Influence of diabetes mellitus on heart failure risk and outcome

Our aim is to summarize and discuss the recent literature linking diabetes mellitus with heart failure, and to address the issue of the optimal treatment for diabetic patients with heart failure. THE STUDIES LINKING DIABETES MELLITUS (DM) WITH HEART FAILURE (HF): The prevalence of diabetes mellitus in heart failure populations is close to 20% compared with 4 to 6% in control populations. Epidemiological studies have demonstrated an increased risk of heart failure in diabetics; moreover, in diabetic populations, poor glycemic control has been associated with an increased risk of heart failure. Various mechanisms may link diabetes mellitus to heart failure: firstly, associated comorbidities such as hypertension may play a role; secondly, diabetes accelerates the development of coronary atherosclerosis; thirdly, experimental and clinical studies support the existence of a specific diabetic cardiomyopathy related to microangiopathy, metabolic factors or myocardial fibrosis. Subgroup analyses of randomized trials demonstrate that diabetes is also an important prognostic factor in heart failure. In addition, it has been suggested that the deleterious impact of diabetes may be especially marked in patients with ischemic cardiomyopathy. TREATMENT OF HEART FAILURE IN DIABETIC PATIENTS: The knowledge of the diabetic status may help to define the optimal therapeutic strategy for heart failure patients. Cornerstone treatments such as ACE inhibitors or beta-blockers appear to be uniformly beneficial in diabetic and non diabetic populations. However, in ischemic cardiomyopathy, the choice of the revascularization technique may differ according to diabetic status. Finally, clinical studies are needed to determine whether improved metabolic control might favorably influence the outcome of diabetic heart failure patients

Development of a complex intervention for early integration of palliative home care into standard care for end-stage COPD patients : a phase 0-I study

Background : Research suggests that palliative home care should be integrated early into standard care for end-stage COPD patients. Patients also express the wish to be cared for and to die at home. However, a practice model for early integration of palliative home care (PHC) into standard care for end-stage COPD has not been fully developed. Aim : To develop an intervention for early integration of PHC into standard care for end-stage COPD patients. Methods : We conducted a Phase 0-I study according to the Medical Research Council Framework for the development of complex interventions. Phase 0 aimed to identify the inclusion criteria and key components of the intervention by way of an explorative literature search of interventions, expert consultations, and seven focus groups with general practitioners and community nurses on perceived barriers to and facilitators of early integrated PHC for COPD. In Phase 1, the intervention, its inclusion criteria and its components were developed and further refined by an expert panel and two expert opinions. Results : Phase 0 resulted in identification of inclusion criteria and components from existing interventions, and barriers to and facilitators of early integration of PHC for end-stage COPD. Based on these findings, a nurse-led intervention was developed in Phase I consisting of training for PHC nurses in symptom recognition and physical therapy exercises for end-stage COPD, regular visits by PHC nurses at the patients' homes, two information leaflets on selfmanagement, a semi-structured protocol and follow-up plan to record the outcomes of the home visits, and integration of care by enabling collaboration and communication between home and hospital-based professional caregivers. Conclusion : This Phase 0-I trial succeeded in developing a complex intervention for early integration of PHC for end-stage COPD. The use of three methods in Phase 0 gave reliable data on which to base inclusion criteria and components of the intervention. The preliminary effectiveness, feasibility and acceptability of the intervention will be subsequently tested in a Phase II study

238 A randomized, double-blind placebo-controlled study of NV1FGF gene therapy in critical limb ischemia patients (TAMARIS Study) Rationale, design and baseline patient characteristics

BackgroundPatients with critical limb ischemia (CLI) unsuitable for revascularization have a high rate of amputation and mortality (30% and 25% at 1 year respectively Local gene therapy using plasmid DNA encoding acidic fibroblast growth factor (NV1FGF, riferminogene pacaplasmid) showed promising results in a phase II trial on amputation free survival. This report provides the rationale, design and baseline characteristics of CLI patients enrolled to the pivotal phase III trial (TAMARIS). It also describes baseline characteristics by diabetes status and region of origin.Table: Comparison of 6 modes of ABI calculation to predict the 5-years mortality (abstract 237).ABI mode of calculationHigh/HighMean/HighLow/HighHigh/MeanMean/MeanLow/MeanAUC0.632*0.6200.6150.6100.6180.598Sensitivity with 0.9055.7%56.7%60.4%53.6%60.8%58.8%Specificity with 0.9065.1%62.3%60.2%63.6%58.5%58.6%Optimal cutpoint0.940.970.921.000.970.92Sensitivity for optimal cutpoint63.9%72.2%64.6%72.2%74.2%62.9%Specificity for optimal cutpoint60.3%50.6%58.7%48.3%50.3%57.5%*p<0.05 vs. High/Mean and Low/MeanMethodsAn international, double-blind, placebo-controlled, randomized study included 525 CLI patients worldwide who were unsuitable for revascularization and had non-healing skin lesions, to evaluate whether repeated intramuscular administration of NV1FGF results in reduction of major amputations or deaths at 1 year.ResultsMean age of the population was 70 ± 10 years including 70% males and 53% diabetic patients. Fifty four percent of the population had previous lower extremity revascularization and 22% had previous minor amputation of the index leg. Ninety six percent of patients had an ankle pressure < 70mmHg and/or a toe pressure < 50mmHg or a TcPO2 < 30mmHg. In 94% the index leg had distal occlusive disease affecting arteries below the knee. Statins were prescribed in 54% of patients, and antiplatelet drugs in 80%. Variation in region of origin resulted in only minor demographic imbalance. Patients with diabetes had more risk factors including history of coronary artery disease, but were similar to non-diabetic patients regarding limb haemodynamics and vascular lesions.ConclusionThe clinical and vascular anatomy presentation of patients with CLI with ischemic skin lesions who were unsuitable for revascularization was homogeneous with little imbalance according to region of origin or diabetic status. The findings from this large CLI cohort are important for the understanding of the epidemiology of the disease

