Antiarrhythmic agents have modest efficacy in preventing atrial fibrillation (AF) recurrence. Although retrospective analyses have suggested a preventive effect of inhibitors of the renin-angiotensin system (RAS) on AF development in patients with congestive heart failure or hypertension, the value of these agents has not been evaluated in patients with AF but without a high prevalence of hypertension or heart failure.
A retrospective analysis of the Canadian Trial of Atrial Fibrillation (CTAF) was conducted. CTAF demonstrated the superiority of amiodarone (A) over sotalol or propafenone (SP) in maintaining sinus rhythm in patients with AF. Of the 403 patients randomly assigned in CTAF, 11.7% of the A group and 12.7% of the SP group were receiving a RAS inhibitor at baseline. By multivariate analysis (including all the risk factors known to be associated with AF available in the database), the use of RAS blockers in addition to antiarrhythmic agents was not associated with additional benefit against AF development. There was a recurrence of AF in 59 patients (38.3%) and 14 patients (29.8%) of groups A and A-RAS, respectively, while 93 patients (61.6%) and 32 patients (62.8%) of the SP and SP-RAS groups, respectively, experienced recurrent AF.
Blocking the RAS did not provide additional benefit against AF recurrence in CTAF patients treated with an antiarrhythmic drug. These results underscore the need for randomized clinical trials to clearly define the role of RAS inhibitors in treating AF.
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Ischemic heart disease (IHD) is the most common cause of heart failure (HF); however, the role of revascularization in these patients is still unclear. Consensus on proper use of cardiac imaging to help determine which candidates should be considered for revascularization has been hindered by the absence of clinical studies that objectively and prospectively compare the prognostic information of each test obtained using both standard and advanced imaging.
This paper describes the design and methods to be used in the Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) multi-center trial. The primary objective is to compare the effect of HF imaging strategies on the composite clinical endpoint of cardiac death, myocardial infarction (MI), cardiac arrest and re-hospitalization for cardiac causes.In AIMI-HF, patients with HF of ischemic etiology (n = 1,261) will follow HF imaging strategy algorithms according to the question(s) asked by the physicians (for example, Is there ischemia and/or viability?), in agreement with local practices. Patients will be randomized to either standard (SPECT, Single photon emission computed tomography) imaging modalities for ischemia and/or viability or advanced imaging modalities: cardiac magnetic resonance imaging (CMR) or positron emission tomography (PET). In addition, eligible and consenting patients who could not be randomized, but were allocated to standard or advanced imaging based on clinical decisions, will be included in a registry.
AIMI-HF will be the largest randomized trial evaluating the role of standard and advanced imaging modalities in the management of ischemic cardiomyopathy and heart failure. This trial will complement the results of the Surgical Treatment for Ischemic Heart Failure (STICH) viability substudy and the PET and Recovery Following Revascularization (PARR-2) trial. The results will provide policy makers with data to support (or not) further investment in and wider dissemination of alternative 'advanced' imaging technologies.
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Recent Canadian lipid guidelines recommend that all high-risk patients receive medication to reduce low density lipoprotein cholesterol (LDL-C) below 2.5 mmol/L. The recently published Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) studies compared strategies of cholesterol lowering with atorvastatin 80 mg versus pravastatin 40 mg. Atorvastatin halted the progression of atherosclerosis (whereas atherosclerosis progressed in the patients receiving pravastatin), and resulted in a 16% reduction in the primary composite end point (all-cause death, myocardial infarction, unstable angina, revascularization and stroke) compared with the pravastatin-treated group. In the PROVE IT trial, LDL-C was reduced by atorvastatin to 1.6 mmol/L and by pravastatin to 2.46 mmol/L. Although lower LDL-C levels are one explanation for the improved outcomes with atorvastatin, pleiotropic differences of the two statins, such as their effects on inflammation and coagulation, cannot be excluded. Until trials are completed that compare outcomes from LDL-C lowering to different targets with the same statin, it is premature to recommend changes to the current Canadian guidelines. However, future recommendations may suggest much lower LDL-C targets than those currently recommended.
Atherosclerosis exacts a large toll on society in the form of cardiovascular morbidity, mortality, and resource use and is exacerbated by the epidemics of obesity and diabetes. Consequently, there is a critical need for more-effective methods of diagnosis, treatment, and prevention of the complications of atherosclerosis. Careful and well-conducted large population studies are needed in order to truly understand the natural history of the disease, its imaging biomarkers, and their links to patient outcomes. The Canadian Atherosclerosis Imaging Network (CAIN) is a unique research network funded by the Canadian Institutes of Health Research and the Canada Foundation for Innovation and designed to address these needs and to enable large population-based imaging studies. The central objective of CAIN is to move innovations in imaging toward their broad application in clinical research and clinical practice for the improved evaluation of cardiac and neurologic vascular disease. CAIN is established as an international resource for studying the natural history, progression, and regression of atherosclerosis, as well as novel therapeutic interventions aimed at atherosclerosis. The network represents Canada's leading atherosclerosis imaging experts, embodying both basic imaging science and clinical imaging research. The network is improving methods of detection and treatment of atherosclerosis and, through a better understanding of the underlying disease itself, improving strategies for disease prevention. The benefits are expected to appear in the next 2 to 3 years. CAIN will drive innovation in imaging technology within the field of cardiology and neurology and improve health outcomes in Canada and worldwide.
Despite the availability of several acute coronary syndrome (ACS) prognostic risk scores, there is no appropriate score for early-risk stratification at the time of the first medical contact with patients with ACS. The primary objective of this study is to develop a simple risk score that can be used for early-risk stratification of patients with ACS.
