and 1.25-mg ramipril groups, respectively, versus +9.1±7.2 g in the placebo group; P =.004 and .04, respectively). In a multiple regression model testing 10 potential explicative variables, we found that this reduction was correlated with treatment, both 1.25 and 5.0 mg ramipril ( P =.03 and .01, respectively), and with the baseline value of the left ventricular mass index ( P =.005). Changes in ambulatory or casual systolic and diastolic blood pressures were not predictive of changes in left ventricular mass ( P =.15 and .16, respectively). Ramipril at 1.25 and 5 mg daily for 6 months can induce left ventricular hypertrophy regression, independent of changes in blood pressure, in patients under furosemide (20 mg/d) antihypertensive therapy. The implications of this regression for cardiovascular morbidity and mortality in hypertensive patients should now be assessed.

Existing cardiovascular risk prediction equations perform non-optimally in different populations with diabetes. Thus, there is a continuing need to develop new equations that will reliably estimate cardiovascular disease (CVD) risk and offer flexibility for adaptation in various settings. This report presents a contemporary model for predicting cardiovascular risk in people with type 2 diabetes mellitus.A 4.5-year follow-up of the Action in Diabetes and Vascular disease: preterax and diamicron-MR controlled evaluation (ADVANCE) cohort was used to estimate coefficients for significant predictors of CVD using Cox models. Similar Cox models were used to fit the 4-year risk of CVD in 7168 participants without previous CVD. The model's applicability was tested on the same sample and another dataset.A total of 473 major cardiovascular events were recorded during follow-up. Age at diagnosis, known duration of diabetes, sex, pulse pressure, treated hypertension, atrial fibrillation, retinopathy, HbA1c, urinary albumin/creatinine ratio and non-HDL cholesterol at baseline were significant predictors of cardiovascular events. The model developed using these predictors displayed an acceptable discrimination (c-statistic: 0.70) and good calibration during internal validation. The external applicability of the model was tested on an independent cohort of individuals with type 2 diabetes, where similar discrimination was demonstrated (c-statistic: 0.69).Major cardiovascular events in contemporary populations with type 2 diabetes can be predicted on the basis of routinely measured clinical and biological variables. The model presented here can be used to quantify risk and guide the intensity of treatment in people with diabetes.

Background Most guidelines recommend a systematic screening of asymptomatic high risk patients with diabetes for silent ischemia, but the clinical benefit of this strategy has not been demonstrated compared with the simple control of cardiovascular risk factors. We sought to determine whether referring asymptomatic diabetic patients for screening of silent ischemia decreases the risk of cardiovascular events compared with usual care. Methods DYNAMIT was a prospective, randomized, open, blinded end-point multicenter trial run between 2000 and 2005, with a 3.5 year mean follow-up in ambulatory care in 45 French hospitals. The study included 631 male and female with diabetes aged 63.9 ± 5.1 years, with no evidence of coronary artery disease and at least 2 additional cardiovascular risk factors, receiving appropriate medical treatment. The patients were randomized centrally to either screening for silent ischemia using a bicycle exercise test or Dipyridamole Single Photon Emission Computed Tomography (N = 316), or follow-up without screening (N = 315). The main study end point was time to death from all causes, non-fatal myocardial infarction, non-fatal stroke, or heart failure requiring hospitalization or emergency service intervention. The results of a meta-analysis of DYNAMIT and DIAD, a similar study, are also presented. Results The study was discontinued prematurely because of difficulties in recruitment and a lower-than expected event rate. Follow-up was complete for 98.9% patients regarding mortality and for 97.5% regarding the main study end point. Silent ischemia detection procedure was positive or uncertain in 68 (21.5%) patients of the screening group. There was no significant difference between the screening and the usual care group for the main outcome (hazard ratio = 1.00 95%CI 0.59 to 1.71). The meta-analysis of these and DIAD results gave similar results, with narrower confidence intervals for each endpoint. Conclusions These results suggest that the systematic detection of silent ischemia in high-risk asymptomatic patients with diabetes is unlikely to provide any major benefit on hard outcomes in patients whose cardiovascular risk is controlled by an optimal medical treatment. Trial registration ClinicalTrials.gov: NCT00627783

