Comparative effectiveness of novel oral anticoagulants for atrial fibrillation: evidence from pair-wise and warfarin-controlled network meta-analyses.

INTRODUCTION: Novel oral anticoagulants have been tested against warfarin for atrial fibrillation, yet no direct comparison is available. We thus aimed to perform pair-wise (direct) and warfarin-adjusted network (i.e. indirect) meta-analyses of novel oral anticoagulants for atrial fibrillation. METHODS: Databases were searched for randomized warfarin-controlled trials of novel anticoagulants for non-valvular atrial fibrillation. The primary end-point was long-term stroke/systemic embolism. Odds ratios (95% intervals) were computed with RevMan and WinBUGS. RESULTS: Seven trials (52701 patients) were included, focusing on apixaban, dabigatran, edoxaban and rivaroxaban. Pair-wise meta-analysis showed that after a weighted average of 23 months these novel anticoagulants lead to significant reductions in the risk of stroke/systemic embolism (odds ratio=0.81 [0.71-0.92], I2=23%) and all cause death (odds ratio=0.88 [0.82-0.95], I2=0%) in comparison to warfarin. Network meta-analysis showed that apixaban and dabigatran proved similarly superior to warfarin in preventing stroke/systemic embolism (odds ratio=0.78 [0.62-0.96] for apixaban vs warfarin; odds ratio=0.66 [0.52-0.84] for high-dose dabigatran vs warfarin; odds ratio for apixaban vs high-dose dabigatran=1.17 [0.85-1.63]), but apixaban was associated with fewer major bleedings (odds ratio=0.73 [0.57-0.93]) and drug discontinuations (odds ratio=0.64 [0.52-0.78]) than dabigatran. Rivaroxaban did not reduce stroke/systemic embolism (odds ratio=0.87 [0.71-1.07]) or major bleedings in comparison to warfarin (odds ratio=0.87 [0.71-1.07]) and was associated with more major bleedings in comparison to apixaban (odds ratio=1.52 [1.19-1.92]). Data for edoxaban were inconclusive. CONCLUSIONS: Novel oral anticoagulants appear as a very promising treatment option for atrial fibrillation.

Carotid plaque characterisation by IVUS-VH during carotid stenting: the "eyes wide shut" between plaque morphology and symptoms.

Stroke is the third most common cause of death in North America and ever year approximately 700,000 new strokes are reported in the United States. Seventy-five percent of these occur in the distribution of the carotid arteries. Among strokes of a thromboembolic etiology, carotid occlusive disease is the most common cause. As many as 150,300 stroke-related fatalities are documented annually, with a total cost for the health-care system of approximately $ 18 billion per year. This review will focus on the different pathomorphologic aspects of carotid plaque, outlining the similarities and differences with the coronary plaque, with particular attention on how intravascular imaging may contribute to a better stratification of the patient treatment.

The rough guide to systematic reviews and meta-analyses.

The hierarchy of evidence based medicine postulates that systematic reviews of homogenous randomized trials represent one of the uppermost levels of clinical evidence. Indeed, the current overwhelming role of systematic reviews, meta-analyses and meta-regression analyses in evidence based heath care calls for a thorough knowledge of the pros and cons of these study designs, even for the busy clinician. Despite this sore need, few succinct but thorough resources are available to guide users or would-be authors of systematic reviews. This article provides a rough guide to reading and, summarily, designing and conducting systematic reviews and meta-analyses.

Use of the LUCAS mechanical chest compression device for percutaneous coronary intervention during cardiac arrest: is it really a game changer?

Cardiopulmonary support including closed chest compression is a mainstay in the management of cardiac arrest. However, traditional means (i.e. manual) chest compression may be logistically challenging, especially in patients requiring emergent invasive procedures such as percutaneous coronary intervention for cardiac arrest due to acute myocardial infarction. The LUCAS mechanical chest compression device provides external and automated closed chest compression, thus enabling even complex invasive procedures without interrupting cardiopulmonary support. Nonetheless, no randomized trial has proved to date its benefit in comparison to standard manual chest compression, and to date only observational studies and consensus opinion support its clinical use.