934-28 Sensitivity and Specificity of Angiographic Markers for Thrombus: A Prospective Comparison with Angioscopy

The limitations of angiography for the detection of intracoronary thrombus are well recognized. Between November 1991 and July 1994, we performed 402 angioscopy procedures in 225 vessels in 202 patients, with the Image-Cath (Baxter).We performed a prospective study in 190 of these patients, who had an interpretable angioscopy performed just before PTCA to determine the sensitivity and specificity of predetermined angiographic criteria that are considered to be indicative of the presence of intracoronary thrombus. Angiographically verified thrombus was used as the gold standard for comparison. Lesions were classified on angiography (2 orthogonal views) by independent observers. The presence of an intraluminal filling defect, of overhanging edges, of haziness, or of ulceration were noted. The characteristic ulceration was not mutually exclusive of the other 3 characteristics.Of 15 filling defects on angiography 14 (93%) had thrombus on angiography; in the 23 lesions with overhanging edges 19 (83%) had thrombus on angioscopy; in the 27 ulcerated lesions 21 (78%) had angioscopic thrombus; in the 6 lesions that were hazy on angiography 5 had angioscopic thrombus.AngioscopyThrombus+Thrombus-AngiographyThrombus+4512Thrombus-4093In our model, using 5 prespecified angiographic characteristics, angiography had high specificity (89%) but relatively low sensitivity (53%) for the detection of thrombus compared to angioscopy

A common variant of endothelial nitric oxide synthase (Glu298Asp) is associated with collateral development in patients with chronic coronary occlusions

BACKGROUND: Experimental studies support an important role for endothelial nitric oxide synthase (eNOS) in the regulation of angiogenesis. In humans, a common polymorphism exists in the eNOS gene that results in the conversion of glutamate to aspartate for codon 298. In vitro and in vivo studies have suggested a decreased NOS activity in patients with the Asp(298 )variant. We hypothesized that a genetic-mediated decreased eNOS activity may limit collateral development in patients with chronic coronary occlusions. METHODS: We selected 291 consecutive patients who underwent coronary angiography and who had at least one chronic (>15 days) total coronary occlusion. Collateral development was graded angiographically using two different methods: the collateral flow grade and the recipient filling grade. Genomic DNA was extracted from white blood cells and genotyping was performed using previously published techniques. RESULTS: Collateral development was lower in patients carrying the Asp(298 )variant than in Glu-Glu homozygotes (collateral flow grade: 2.64 ± 0.08 and 2.89 ± 0.08, respectively, p = 0.04; recipient filling grade: 3.00 ± 0.08 and 3.24 ± 0.07, respectively, p = 0.04). By multivariable analysis, three variables were independently associated with the collateral flow grade: female gender, smoking, and the Asp(298 )variant (p = 0.03) while the Asp(298 )variant was the sole variable independently associated with the recipient filling grade (p = 0.03). CONCLUSION: Collateral development is lower in patients with the Asp(298 )variant. This may be explained by the decreased NOS activity in patients with the Asp(298 )variant. Further studies will have to determine whether increasing eNOS activity in humans is associated with coronary collateral development

140 Impact of TAVI with the Edwards-SAPIEN endoprosthesis on mitral regurgitation: results of a serial echocardiography assessment

PurposeThe impact of transcatheter aortic valve implantation (TAVI) on mitral regurgitation (MR) is controversial. Two recent publications have reported improvement in MR grades following implantation of the Edwards-SAPIEN endoprosthesis. These findings were not replicated with the Core-Valve. The time course of improvement in MR grades with the Edwards-SAPIEN valve has not been described on an individual patient basis and the potential mechanisms of benefit are unclear. The aim of this study was to assess the acute and intermediate changes in MR severity after TAVI with the Edwards-SAPIEN endoprosthesis.MethodsEchocardiography was performed in 22 consecutive patients before and after treatment, and at 1 month follow-up. MR was assessed by color flow mapping and was graded as none, mild, moderate, or severe. MR was defined as organic or functional.ResultsThe aortic valve area increased from pretreatment 0.72cm2 to post-treatment 1.87cm2 and postdischarge 1.81cm2 (P<0.0001). Before intervention MR was present in 73% of the patients. It was mild, moderate, or severe in 36% (n=8), 32% (n=7), and 4% (n=1) respectively. MR was defined as organic in 6 patients (27%) and functional in 10 patients (45%). Compared to baseline, MR grades improved by 1 month (p for trend=0.01). This benefit was secondary to a reduction in regurgitation grades in 50% of patients with an MR at baseline (n=6), while no worsening was observed in the other patients with an MR (n=6) and no occurrence of MR was observed in patients without MR (n=6). A trend for a greater improvement in MR grade was observed in patients with functional MR (n=7, − 1.00) compared to those with an organic MR (n=5, − 0.294; p=0.10).ConclusionIn consecutive patients with a successful implantation of an Edwards-SAPIEN valve a significant improvement in MR was observed. This benefit was secondary to an improvement in 50% of patients with an MR and no worsening in the others