Correction of anemia in type 2 diabetes (T2DM) patients with chronic kidney disease stages 3-4 may slow the decline of kidney function but may increase cardiovascular risk through higher hematocrit. The NEPHRODIAB2 study was designed to assess efficacy and safety of complete hemoglobin (Hb) normalization in these patients.We randomly assigned 89 T2DM patients with an estimated glomerular filtration rate (eGFR; abbreviated 175 Modification of Diet in Renal Disease formula) of 25 to 60 ml/min per 1.73 m(2) and moderate anemia (Hb, 100-129 g/l) to a target Hb value in subnormal range (110-129g/l, group 1, n=43) or normal range (130-149 g/l, group 2, n=46). The primary end point was eGFR decline after 2 years of follow-up. Secondary end points included iron and erythropoietin dosage, quality of life (Medical Outcomes Study 36-item Short-Form Health Survey scores) and adverse events.Six months after randomization, the mean Hb levels were120 g/l in group 1 and130 g/l in group 2 (P.05 at 6, 12, 18 and 24 months). Blood pressure, 24-h proteinuria and HbA1c did not differ during follow-up (P.05). Two-year declines in eGFR were -8.7±12.2 in group 1 and -5.1±7.8 ml/min per 1.73 m(2) in group 2 (P=.29). Mean weekly use of erythropoietin was 7.8±11.6 μg in group 1 and 30.1±33.6 μg in group 2 (P.0001). There was no significant difference regarding Medical Outcomes Study 36-item Short-Form Health Survey score change or adverse event occurrence.In this trial, normalization of Hb level in T2DM patients with chronic kidney disease was safe but did not significantly slow renal function decline and increased treatment cost due to erythropoietin use.

Introduction L’evaluation de la peur de l’hypoglycemie chez le diabetique est importante, mais peu d’outils sont disponibles en pratique clinique. Le questionnaire valide HFS-II (Hypoglycemia Fear Survey-II) mesure la crainte du risque de survenue d’hypoglycemies en evaluant les consequences de l’hypoglycemie et le comportement du patient en retour, ainsi que le degre d’inquietude liee a l’hypoglycemie. L’objectif de cette analyse est d’evaluer les associations cliniques d’un score eleve (>+ 1DS) sur une HbA1c ≥ 7 % et/ou sur la survenue d’une hypoglycemie severe sur trente jours. Patients et methodes Les donnees de 1927 diabetiques francais (1 008 DT1, 919 DT2 insulino-traites) ayant complete le questionnaire HFS-II dans l’etude observationnelle DIALOG ont ete etudiees. Les facteurs correles ont ete analyses avec un modele de regression multivarie. Resultats Les facteurs correles a une valeur de HbA1c ≥ 7 % ont ete recherches separement pour les patients DT1 et DT2. Pour les DT1, les principaux facteurs associes a une valeur haute de HbA1c des 1 008 patients DT1 etaient un score HFS > + 1DS (odds ratio [OR] 3,5 ; Intervalle de confiance 95 % [IC95] 1,9–6,4) et un score HFS entre − 1 et + 1DS (OR 2,8 ; IC95 1,7–4,7) vs un score HFS faible ( 10 ans (OR 1,8 ; IC95 1,3–2,5). Pour les DT2, le score HFS n’etait plus significatif dans le modele multivarie. Les principaux facteurs correles a la survenue d’une hypoglycemie severe etaient la presence d’antecedents d’hypoglycemie (OR 3,8 ; IC95 1,4–10,6), le diabete de type 1 (OR 1,8 ; IC95 1,3–2,5), le score HFS > + 1DS vs Conclusion La peur des hypoglycemies semble etre tres correlee a la fois aux valeurs hautes de HbA1c chez les DT1 et egalement a la survenue d’hypoglycemie severe chez les patients DT1 et DT2.

