Lipid lowering on progression of mild to moderate aortic stenosis: meta-analysis of the randomized placebo-controlled clinical trials on 2344 patients

Background

Aortic stenosis (AS) is believed to develop through an inflammatory similar to the atherosclerosis process. Based on findings from animal studies and uncontrolled clinical studies, lipid-lowering therapy with a statin is postulated to slow this process. Randomized trials, however, reported neutral results. This meta-analysis of randomized lipid trials on patients with AS examined the effects of treatment on AS progression and clinical outcomes.

Methods

Echocardiographic measures of AS (aortic valve jet velocity, peak and mean valve gradients, and aortic valve area) were pooled and clinical outcomes were evaluated in 4 randomized placebo controlled trials (N = 2344).

Results

Although active treatment with statin therapy was associated with highly significant 50% reduction in low-density lipoprotein cholesterol levels, there were no statistical differences between active and placebo groups in any of the echocardiographic indicators of AS severity: annual increase in AS velocity was 0.16 ± 0.28 m/sec, and mean gradient was 2.8 ± 3.0 mm Hg. Each trial reported no differences in clinical outcomes between the 2 treatment groups. Substantial events rates (6.6% aortic valve surgery and 1.2% cardiovascular deaths per year in SEAS with follow-up of 4.4 years and 5.8% aortic valve surgery and 0.7% cardiovascular deaths per year in ASTRONOMER over 3.5 years) were observed in these patients despite the relatively mild disease.

Conclusion

The current data do not support the hypothesis that statin therapy reduces AS progression. Patients with mild to moderate AS may require closer follow-up because despite the less severe disease in these trials, event rates remain substantial.     

Long-term pediatric outcome of isolated discrete subaortic stenosis

Background

The management of pediatric discrete subaortic stenosis remains controversial.

Objectives

Document the natural history and surgical outcomes for discrete subaortic stenosis to adolescence.

Methods

Retrospective review of clinical and echocardiographic findings in 74 patients diagnosed in childhood between 1985 and 1998.

Results

Twenty-five patients were followed only medically for 9.4 ± 0.9 years to 15.9 ± 0.6 years of age. Their echocardiographic left ventricular outflow peak gradient did not progress, 19 ± 1.4 (SEM) vs 20 ± 2.3 mm Hg. The proportion with aortic insufficiency (AI) increased (4% to 52%). Forty-nine patients were operated for discrete subaortic stenosis at 7.8 ± 0.6 years. Their peak gradient at diagnosis was 36 ± 3 mm Hg with AI in 33%. Preoperatively their peak gradient progressed to 60 ± 5 mm Hg with AI in 82%. Assessment 6.2 ± 0.5 years postoperativly showed a peak gradient of 14 ± 2 mm Hg with AI in 88%. Ten patients required reoperation for recurrent discrete subaortic stenosis, 3 acquired complete heart block, and 1 developed endocarditis. There was no mortality. At diagnosis, surgical patients were younger, had greater peak gradients, and greater incidence of AI, than those followed only medically. The progression of discrete subaortic stenosis was positively associated with severity of obstruction and negatively associated with older age at diagnosis. The risk of having surgery over time was associated with greater preoperative obstruction and presence of AI.

Conclusions

Many pediatric patients with mild discrete subaortic stenosis exhibit little progression of obstruction and need not undergo immediate surgery. Others with more severe stenosis may progress precipitously and will benefit from early resection.     

Use of gadolinium as contrast agent in endoscopic retrograde cholangiopancreatography in patients with iodine allergy

Introduction

Radiologic contrasts are required during endoscopic retrograde cholangiopancreatography (ERCP). The most frequently used are iodine-based contrast media. Controversy still surrounds the optimal strategy in patients with previous adverse reactions to iodine contrasts that need to undergo an ERCP.

Objective

To evaluate the safety and efficacy of a gadolinium-derived contrast medium in patients with previous reactions to iodine-derived agents during ERCP.

Material and methods

Thirteen ERCP were performed in 11 patients with well-established adverse reactions to iodine compounds. ERCP was carried out with gadobutrol, a non-ionic gadolinium compound and without prophylaxis.