Coronary artery disease: clinical presentation, diagnosis and prognosis in women.

Recent advances in the field of cardiovascular medicine have not led to significant declines in case-fatality rates for women as in men. There are gender-specific differences in symptoms profile, diagnosis and treatment of coronary disease in women. For women presenting for coronary heart disease (CHD) evaluation, traditional disease management approaches that focus on detection of a 'critical stenosis' often fail to identify those women critically at-risk. Symptoms do not help physicians in differential diagnosis of chest pain in women; indeed the most common presentation of obstructive CHD in women is atypical symptoms. In 50% of the cases, non-obstructive CHD at coronary angiography, due to 'noncardiac chest pain' or coronary microvascular dysfunction is frequently reported. For these reasons, the evidence reviewed suggests that prognostic risk assessment may work relatively better than diagnostic obstructive coronary disease assessment for women.

The management of pre-hypertension and metabolic syndrome.

The new guidelines for diagnosis and treatment of arterial hypertension introduce the new concept of "pre-hypertension", that comprises those individuals who have either systolic blood pressure (BP) of 120-139 mmHg or diastolic BP of 80-89 mmHg. The Committee recommended the identification of these individuals as they are at increased risk for progression to hypertension and subsequently other cardiovascular disease (CVD). Metabolic syndrome (MS) is a constellation of CVD risk factors, including atherogenic dyslipidemia, elevated BP, impaired glucose regulation, and abdominal obesity. Compared to those without MS, individuals with MS have a 61% increased risk of CVD. The aim of the review was explain the "real" relationship between these two clinical conditions describing the pathogenic mechanisms that put them in correlation. These findings may also offer compelling evidence for screening and early detection in vulnerable groups predisposed to CVD. Randomized intervention studies are needed to quantify the extent of any potential benefit of therapy among individuals with BP levels usually considered normal.

Paclitaxel eluting balloon: from bench to bedside.

Despite the impressive progress of percutaneous treatment modalities, restenosis remains the major Achilles heel of interventional cardiology. Approximately 25% of the general population treated for coronary diseases with a bare-metal stent and about 10% of patients treated with a drug-eluting stent develop an overgrowth of vascular tissue and renarrowing inside the stent, or in-stent restenosis. These rates are even greater in diabetics and patients at higher risk of restenosis both for clinical presentation (patients in dialysis, low ejection fraction) or anatomical characteristics (ostial, bifurcation, long lesions). Non-stent based local drug delivery and particularly the use of paclitaxel eluting balloon (PEB) could be one promising strategy to reduce restenosis. This review will briefly explore the different characteristics of PEB devices currently present in the market and summarize the results obtained both in animal models and clinical practice, giving an indication of the potential field of application of this new technology.

Chronic total coronary occlusion in patients with intermediate viability: value of low-dose dobutamine and contrast-enhanced 3-T MRI in predicting functional recovery in patients undergoing percutaneous revascularisation with drug-eluting stent.

PURPOSE: Myocardial viability was evaluated by magnetic resonance imaging (MRI) in patients with chronic total coronary occlusion (CTO) treated with a drug-eluting stent. Change in left ventricular ejection fraction (LVEF) was analysed. MATERIALS AND METHODS: Twenty-three patients with CTO underwent delayed-enhancement (DE) and low-dose dobutamine MRI (LD). Diastolic wall thickness (DWT), dobutamine-induced systolic wall thickening (SWT) and DE transmural extension were quantitatively assessed in vessel-related segments, calculating the contribution of viable tissue to SWT, expressed as viability index (VI)=[SWTx(100 - DE)]/100. Patients with transmural enhancement were excluded from revascularisation. At 6 months follow-up, patients underwent coronary angiography (CA) and MRI. Functional recovery was defined as a 2-mm increase in SWT. RESULTS: Transmural enhancement (mean DE 62.88+/-37.18] was present in three patients. Mean DWT, SWT, VI and DE of recanalised patients were 8.03+/-2.35, 2.64+/-1.56, 1.77+/-1.48 mm and 41.97+/-30.32. Revascularisation was successful in 14/16. Follow-up CA showed patency of treated vessels. Functional recovery was achieved in 13 patients. Functional recovery showed significant correlation with SWT (beta 1,779, p=0.015), and even higher correlation with VI (beta 2.032, p=0.011). LVEF improved significantly [Delta 95% confidence interval (CI) -4.47, p=0.0203). CONCLUSIONS: Invasive CTO treatment has beneficial effects on myocardial contractility that can be predicted by VI, and on LVEF.