We examined the influence of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality in patients with heart failure of both ischaemic or non-ischaemic origin. Eleven, randomized, placebo-controlled trials of ACE inhibitors involving 1266 patients were selected. The follow-up period varied from 3 to 6 months. Four different ACE inhibitors were used in the 11 clinical trials. A total of 679 patients presented with an ischaemic heart failure and 587 with a non-ischaemic heart failure. Meta-analysis, performed for both subgroups, showed that mortality was significantly decreased in the ischaemic subgroup only (ischaemic group: odds ratio 0.45; 95% confidence interval 0.28 to 0.71; non-ischaemic subgroup: odds ratio 0.7; 95% confidence interval 0.4 to 1.5). Although the two odds ratio are not significantly different, further randomized, placebo-controlled trials with ACE inhibitors are required in order to determine more precisely the benefit/risk ratio in patients with non-ischaemic heart failure.

Multivariate analysis of 1H-NMR spectra of blood sera was reported previously to predict angiographically defined advanced coronary artery disease (CAD) with90% accuracy and specificity. The analysis depended mainly on the major lipid regions of the spectra, but many variables, including gender and drug treatment, affect lipid composition and are potential confounders. We have determined the predictive power of the same methodology for angiographically defined CAD using plasma samples from groups of male patients, classified by statin treatment, who had normal coronary arteries (NCAs) or CAD. Predictions for NCA and CAD groups were only 80.3% correct for patients not treated with statins and 61.3% for treated patients, compared with random correct predictions of 50%. A confidence limit of99% was achieved for 36.2% of predictions for untreated groups and 6.2% for treated groups. Detection of CAD by 1H-NMR with99% confidence was therefore very weak compared with angiography.

OBJECTIVE—The purpose of this study was to assess patients’ and physicians’ compliance with ACE inhibitor treatment, by measuring an endogenous biomarker of ACE inhibition, urinary N-acetyl-Ser-Asp-Lys-Pro (AcSDKP), in the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) trial, which compared ramipril (1.25 mg o.d.) with placebo in 4,912 patients with type 2 diabetes and microalbuminuria/proteinuria. RESEARCH DESIGN AND METHODS—The urine AcSDKP-to-creatinine ratio was measured blind to treatment in all participants who completed follow-up and provided spot urine samples (n = 1,871). RESULTS—The median urinary AcSDKP-to-creatinine ratio was six times higher for ramipril than for placebo. Urinary AcSDKP-to-creatinine ratios displayed a bimodal distribution in both groups, with a very large intergroup overlap. Based on cluster analysis, we defined truly adherent ramipril patients as those with a ratio ≥4 nmol/mmol and truly adherent placebo patients as those with a ratio CONCLUSIONS—The systematic use of spot urinary AcSDKP determination facilitated the detection of defects in compliance with ACE inhibitor treatment in both patients and physicians. Urinary AcSDKP measurement could be a useful biomarker for assessing compliance with ACE inhibition in the routine care of diabetic patients.

Aims It is unclear whether the protection observed in human heart following repetition of brief episodes of ischaemia is due to opening of coronary collaterals or to ischaemic preconditioning. We investigated whether the improvement in ST segment change following repeated episodes of brief ischaemia during coronary angioplasty is due to preconditioning when the size of the area at risk and the collateral flow are taken into account. Methods and results Thirty-six patients underwent percutaneous transluminal coronary angioplasty. Intracoronary ST segment changes were measured throughout the procedure and used as an endpoint. The size of the area at risk and the collateral perfusion within the ischaemic bed were measured using single photon emission computerized tomography (SPECT). Mean ST segment shift observed in all patients significantly decreased from 11.0±2.6 mm during the first balloon inflation to 8.5±2.3 mm during the second inflation. This protective effect occurred in the absence of any change in the size of the area at risk (mean: 46±5% of LV) and of the collateral perfusion to the ischaemic zone (mean: 23±4% of flow in the non-ischaemic zone). Conclusion These results suggest that ischaemic preconditioning does occur during repeated brief coronary artery occlusion in the human heart.