Results

In all patients, ERCP were satisfactorily completed. Thirteen cholangiograms and one pancreatogram were obtained. All procedures were technically successful, allowing diagnosis and endotherapy. The quality of the images was good, similar to those obtained with standard contrast media, and did not represent a limitation. No contrast-related adverse events were observed, and there were no post-ERCP complications.

Conclusions

Gadolinium-derived agents are a safe and effective alternative in iodine-allergic patients.     

Clinically important differences in health status for patients with heart disease: an expert consensus panel report

Background

The purpose of the study was to develop clinically important difference (CID) standards for patients with coronary artery disease and congestive heart failure that identify small, moderate, and large intraindividual changes with time in a modified version of the Chronic Heart Failure Questionnaire (CHQ) and the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36, version 2). Prior work in ascertaining important difference standards for the CHQ have centered on patient-perceived changes. No important difference standards for the SF-36 have been published for patients with heart disease. This development of CIDs would facilitate the use of health status measures in daily clinical decision-making.

Methods

We used a modification of the RAND Appropriateness Method to assemble and guide a 9-member consensus panel of physicians with substantial experience in using the CHQ or the SF-36 among patients with heart disease.

Results

On the basis of their own experience using these measures and an extensive review of articles describing the development and use of these instruments, the expert panel achieved consensus on small, medium, and large clinically relevant changes in scores for the CHQ and SF-36. The CID standards established by this panel were slightly higher than the minimal important difference standards previously established for the CHQ using patient-perceived changes.

Conclusions

The CID standards established by this expert panel provide an important and useful tool for determining whether routine clinical health status assessments will benefit patients and enhance physicians' decision-making capacity in clinical settings.     

A randomized,double-blinded,placebo-controlled,dose-ranging study measuring the effect of an adenosine agonist on infarct size reduction in patients undergoing primary percutaneous transluminal coronary angioplasty: the ADMIRE (AmP579 Delivery for Myocardial Infarction REduction) study

Background

Evidence suggests that myocardial ischemic preconditioning and reperfusion injury may be mediated by adenosine A1 and A2 receptors. AMP579 is a mixed adenosine agonist with both A1 and A2 effects. In animal models of acute myocardial infarction (MI), AMP579 reduced infarct size at serum levels of 15 to 24 ng/mL.

Methods

The AMP579 Delivery for Myocardial Infarction REduction study evaluated AMP579 in a double-blind, multicenter, placebo-controlled trial of 311 patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) after acute ST-segment elevation MI. Patients were randomly assigned to placebo or to 3 different doses of AMP579 continuously infused over 6 hours. The primary end point was final MI size measured by technetium Tc-99m sestamibi scanning at 120 to 216 hours after PTCA. Secondary end points included myocardial salvage and salvage index at the same time interval (in a subset of patients who underwent baseline technetium Tc-99m sestamibi scan), left ventricular ejection fraction and heart failure at 4 to 6 weeks, duration of hospitalization, and cardiac events at 4 weeks and 6 months.

Results

Final infarct size did not differ among the placebo group and the active treatment groups for either anterior MI or nonanterior MI. In patients with anterior MI, median myocardial salvage was increasingly higher in the groups receiving ascending dosages of AMP579 plus PTCA. Serum levels approaching levels shown to reduce infarct size in animal models were achieved only in the 60-mcg/kg treatment group.

Conclusion

AMP579 was safe at the doses tested, but it did not reduce infarct size. There was a trend toward greater myocardial salvage in treated patients with anterior MI.     

Survey of general practitioners management of erysipelas

Purpose

A few studies only have focused on ambulatory management of erysipelas.

Methods

To assess the diagnostic and therapeutic management of erysipelas by general practitioners, and their adherence to the French Society of Infectious Diseases and Dermatology joint 2000 recommendations, we surveyed 114 general practitioners during a 1 year period (from May 1st, 2005 to April 30th, 2006).