Assessing coronary heart disease in women.

Coronary heart disease (CHD) is a leading cause of mortality in women worldwide. However CHD is still considered to be a male disease and it is likely to be under-diagnosed in women since symptoms are different in women and diagnostic tests may be less specific or sensitive. This review examines the symptoms and risk factors for CHD in women. The role of invasive and non-invasive tests together with their prognostic implications as well as indications for coronary revascularization will be discussed. New research should focus on the role of gender differences in CHD and trials specifically designed to study women.

Perioperative red blood cell transfusion and outcome in stable patients after elective major vascular surgery.

OBJECTIVES: Definitive evidence that red blood cell transfusion improves outcome after vascular surgery is lacking. The aims of the study were to determine, among stable consecutive patients who underwent elective major vascular surgery, (1) the association between postoperative transfusion and 30-day death, myocardial infarction, and both, and (2) and if this association differs according to the presence of postoperative anaemia (haemoglobin value less than 9.0 g/dL within 7 days after surgery). METHODS: A retrospective observational study was conducted on 359 patients prospectively screened according to the ACC/AHA guidelines for preoperative risk in non-cardiac surgery. Main outcome was 30-day death; secondary outcomes 30-day myocardial infarction, and composite of 30-day myocardial infarction or death. RESULTS: Of the patients included, 95 (26.5%) received at least one unit of red blood cells. Patients who received transfusion had a significantly increased hazard of 30-day death (hazard ratio [HR] 11.72, 95% confidence interval [CI] 3.92-35.10; p<0.0001), myocardial infarction (HR 3.3, 95% CI 1.7-6.1; p=0.0003), and both (HR 4.0 95% CI 2.2-7.3; p<0.0001). Such associations held even after adjusting for baseline characteristics, surgical risk, bleeding, and propensity to receive transfusion. There was a significant interaction between transfusion and postoperative anaemia (p=0.012). In patients without anaemia, transfusion was associated with higher risk of 30-day death (HR 19.20, 95% CI 3.99-92.45; p=0.007), myocardial infarction (HR 5.05, 95% CI 2.23-11.44; p=0.0001), and both. Conversely, in patients with anaemia this association was not significant. CONCLUSIONS: In patients who underwent elective major vascular surgery, perioperative transfusion was associated with a significantly increased risk of 30-day events which was more attributable to patients with lesser degree of anaemia. Our data caution against the use of liberal transfusion in stable vascular surgery patients.

Cardiovascular risk and prostanoids in systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by Raynaud's phenomenon and frequent cutaneous ulcers. In patients resistant to oral treatments, i.v. prostanoids are usefully employed. Some anecdotal reports underlined the potential risk to develop cardiovascular ischemic complications in prostanoid-treated SSc patients. METHODS: Fifty SSc patients (group 1: 44 female and 6 male, mean age 60.4 +/- 13.8SD) undergoing long-term prostanoid therapy (iloprost or alprostadil) and 42 control patients (group 2), treated with only oral drugs, were retrospectively evaluated for the cardiovascular risk and incidence of ischemic events. RESULTS: Ischemic cardiovascular complications, i.e., myocardial infarction or stroke, were recorded in a significantly higher number of patients undergoing prostanoid treatment compared to controls (group 1: 7/50, 14% vs. group 2: 1/42, 2.4%; p=0.041). Interestingly, these events were significantly more frequent in the subgroup of patients with high cardiovascular risk (group 1: 6/10, 60% vs. group 2: 1/19, 5.2%; p=0.0026). CONCLUSION: The present study suggests a possible role of prostanoid treatment in the pathogenesis of ischemic cardiovascular complications in SSc patients non-responders to oral vasodilators and high cardiovascular risk. Since prostanoids represent the first choice treatment of the most severe scleroderma ischemic cutaneous lesions, cardiovascular risk should be carefully evaluated in all patients before therapy.