What is the place of fish oils in the care of coronary heart disease (CHD) patients? As several clinical trials have already addressed this question without giving definitive answers, we did a meta-analysis of trials regarding the efficacy of omega-3 fatty acids in preventing cardiovascular mortality and morbidity. We searched the MEDLINE (1966-2003), EMBASE databases, proceedings abstracts and references of reviewed articles. Randomized controlled trials (RCTs) of the efficacy of omega-3 fatty acids among adults with recent or acute myocardial infarction (MI), or angina were selected. Two reviewers abstracted data independently. Five relevant outcomes, mortality from all causes, fatal and non-fatal MI, non-fatal stroke and angina, were measured. Data were synthesized using a fixed effect model. Ten RCTs with 14,727 patients were included. No significant heterogeneity was detected. Daily intake of omega-3 fatty acids for a mean duration of 37 months decreased all causes of mortality by 16% (relative risk 0.84, 95% confidence interval [0.76; 0.94]) and the incidence of death due to MI by 24% (0.76, [0.66; 0.88]). No significant effect was found for the other outcomes. Because of the suboptimal quality of the studies included into the meta-analysis and the absence of data in patients receiving statins, these results do not justify adding fish oils systematically to the heavy pharmaceutical assortment already recommended in CHD patients.

Arterial stiffness is a strong determinant of cardiovascular risk. Pulse wave velocity (PWV) is an index of arterial stiffness, and its prognostic value has been repeatedly emphasized. The purpose of the present study was to assess the effect of heart rate (HR) on PWV. Twenty-two subjects with a mean age of 77.8±8.4 (SD) years and permanent cardiac pacing were studied. In each subject, PWV was measured at 5 different pacing frequencies in the same session (60, 70, 80, 90, 100 bpm), the order of the various frequencies being randomly determined. Furthermore, to test the reproducibility, a repeat measurement of PWV was obtained in one randomly selected frequency. Blood pressure (BP) was measured by conventional means at each pacing frequency. PWV appeared fairly reproducible because no significant difference was disclosed between the 2 measurements obtained at the same HR level ( P =0.5) and both measurements were strongly correlated ( r =0.87, P P =0.01). This study demonstrates that HR is an important factor in the intraindividual variation of PWV in elderly subjects. This raises methodological concern about the measurement of this parameter. Standardizing PWV for HR level seems mandatory if one wants to interpret PWV changes in clinical trials or in the follow-up of patients.

Introduction L'hypoglycemie est un probleme majeur dans la prise en charge du diabete, notamment chez les patients âges. Tres peu de donnees etant disponibles chez les patients de plus de 75 ans traites par insuline, une sous-analyse issue de l'etude DIALOG a ete menee afin de determiner la frequence et les consequences des hypoglycemies dans cette population. Patients et methodes L'etude DIALOG est une etude observationnelle, prospective, multicentrique, francaise. 370 endocrinologues et 320 generalistes ont inclus consecutivement 4 424 patients diabetiques de type 1 (DT1) ou 2 (DT2), traites par insuline depuis plus d'un an. Ils leur ont remis un auto-questionnaire afin de noter prospectivement durant 1 mois les hypoglycemies, classees selon les criteres ADA. Les facteurs predictifs des hypoglycemies ont ete analyses avec un modele de regression multivarie. Resultats Parmi les 3 048 patients ayant rempli le suivi prospectif de l'etude DIALOG, 1 731 etaient des DT2 dont 16,7 % (n=419) âges de 75 ans et plus. Les caracteristiques de ces derniers etaient : âge 80,2±4,1 ans, IMC 29,0±5,1kg/m 2 , HbA1c 7,8±1,0 %, anciennete du diabete 20,9±10,7 ans. Les frequences des hypoglycemies confirmees chez les DT2, DT2 2 (OR : 1,75) et une anciennete de mise sous insuline > 10 ans (OR : 1,72). Conclusion DIALOG est une vaste etude prospective des hypoglycemies en vie reelle qui montre une frequence elevee des hypoglycemies confirmees, comparable a celle de la population generale de l'etude, chez les patients DT2 âges, traites par insuline. Les antecedents d'hypoglycemies apparaissent comme le principal facteur predictif d'hypoglycemies.