Results

Seventy-three general practitioners accepted to participate to the study and 54 cases of erysipelas were reported. Median age of patients was 63 years (range, 18-94) and sex ratio was 0.77. Lower limbs were affected in 83% out of the cases. A skin lesion was reported in 65% of the cases. None of the 15 doppler ultrasonography that were performed identified deep vein thrombosis. Five patients (9%) were initially hospitalized. Only 18% out of the patients were treated by amoxicillin. Most prescribed antimicrobial agents were pristinamycin (31%) and amoxicillin-clavulanate (27%). Median duration of treatment was 10 days. Six patients received an anti-inflammatory drug. Among the 44 patients who had a follow-up visit, 37 patients (84%) recovered and two patients were hospitalized after this follow-up assessment. Two patients experienced a recurrence of erysipelas during the study.

Conclusion

As previously reported in the literature, outcome of erysipelas after ambulatory management remains excellent, although recommendations are poorly followed.     

Outcomes in patients with chronic kidney disease referred late to nephrologists: a meta-analysis

Purpose

The study purpose was to compare differences in mortality and the duration of hospitalization in patients with chronic kidney disease who are referred early versus late to nephrologists.

Methods

We searched English-language literature from 1980 through December 2005, along with national conference proceedings, the Web of Science Citation Index, and reference lists of all included studies. Twenty-two studies with a total sample size of 12,749 met inclusion criteria.

Results

There was significantly increased overall mortality in the late referral group as compared with the early referral group (relative risk 1.99; 95% confidence interval [CI], 1.66 to 2.39, P <.0001). The duration of hospital stay, at the time of initiation of renal replacement therapy, was greater in the late referred group by an average of 12 days (95% CI, 8.0 to 16.1, P = .0007). Significant heterogeneity was detected for both outcomes.

Conclusion

Timing of referral emerged to be a significant factor impacting homogeneity in the mortality outcome. Our results suggest significantly higher mortality and increased early hospitalization of chronic kidney disease subjects referred late to nephrologists as compared with earlier referred subjects.     

Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats

Aims

Stem cells are a new hope to ameliorate impaired diabetic wound healing. The purpose of this study was to evaluate the effect of adipose tissue derived mesenchymal stem cells (AD-MSCs) on wound healing in a diabetic rat model.

Methods

Twenty-six rats became diabetic by a single intraperitoneal injection of streptozotocin. Six rats served as non-diabetic (non-DM). Diabetic rats were divided into two equal groups randomly; control and treatment. Six weeks later, a full-thickness circular excisional wound was created on the dorsum of each rat. AD-MSCs were injected intra-dermally around the wounds of treatment group. PBS was applied to control and non-DM groups. The wound area was measured every other day. After wound healing completion, full thickness skin samples were taken from the wound sites for evaluation of volume density of collagen fibers, length and volume density of vessels, and numerical density of fibroblasts by stereological methods.

Results

AD-MSCs accelerated wound healing rate in diabetic rats, but did not increase length and volume density of the vessels and volume density of the collagen fibers. AD-MSCs decreased the numerical density of fibroblasts.

Conclusions

We concluded that AD-MSCs enhances diabetic wound healing rate probably by other mechanisms rather than enhancing angiogenesis or accumulating collagen fibers.     

Color of culprit lesion at 6 months after plain old balloon angioplasty versus stenting in patients with acute myocardial infarction

Background

Although the healing process of disrupted yellow plaques at myocardial infarction (MI) culprit lesions has been reported, the effect of stenting on this process has not been clarified. Stenting has been reported to deteriorate the endothelial function after percutaneous coronary intervention (PCI). Therefore, we compared the angioscopic morphology of culprit lesions at 6 months after plain old balloon angioplasty (POBA) and stenting to clarify the effect of stenting on the healing of disrupted culprit plaques of acute MI.

Methods

Patients with acute MI who had yellow culprit plaque, successful reperfusion therapy with POBA (n = 21) or stenting (n = 22), and a successful 6-month follow-up angioscopic examination were included in this study. Oral ticlopidine (200mg/day) was administered for 3 to 6 months after stenting.

Results

At 6 months after reperfusion therapy, the color of the culprit lesion became white in significantly more patients treated with stenting than treated with POBA (50% vs 14%; P = .01). However, the prevalence of thrombus appeared to be higher in patients treated with stenting than in patients treated with POBA (27% vs 5%; P = .04). Although there was some difference in the patients' characteristics in the groups, logistic regression analysis revealed no significant influence of those factors on the color of or on the prevalence of thrombus at the culprit lesion.