3-Tesla MRI for the evaluation of myocardial viability: a comparative study with 1.5-Tesla MRI.

PURPOSE: We compared 3-Tesla (3-T) and 1.5-Tesla (1.5-T) cardiac magnetic resonance imaging (MRI) for the assessment of myocardial viability in nearly identical experimental conditions. MATERIALS AND METHODS: Thirty-five patients (mean age 63+/-11; 94.2% men) submitted to primary coronary angioplasty underwent both 3-T and 1.5-T cardiac MRI, which was considered the gold standard. Comparison was performed on the basis of the same viability imaging protocol, which included resting cine-MR [balanced fast-field echo (B-FFE) sequence] followed by contrast-enhanced MR to evaluate perfusion and delayed enhancement (DE). We then performed functional index measurements and visual estimation of kinesis, perfusion and DE referring to a 5-point scale. Image quality was assessed on the basis of signal to noise ratio (SNR) and contrast to noise ratio (CNR). RESULTS: We found nonsignificant differences between the two scanners (P=NS) in measuring the functional and viability parameters. Myocardial SNR was significantly higher with 3-T MRI compared with 1.5-T MRI (61.3% gain). Even though a loss of CNR was recorded in B-FFE and in first-pass perfusion sequences (12.4% and 23.7%, respectively), on DE images, we quantified the increase of SNR and CNR of infarction of 387.8% and 330%, respectively. CONCLUSIONS: We found that 3-T MRI showed high concordance with 1.5-T MRI in the evaluation of functional and viability parameters and provided better evidence of damaged myocardium.

Anti- and pro-oxidant factors and endothelial dysfunction in chronic cigarette smokers with coronary heart disease.

BACKGROUND: Endothelial dysfunction in cigarette smokers has been ascribed to increased oxidative damage. The aims of the present study were to compare the endothelial function of normotensive smokers with that of non-smokers and to examine its relation to some parameters representative of oxidative damage and of antioxidant capacity. METHODS: We investigated 32 chronic smokers (15-30 cigarettes daily) affected by coronary heart disease, ranging from acute myocardial infarction to instable angina pectoris, and 28 matched non-smokers without any definite risk factors. All subjects underwent assessment of nitric oxide (NO)-dependent endothelial function, measured as brachial artery vasodilatation in response to reactive ischemia, using a standardized echographic method. Plasma and urinary levels of NO were also measured in all subjects, as were urinary 15-isoprostane F(2t), plasma serum lipids, homocysteine (Hcy), ascorbic acid, retinol, tocopherol, and alpha- and beta-carotene (by high-performance liquid chromatography). RESULTS: Smokers showed a significantly lower NO-mediated vasodilatation response (3.50% vs. 6.18%, p<0.001) and higher levels of urinary NO metabolites and 15-isoprostane F(2t). They also had higher levels of Hcy (p<0.001); these values were significantly and inversely related to NO serum levels (r=-0.512, p<0.001). Moreover, smokers had a significant and corresponding reduction in circulating levels of ascorbic acid, tocopherol, and alpha- and beta-carotene. CONCLUSIONS: The present study shows a clear relation between endothelial dysfunction (NO production impairment) and cigarette smoking, especially in the presence of high levels of LDL-cholesterol. It also defines some markers of both oxidative damage and antioxidant protective capacity in this condition. The monitoring of these factors may be advisable in order to assess the amount of endothelial damage.

Coronary calcification in cardiovascular risk stratification.