Introduction L’evaluation de la peur de l’hypoglycemie chez le diabetique est importante, mais peu d’outils sont disponibles en pratique clinique. Le questionnaire valide HFS-II (Hypoglycemia Fear Survey-II) mesure la crainte du risque de survenue d’hypoglycemies en evaluant les consequences de l’hypoglycemie et le comportement du patient en retour (questions 1 a 15), ainsi que le degre d’inquietude liee a l’hypoglycemie (questions 16 a 33). L’objectif de cette analyse est d’obtenir un questionnaire HFS-II court, facilement utilisable en pratique clinique, tout en conservant la meme interpretation. Patients et methodes Les donnees de 2 787 diabetiques insulinotraites ayant complete le questionnaire HFS-II dans l’etude observationnelle DIALOG ont ete utilisees pour reduire le nombre de questions en 3 etapes : elimination des questions ayant un taux de reponses au plancher > 60 %, puis des questions les moins discriminantes dans l’analyse en composantes principales. Les scores du questionnaire ainsi reduits ont ensuite ete repartis en 3 classes : « + 1DS ». Toutes les combinaisons de questions restantes ont ete testees afin de reduire au maximum le questionnaire tout en maintenant un seuil de concordance de 80 % entre le questionnaires initial, celui reduit au global et les sous-scores. Resultats Le questionnaire obtenu compose de 8 questions (4 par domaine) permet d’obtenir un pourcentage de patients classes dans la meme categorie de DS de 85,6 % (respectivement 80,2 % et 80,3 % dans les domaines comportement et inquietudes). Aucun patient n’est passe d’une classe extreme a l’autre, (i.e. de « + 1DS » et inversement). Les differences de score observees entre sous-groupes (notamment DT1 vs DT2) avec le questionnaire initial sont conservees avec le questionnaire reduit. Conclusion La version reduite du questionnaire HFS-II a 8 questions permet de conserver la majeure partie de l’information et pourrait etre utilisee en pratique clinique quotidienne pour evaluer la peur de l’hypoglycemie.

Purpose: The aim was to investigate in patients receiving doxorubicin whether any alteration in myocardial oxidative metabolism or blood flow as assessed by positron emission tomography (PET) could be observed either after the first dose of the drug, or during its chronic administration. Methods: Six female non-heart-failure cancer patients treated with doxorubicin were included in a longitudinal study. Resting radionuclide cineangiography and PET scanning with carbon-11 acetate were performed the day before the initiation of doxorubicin treatment at a dosage of 50 mg/m2 every 3 weeks, and 3 weeks after the cumulative administration of 300 mg/m2 (chronic toxicity). In addition, PET was performed 24 h after the first administration of doxorubicin (evaluation of acute toxicity). Myocardial oxidative metabolism and blood flow were assessed by PET (acute and chronic toxicity), and left ventricular ejection fraction was measured by radionuclide angiography (chronic toxicity). Results: Using PET for both acute and chronic toxicity evaluations, no significant effect of doxorubicin was observed either on the flux through the tricarboxylic acid (TCA) cycle or on myocardial blood flow. However, systolic left ventricular function showed a small but significant impairment after the administration of 300 mg/m2 of doxorubicin. Conclusions: Other hypotheses should be explored to better explain the predominant mechanisms of the cardiotoxicity of anthracyclines in humans.

OBJECTIVE The purpose of this study was to test the robustness of the measurement of left ventricle mass (LVM), using Devereux's formula, in the presence of a rapid change in left ventricular volume induced by nitroglycerin. DESIGN Forty-eight healthy volunteers with excellent echocardiographic recordings were included. The intrapatient variability of LVM measurement was assessed by two consecutive echocardiograms. The intraobserver reproducibility was assessed by the rereading of 19 echocardiograms by the same observer. The effects of nitroglycerin were compared with those of a placebo in a double-blind random manner on, the left ventricular internal dimension in diastole (LVIDd), the interventricular septum thickness, the posterior wall thickness and the LVM. RESULTS It was shown that both the intrapatient and the intraobserver reproducibility were high. Nitroglycerin induced a significant decrease in LVIDd compared with placebo (-0.21 +/- 0.24 versus 0.01 +/- 0.21 cm, respectively, P < 0.01) and a non-significant increase in wall thickness. These variations were negatively correlated with each other (r= -0.58, P< 0.01). Despite the change of ventricular dimensions, the variation of LVM induced by nitroglycerin was not significantly different from that induced by placebo (2.0 +/- 16.0 versus 4.7 +/- 17.0 g, respectively, not significant) and close to the intrapatient variability. CONCLUSION This experiment failed to demonstrate any influence of a rapid variation of ventricle size on the calculation of LVM with the Penn convention and strongly supports the robustness of the method in vivo.