Conclusions

Coronary stenting in patients with acute MI leads to the disappearance of yellow color at a significantly higher rate than POBA; however, whether it stabilizes the plaque requires further investigation.     

Nursing role in monitoring during cardiopulmonary resuscitation and in the peri-arrest period: a review

Objective

The study objective was to present a comprehensive literature review on the monitoring of patients with cardiac arrest (CA) and the nursing contribution in this crucial situation. Monitoring techniques during cardiopulmonary resuscitation and in the peri-arrest period (just before or after CA) are included.

Methods

Approaches used to access the research studies included a comprehensive search in relevant electronic databases (Medline, CINAHL, EMBASE, Cochrane Review, British Nursing Index) using relevant keywords (eg, cardiac arrest, resuscitation, monitoring, nurse, survival, outcome). Books and journals known to the authors were also used.

Results

The nurse’s role in patients with CA is extremely significant and if performed correctly adds great insight to treatment planning and correct management.

Conclusion

Early recognition of CA and invasive (methods and equipment that require endarterial or intravenous access) and noninvasive monitoring should be prompt and appropriate for early return of spontaneous circulation and improved neurologic outcome in patients.     

Comparison between a sustained administration of carvedilol versus atenolol to reduce restenosis after coronary stenting

Background

Carvedilol is a direct inhibitor of vascular smooth muscle cell migration and proliferation through inhibition of mitogen-activated protein kinase activity and regulation of cell cycle progression. It produced an 84% suppression of neointimal hyperplasia in rat carotid angioplasty model, but no data are available regarding its effect on stent restenosis in patients. We tested whether a sustained oral administration of carvedilol reduces restenosis after coronary stenting in patients.

Methods

One hundred fifty-nine patients were randomly assigned to receive either carvedilol (50 mg/d, n = 80) or atenolol (50 mg/d, n = 79) at least 1 day before stenting and continued on the same medication over a period of 3 months. The primary end point was angiographic restenosis (>50% diameter stenosis) at follow-up angiography.

Results

Baseline clinical and angiographic variables were similar between the carvedilol and atenolol group. The carvedilol dose was tolerable in most patients but reduced in 3 patients because of hypotension or dizziness. Angiographic follow-up was done in 137 patients (86%), and restenosis rate was not different significantly between both groups (17.1% versus 19.4%, P = .732).

Conclusions

A sustained oral administration of carvedilol is not effective to reduce restenosis after stenting in patients. With carvedilol targeting regulators of cell cycle progression and having a profound neointimal inhibition with a high blood concentration in an animal study, further investigations with a stent-based delivery to achieve a high local concentration may be warranted.     

Prevalence and risk factors for erectile dysfunction in the US

Purpose

To assess the prevalence of erectile dysfunction and to quantify associations between putative risk factors and erectile dysfunction in the US adult male population.

Methods

Cross-sectional analysis of data from 2126 adult male participants in the 2001-2002 National Health and Nutrition Examination Survey (NHANES). Erectile dysfunction assessed by a single question during a self-paced, computer-assisted self-interview. These data are nationally representative of the noninstitutionalized adult male population in the US.

Results

The overall prevalence of erectile dysfunction in men aged ≥20 years was 18.4% (95% confidence interval [CI], 16.2-20.7), suggesting that erectile dysfunction affects 18 million men (95% CI, 16-20) in the US. The prevalence of erectile dysfunction was highly positively related to age but was also particularly high among men with one or more cardiovascular risk factors, men with hypertension, and men with a history of cardiovascular disease, even after age adjustment. Among men with diabetes, the crude prevalence of erectile dysfunction was 51.3% (95% CI, 41.9-60.7). In multivariable analyses, erectile dysfunction was significantly and independently associated with diabetes, lower attained education, and lack of physical activity.

Conclusions

The high prevalence of erectile dysfunction among men with diabetes and hypertension suggests that screening for erectile dysfunction in these patients may be warranted. Physical activity and other measures for the prevention of cardiovascular disease and diabetes may prevent decrease in erectile function.     