The correlation between coronary calcifications and subclinical atherosclerotic disease has been well known for some years now. Today we are able to quantify coronary calcium deposits, the calcium score, by means of new imaging techniques such as electron beam computed tomography and multislice spiral computed tomography. A large number of studies performed using these methods has confirmed the association between coronary calcifications and atherosclerotic disease and has opened up the possibility of early diagnosis of any subclinical atherosclerotic disease in various subpopulations such as diabetics and nephropatics. The etiopathogenesis of coronary calcium has not yet been made clear; it appears to be an active process similar to bone formation that involves cells similar to those involved in the reabsorption of bone matrix. The calcium score, therefore, provides physicians with a further diagnostic tool able to better determine cardiovascular risk patients and supplements the Framingham risk score. International guidelines have not yet illustrated with any precision in which ambits to apply screening for the quantification of coronary calcium and consequently, for the time being, the use of such methods must be restricted to cases in which the possibility of any benefit can be scientifically shown. This review represents the state of the art on coronary calcification and its role in clinical practice.

Menopause and cardiovascular risk.

Menopause is not a disease, but a physiologic phase of a woman's life, due to the changes of their hormonal status. Fastidious symptoms may be associated with changes in the metabolism together with new cardiovascular risk factors, particularly aggressive for the female cardiovascular system, unprepared because of the protection due to the fertile period. Changes of the lipid profile, obesity, hypertension, glucose intolerance and diabetes mellitus may intervene as severe risk factors. Cardiovascular disease represents therefore the most frequent cause of mortality and morbidity also in the female gender more than cancer either in the United States as in Europe. The risks related to post-menopause are mainly due to the abrupt interruption of estrogen, which has indirect protective effects on lipid, glycidic metabolism and direct effects on vessel function. They have, in fact, vasodilator action due to nitric oxide release, calcium-antagonist like action and an antiproliferative effect on smooth muscle cells. Post-menopause is also frequently associated with hypertension, the most frequent related factor to coronary artery disease. Hypertension is due to increased body mass index, with insulin-resistance, sodium retention, increased blood viscosity and estrogen deficiency with increased smooth muscle cell proliferation which determines an increase in systemic vascular resistance. Age and estrogen deficiency are together the most important cause of cardiovascular risk in post-menopause. The discovery of alpha and recently beta estrogen receptors on coronary female vessels unaffected by atherosclerosis either during pre and post-menopause phase are possible key of interpretation of pathophysiology of coronary artery disease in women, with important therapeutic consequence.

Aldosterone inhibition limits collagen synthesis and progressive left ventricular enlargement after anterior myocardial infarction.

BACKGROUND: The reparative process after myocardial infarction is related to active collagen synthesis. Previous experimental studies demonstrated that cardiac fibrosis is mediated by angiotensin II and aldosterone; this mechanism is not clearly confirmed in patients who have had a myocardial infarction. The aim of this study was to evaluate whether the suppression of aldosterone may be helpful in reducing postinfarction collagen synthesis (and progressive left ventricular dilation) in patients treated with an angiotensin-converting enzyme inhibitor for a recent myocardial infarction. METHODS: We enrolled 46 patients (ages 60+/-11 years, 34 males) with a first episode of anterior transmural thrombolized myocardial infarction. At hospital discharge patients were randomized to receive potassium canrenoate, an oral aldosterone inhibitor, 50 mg once daily (group 1, n = 24) or placebo (group 2, n = 22). All enrolled patients were on angiotensin-converting enzyme inhibitor therapy. The serum concentration of the aminoterminal propeptide of type III procollagen was used to measure the collagen synthesis rate; dosage was obtained before enrollment, at hospital discharge, and after 3, 6, and 12 months of follow-up. RESULTS: After 3, 6, and 12 months of treatment, the aminoterminal propeptide of type III procollagen serum levels was significantly higher in the placebo group compared with the aldosterone inhibitor group; after 6 and 12 months we observed significantly smaller left ventricular volumes in the active treatment group. CONCLUSION: Potassium canrenoate, combined with an angiotensin-converting enzyme inhibitor, may reduce postinfarction collagen synthesis and progressive left ventricular dilation.