Objectif L'hypoglycemie est le principal effet secondaire de l'insulinotherapie. L'etude DIALOG avait pour objectif de determiner la frequence des hypoglycemies chez les patients diabetiques de type 1 (DT1) et de type 2 (DT2) insulino-traites. Cette analyse vise a identifier les facteurs predictifs de la survenue des hypoglycemies. Patients et methodes DIALOG est une etude observationnelle, multicentrique, au cours de laquelle les medecins specialistes et generalistes remplissaient un cahier d'observation et remettaient un auto-questionnaire prospectif aux patients, analysant les hypoglycemies survenues durant 1 mois de suivi. Une regression logistique multivariee a ete conduite afin d'etudier l'association entre differents parametres a l'inclusion et la survenue des hypoglycemies. Resultats Parmi les 4424 patients inclus, l'analyse a ete menee chez 912 patients DT1 et 1677 DT2 (les patients sous pompe a insuline n'etant pas dans l'analyse). Chez les DT1, les principaux facteurs predictifs du risque d'hypoglycemie etaient les suivants : nombre d'injections d'insuline >2/jour (Odds Ratio(OR)=2,182 ; Intervalle de Confiance a 95% (IC95)=1,377 3,457), sexe feminin (OR=1,747 ; IC95=1,185–2,575), âge 2 (OR=2,151; IC95=1,3003,558), duree d'insulinotherapie > 10 ans (OR=2,087 ; IC95=1,416–3,078), antecedents d'hypoglycemies globales (OR=8,625 ; IC95=4,096–18,162). Inversement, la presence de plaies chroniques du pied (OR=0,462 ; IC95=0,216–0,989) et une dyslipidemie (OR=0,565 ; IC95=0,380–0,840) etaient associees a une diminution du risque d'hypoglycemies. Chez les DT2, les facteurs predictifs d'hypoglycemie etaient le nombre d'injections d'insuline : 2 versus 1 injection/jour (OR=1,381 ; IC95=1,038–1,837) et > 2 versus 1 injection/jour (OR=2,120; IC95=1,672–2,687), un IMC 2 (OR=1,309 ; IC95=1,065–1,608), une duree d'insulinotherapie > 10 ans (OR=1,596 ; IC95=1,251–2,037), des antecedents d'hypoglycemies globales (OR=3,880 ; IC95=2,767–5,440) et l'absence de coronaropathie (OR=1,436 ; IC95=1,133–1,820). Conclusion Chez les patients DT1 et DT2, les facteurs predictifs d'hypoglycemies sont : l'absence d'obesite ( 10 ans), le nombre d'injections (>2/jour) et surtout l'existence d'hypoglycemies anterieures.

News p 561 Education and debate p 592 On 9 February 2000 alosetron (marketed as Lotronex by GlaxoSmithKline), a type 3 serotonin (5-HT3) receptor antagonist, was approved by the US Food and Drug Administration (FDA) for the treatment of patients with irritable bowel syndrome, a benig though unpleasant disorder that affects one in five adults in the industrialised world.1 By November 2000, the FDA had received 49 reports of ischaemic colitis and 21 of severe constipation related to the drug, resulting in 44 admissions to hospital, 10 surgical interventions, and 3 deaths.2 The drug was withdrawn from the market by its sponsor. Severe adverse events continued to be reported for some time, with a final total of 84 instances of ischaemic colitis, 113 of severe constipation, 143 admissions to hospital, and 7 deaths.3 On 7 June 2002, however, the FDA issued a supplemental new drug application that permits marketing of alosetron through a prescribing programme for treating women with irritable bowel syndrome whose main symptom is severe diarrhoea (5% of patients). Doctors will have to sign an attestation of qualification and acceptance of …