Use of clopidogrel post-coronary artery bypass surgery in canadian patients with acute coronary syndromes

Background

Randomized trials have established the efficacy of clopidogrel in acute coronary syndromes (ACS). The benefit of clopidogrel has also been observed in the subgroup of ACS patients who subsequently undergo coronary artery bypass surgery (CABG); however, this therapy is discontinued preoperatively and the frequency with which clopidogrel is restarted post-CABG is unknown.

Methods

We examined the pattern of clopidogrel use in the Canadian Global Registry of Acute Coronary Events (GRACE), GRACE2, and CANRACE (2003-2008) post-CABG ACS patients. We stratified the patients according to whether they underwent CABG during their index hospitalization for ACS and whether they were prescribed clopidogrel at discharge.

Results

Among those patients in whom clopidogrel status at discharge was known, 5904 (60%) of 9841 were discharged from hospital on clopidogrel. Use of clopidogrel at discharge was observed in 2222 (40.8%) of 5443 patients who were medically managed (ie, did not undergo percutaneous coronary intervention [PCI] or CABG) and in 3585 (90.1%) of 3980 patients who underwent in-hospital PCI. Overall, 455 (3.3%) of 13,776 patients underwent CABG during the index hospitalization; 255 (56%) patients were started on clopidogrel during the first 24 hours, and 66 of these patients (25.9%) were discharged on clopidogrel. In contrast, 5681 (61.3%) of the 9262 patients who did not undergo in-hospital CABG were discharged on clopidogrel.

Conclusions

Although current guidelines recommend the use of clopidogrel post-CABG in patients with ACS, our observations suggest that only 1 in 4 or 5 Canadian patients are discharged on this therapy.     

Mid-term survival of patients undergoing major cardiac surgery

Introduction and objectives

Evaluating patient outcomes following cardiac surgery is a means of measuring the quality of that surgery. The present study analyzes survival and the risk factors associated with mid-term mortality of patients undergoing cardiac surgery in Son Dureta University Hospital (Palma, Balearic Islands, Spain).

Methods

From November 2002 thru December 2007, 1938 patients underwent interventions. Patients were stratified in 4 age groups. Of 1900 patients discharged from hospital, 1844 were followed until December 31, 2008. Following discharge, we constructed Kaplan-Meier survival curves and performed Cox regression analysis to determine which variables associated with mid-term mortality.

Results

In-hospital mortality of the 1,938 patients was 1.96% (CI 95%, 1.36%-2.6%). Survival probability at 1, 3 and 5 years follow-up was 98%, 94% and 90%, respectively. Mean follow-up was 3.2 (0.01-6.06) years. Patients aged ≥70 years showed a lower survival rate than those aged <70 (log rank test, P <.0001). At the end of follow-up, mortality was 6.5% (CI 95%, 5.4%-7.7%). Age ≥70 years, a history of severe ventricular dysfunction (ejection fraction <30%), severe pulmonary hypertension, diabetes mellitus, preoperative anemia, postoperative stroke, and hospital stay were independently associated with mid-term mortality.

Conclusions

Mid-term survival after discharge was highly satisfactory. Mid-term mortality varied with age and other pre- and postoperative factors.Full English text available from: www.revespcardiol.org     

The achievement of target cholesterol level differs between coronary heart disease and diabetic patients

Background

Guidelines recommend that LDL-C level should be < 100 mg/dl among diabetes mellitus (DM) and coronary heart disease (CHD) patients.

Objective

To evaluate how patients with DM and CHD differ in attaining the target level and to examine the association between goal achievement, demographic and clinical parameters.

Methods

The study was conducted in Maccabi Healthcare Services, the second largest health maintenance organization in Israel. All patients with DM (n = 54,261), CHD (n = 24,083) or DM and CHD (n = 15,370) who were listed in the computerized database and had at least one LDL-C level measurement between January 1, 2007 and July 15, 2008 were eligible. The percentage of patients who attained LDL-C level < 100 mg/dl and its association with demographic and clinical parameters were analyzed.