Individual participant data analysis of two trials on aldosterone blockade in myocardial infarction

Background: Two recent randomised trials studied the benefit of mineralocorticoid receptor antagonists (MRAs) in ST-segment elevation myocardial infarction (STEMI) irrespective or in absence of heart failure. The studies were both undersized to assess hard clinical endpoints. A pooled analysis was preplanned by the steering committees. Methods: We conducted a prespecified meta-analysis of patient-level data of patients with STEMI recruited in two multicentre superiority trials, randomised within 72 hours after symptom onset. Patients were allocated (1:1) to two MRA regimens: (1) an intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) versus standard therapy or (2) oral eplerenone (25–50 mg) versus placebo. The primary and key secondary outcomes, all-cause death and the composite of all-cause death or resuscitated sudden death, respectively, were assessed in the intention-to-treat population using a Cox model stratified on the study identifier. Results: Patients were randomly assigned to receive (n=1118) or not the MRA regimen (n=1123). After a median follow-up time of 188 days, the primary and secondary outcomes occurred in 5 (0.4%) and 17 (1.5%) patients (adjusted HR (adjHR) 0.31, 95% CI 0.11 to 0.86, p=0.03) and 6 (0.5%) and 22 (2%) patients (adjHR 0.26, 95% CI 0.10 to 0.65, p=0.004) in the MRA and control groups, respectively. There were also trends towards lower rates of cardiovascular death (p=0.06) and ventricular fibrillation (p=0.08) in the MRA group. Conclusion: Our analysis suggests that compared with standard therapy, MRA regimens are associated with a reduction of death and death or resuscitated sudden death in STEMI

Aldosterone, atherosclerosis and vascular events in patients with stable coronary artery disease

AbstractBackground and aimsPlasma aldosterone has been associated with all-cause and cardiovascular mortality in high-risk cardiovascular populations, including patients with heart failure, myocardial infarction and high-risk coronary artery disease (CAD) patients. In the present study, we evaluated the association of plasma aldosterone levels with vascular events in a large prospective cohort of stable CAD patients recruited in an outpatient setting. Moreover, we investigated the relationship between aldosterone and atherosclerotic burden.Methods and resultsBaseline plasma aldosterone levels were measured in 2699 subjects with CAD (mean age 60±10years, 82% male). During a median follow-up of 4.7years, 308 (11%) patients died, of which 203 were from a vascular cause. Vascular endpoints of myocardial infarction, ischemic stroke or vascular death occurred in 355 (13%) patients. Multivariable Cox regression analysis was performed, adjusting for multiple confounders. Aldosterone (median 96pg/mL, interquartile range 70–138pg/mL, normal range 58–362pg/mL) was independently associated with major vascular events (hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.13–2.15) and vascular mortality (HR 1.95, 95% CI 1.27–3.00). By multivariable regression analysis, aldosterone was also associated with the presence of atherosclerosis in additional vascular territories (cerebrovascular disease and/or peripheral artery disease) (p=0.026).ConclusionsIn patients with stable coronary artery disease, plasma aldosterone is independently associated with the risk of major vascular events and vascular mortality and with atherosclerotic burden

The HD 192263 system: planetary orbital period and stellar variability disentangled

As part of the Transit Ephemeris Refinement and Monitoring Survey (TERMS), we present new radial velocities and photometry of the HD 192263 system. Our analysis of the already available Keck-HIRES and CORALIE radial velocity measurements together with the five new Keck measurements we report in this paper results in improved orbital parameters for the system. We derive constraints on the size and phase location of the transit window for HD 192263b, a Jupiter-mass planet with a period of 24.3587 \pm 0.0022 days. We use 10 years of Automated Photoelectric Telescope (APT) photometry to analyze the stellar variability and search for planetary transits. We find continuing evidence of spot activity with periods near 23.4 days. The shape of the corresponding photometric variations changes over time, giving rise to not one but several Fourier peaks near this value. However, none of these frequencies coincides with the planet's orbital period and thus we find no evidence of star-planet interactions in the system. We attribute the ~23-day variability to stellar rotation. There are also indications of spot variations on longer (8 years) timescales. Finally, we use the photometric data to exclude transits for a planet with the predicted radius of 1.09 RJ, and as small as 0.79 RJ.Comment: 9 pages, 6 tables, 6 figures; accepted to Ap