An effect model is a function that defines the relationship between the clinical efficacy of a treatment and specific covariates. The simplest effect model defines the probability of failure in treated patients as a linear function of the probability for these patients if they received no treatment. We used this approach to explore the effects of Class I antiarrhythmic agents in patients after myocardial infarction. Evidence from one large trial, the Cardiac Arrhythmic Suppression Trial (CAST), and the pooling of data from several smaller trials suggests that these agents have harmful effects in postmyocardial infarction patients. The relevance of results from pooled data is dependent on the homogeneity of the trials and is assessed by a heterogeneity test that is dependent on the analytical method used, i.e., odds ratio or rate difference methods, which correspond to two different effect models. We have developed an effect model that considers both iatrogenic effects of these drugs, i.e., depression of ventricular function and arrhythmogenic effects. When applied to the data from 13 published trials (including CAST), we found that these drugs may be beneficial in high-risk patients (with a 1-year mortality rate of > or = 15%) and that the background lethal iatrogenic effect is likely to affect low- and very low-risk patients (1-year mortality rate of < or = 5%). The accuracy of the proposed model was confirmed with use of the results from the recent CAST II study.

Propranolol pretreatment (0.1 mg X kg-1) significantly increased the lengthening induced by diltiazem (0.15 mg X kg-1 + 0.01 mg X kg-1 X min-1, 20 min) of the A-H interval of His bundle potential recordings in the dog. In the presence of propranolol, diltiazem also significantly increased the atrioventricular effective refractory period. The results suggest the possible occurrence of AV blocks as a result of the use of a diltiazem-beta blocker combination in clinical practice.

1 During total cardiopulmonary bypass, acetylcholine-, isoprenaline-, ouabain- and quinidine-induced variations in the atrial and ventricular rates of fibrillation were studied and compared with the variations in effective refractory periods (ERP) of atrial and ventricular contractile tissue obtained under the same experimental conditions. 2 Acetylcholine significantly shortened the ERP and accelerated the rate of fibrillation in the atrium but did not provoke any change in ventricular tissue. A parallel decrease in atrial and ventricular ERP and a parallel increase in atrial and ventricular rates of fibrillation were observed with isoprenaline. 3 Ouabain exerted a biphasic effect on the atrium, with an initial decrease in the ERP and an initial acceleration of the rate of fibrillation. It produced only a slight decrease in the ventricular ERP and no significant variation in the ventricular rate of fibrillation. 4 Quinidine induced a greater increase in the ERP and a greater slowing of the rate of fibrillation in the atrium than in the ventricle. 5 The variations in percentage change of refractoriness and rate of fibrillation were strictly correlated: r = 0.89 (P less than 0.001); the equation of the regression line was y = --0.86 x --2.98.

Carbocromen prevents to some extent, particularly in subendocardial layer, carbohydrate cardiac metabolism alterations induced by the ischemia obtained by intermittent occlusion of left coronary artery.

To describe the present status of type 1 diabetes care in France and study the relations between clinical and socio-economic variables on one hand and disease management and prevalence of complications on the other hand.A random sample of 365 French specialists in diabetes care performed a cross-sectional study and included consecutively 562 children aged 10-16 and 1691 adults aged 16-45, with more than 2 years of type 1 diabetes. The main outcome measures were the prevalence of complications (retinal, renal, lower-limb, cardiovascular, ketoacidosis); disease management parameters (blood pressure, HbA1c, daily number of insulin injections, frequency of visits to a specialist in diabetes, membership of a patient association); socio-economic status as a score, and treatments received.Retinal complications were rare in children (0.7%) and common in adults (28.3%). 10.2% children and 15.2% adults had micro- or macro-albuminuria, 4.7% adults had plasma creatinineor=150 micromol/L. Only 15% children and 26% adults had HbA1c7%, 86.2% children and 62.7% adults had blood pressure130/85 mmHg; 58% children and 80% adults had at least 3 daily insulin injections. In adults, the risk of experiencing at least one complication was linked significantly with diabetes duration, HbA1c, and socio-economic status. Age, sex, type of insulin therapy, tobacco consumption, and blood pressure control were not significant parameters. Ketoacidosis in the preceding year was only linked with HbA1C and socio-economic status.Although this sample of patients had overall a fair socio-economic status and were followed-up by specialists of diabetes care, metabolic and blood pressure control were not optimal. The care of French type 1 diabetics could probably be improved by a stricter control of glycaemia and blood pressure, and an earlier use of intensive insulin treatment, with a particular focus on adolescents and patients with the lowest socio-economic status.