Results

The rate of reaching the LDL-C target level was higher among the CHD and CHD and DM patients than DM ones (67% vs. 57% vs. 50%, p < 0.001, respectively). Male gender; 5th socioeconomic status quintile; underlying disease i.e. CHD, CHD and DM; high statins compliance; and revascularization by percutaneous coronary intervention predicted for reaching target level. DM; absence of renal function evaluation; hospitalizations; HbA1C > 7% or missing its measurements had a negative predictive value.

Conclusions

The rate of reaching LDL-C target level should be increased in all high risk patients, mainly diabetic ones. Efforts should include educational programs to physicians and patients regarding the importance, the need to adhere and to intensify the cholesterol lowering treatment.     

IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030

Introduction

Diabetes is an increasingly important condition globally and robust estimates of its prevalence are required for allocating resources.

Methods

Data sources from 1980 to April 2011 were sought and characterised. The Analytic Hierarchy Process (AHP) was used to select the most appropriate study or studies for each country, and estimates for countries without data were modelled. A logistic regression model was used to generate smoothed age-specific estimates which were applied to UN population estimates for 2011.

Results

A total of 565 data sources were reviewed, of which 170 sources from 110 countries were selected. In 2011 there are 366 million people with diabetes, and this is expected to rise to 552 million by 2030. Most people with diabetes live in low- and middle-income countries, and these countries will also see the greatest increase over the next 19 years.

Discussion

This paper builds on previous IDF estimates and shows that the global diabetes epidemic continues to grow. Recent studies show that previous estimates have been very conservative. The new IDF estimates use a simple and transparent approach and are consistent with recent estimates from the Global Burden of Disease study. IDF estimates will be updated annually.     

Biofeedback treatment increases heart rate variability in patients with known coronary artery disease

Objectives

To determine if cardiorespiratory biofeedback increases heart rate variability (HRV) in patients with documented coronary artery disease (CAD).

Background

Diminished HRV has been associated with increased cardiac morbidity and mortality. Evidence suggests that various lifestyle changes and pharmacologic therapies can improve HRV. The objective of this study was to determine if biofeedback increases HRV in patients with CAD.

Methods

Patients with established CAD (n = 63; mean age, 67 years) were randomly assigned to conventional therapy or to 6 biofeedback sessions consisting of abdominal breath training, heart and respiratory physiologic feedback, and daily breathing practice. HRV was measured by the standard deviation of normal-to-normal QRS complexes (SDNN) at week 1 (pretreatment), week 6 (after treatment), and week 18 (follow-up).

Results

Baseline characteristics were similar for the treatment and control groups. The SDNN for the biofeedback and control groups did not differ at baseline or at week 6 but were significantly different at week 18. The biofeedback group showed a significant increase in SDNN from baseline to week 6 (P < .001) and to week 18 (P = .003). The control subjects had no change from baseline to week 6 (P = .214) and week 18 (P = .27).

Conclusions

Biofeedback increases HRV in patients with CAD and therefore may be an integral tool for improving cardiac morbidity and mortality rates.     

Risk factors for "major" embolic events in hospitalized patients with infective endocarditis

Background

Infective endocarditis often is complicated by embolic events after hospital admission. Identifying patients at higher risk may improve the disease outcome. This study was aimed at identifying predictors of embolic risk among the clinical and laboratory data obtained on hospital admission in patients diagnosed as having definite infective endocarditis according to the Duke criteria.

Methods

Ninety-four patients were enrolled in a prospective study. The results of hematologic, echocardiographic, and microbiological investigations were analyzed, using statistical methods as appropriate. Multivariate analysis was applied to variables significantly associated with embolism in univariate analysis.

Results

Forty-six percent of patients had a major embolic complication after admission. No association was found between embolism and sex, site of infection, or microorganism involved. Patients with embolism were significantly younger, had larger vegetation, and showed a significantly higher level of serum C-reactive protein and lower albumin concentrations than those without embolism. Young age, larger vegetation size, and high levels of C-reactive protein were the independent variables associated with an increased incidence of embolic events in the multivariate logistic regression analysis.

Conclusions

Our data indicate that patients with infective endocarditis with young age and/or with large vegetation and/or with high serum levels of C-reactive protein are at increased risk of major embolic complications during the in-hospital course of the disease.