We derived the risk score from the Acute Myocardial Infarction in Quebec and Canada ACS-1 registries and validated the risk score in 4 other large data sets of patients with ACS (Canada ACS-2 registry, Canada-GRACE, EFFECT-1, and the FAST-MI registries). The final risk score is named the Canada Acute Coronary Syndrome Risk Score (C-ACS) and ranged from 0 to 4, with 1 point assigned for the presence of each of these variables: age =75 years, Killip >1, systolic blood pressure 100 beats/min. The primary end points were short-term (inhospital or 30-day) and long-term (1- or 5-year) all-cause mortality.
The C-ACS has good predictive values for short- and long-term mortality of patients with ST-segment elevation myocardial infarction and non-ST-segment elevation ACS. The negative predictive value of a C-ACS score =1 is excellent at =98% (95% CI 0.97-0.99) for short-term mortality and =93% (95% CI 0.91-0.96) for long-term mortality. In other words, a C-ACS score of 0 can potentially identify correctly =97% short-term survivors and =91% long-term survivors.
The C-ACS risk score permits rapid stratification of patients with ACS. Because this risk score is simple and easy to memorize and calculate, it can be rapidly applied by health care professionals without advanced medical training.
Erratum In: Am Heart J. 2013 Sep;166(3):604Yan, Andrew [corrected to Yan, Andrew T]; Loughlin, Jennifer O [corrected to O'Loughlin, Jennifer]; Yan, Raymond [corrected to Yan, Raymond T]
The concepts of "cardiometabolic risk," "metabolic syndrome," and "risk stratification" overlap and relate to the atherogenic process and development of type 2 diabetes. There is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. With the objectives of clarifying these concepts and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group reviewed the evidence related to emerging cardiovascular risk factors and Canadian guideline recommendations in order to present a detailed analysis and consolidated approach to the identification and management of cardiometabolic risk. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider risk factors related to ethnicity in order to appropriately evaluate everyone in their diverse patient populations.
Previous Canadian high vascular risk registries have demonstrated suboptimal goal-directed reductions in cardiovascular risk factors and underutilization of guideline-recommended therapies in part because of physician underestimation of cardiovascular risk.
The Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY) registry enrolled 33,438 stable coronary artery disease patients in 45 countries. In Canada, supplemental information was obtained specifying reasons that patients were not taking guideline-recommended medications.
In Canada, 1232 patients (9 provinces, 110 physicians) were enrolled and in comparison with the rest of the world, there were several differences in cardiovascular risk factors and medical history; in addition, the Canadian cohort had undergone less percutaneous coronary intervention, but more coronary artery bypass grafting. Among the Canadian cohort, many still continue to smoke (13%) and many do not meet secondary prevention targets for waist circumference (54%), body mass index (81%), physical activity (71%), cholesterol (43%), and systolic blood pressure (20%). Nevertheless, the use of guideline-recommended cardiovascular therapy was high and >90% reported partial/full financial coverage for medications. The number of patients not receiving guideline-recommended therapies because of apparent underestimation of risk was particularly low for antiplatelet agents (2%), ß-blockers (11%), and lipid-lowering therapies (1%).
Canadian patients with stable coronary artery disease did not meet several guideline-recommended secondary prevention targets, despite high use of evidence-based therapy, extensive financial coverage for these medications, and low physician underestimation of risk. Additional work is needed to identify and address the remaining barriers to effective risk factor control.
Coronary artery bypass graft surgery remains associated with significant postoperative cardiovascular morbidity and mortality in high-risk patients. MC-1 (pyridoxal-5'-phosphate monohydrate) inhibits purinergic receptors and intracellular influx of Ca2+, thereby reducing cellular injury during experimental ischemia and reperfusion. The MEND-CABG trial tested the hypothesis that MC-1 reduces cardiovascular morbidity and mortality after coronary artery bypass graft.
In a phase 2, double-blinded, placebo-controlled study, 901 patients scheduled for coronary artery bypass graft surgery with cardiopulmonary bypass and at high risk for subsequent cardiac or neurologic complications were randomly assigned to receive oral MC-1 (250 mg or 750 mg/d once daily) or placebo beginning 3 to 10 hours prior to surgery and continued to postoperative day 30.
At 30 days, MC-1 250 mg (compared with placebo) reduced the composite of death, nonfatal cerebral infarction, and nonfatal myocardial infarction by 14.0% (P = .3124) with peak creatinine kinase-myocardial band > or =50 ng/mL (prespecified primary end point); 32.3% (P = .0349) with peak creatinine kinase-myocardial band > or =70 ng/mL; and 37.2% (P = .0283) with peak creatinine kinase-myocardial band > or =100 ng/mL. Myocardial infarctions with peak creatinine kinase-myocardial band> or =100 ng/mL were reduced by 47.2% in the MC-1 250-mg group versus placebo (P = .0083). Greater efficacy was demonstrated with 250 mg than with the 750-mg dose of MC-1.
In high-risk patients undergoing coronary artery bypass graft, treatment with MC-1 did not significantly affect the prespecified primary end point but was associated with a significant reduction in perioperative myocardial infarction with creatinine kinase-myocardial band > or =100 ng/mL. A larger, well-powered trial is needed to evaluate the cardioprotective effects of MC-1.
Atrial fibrillation (AF) is frequently encountered in patients with heart failure (HF) and is also a predictor of morbidity and mortality in this population. Recent experimental studies have shown electrical and structural atrial remodeling with increased fibrosis in animals with HF and have suggested a preventive effect of ACE inhibitors (ACEi) on the development of AF. To verify the hypothesis that ACEi prevent the development of AF in patients with HF, we conducted a retrospective analysis of the patients from the Montreal Heart Institute (MHI) included in the Studies Of Left Ventricular Dysfunction (SOLVD).
Clinical charts were reviewed and serial ECGs interpreted by a single cardiologist blinded to drug allocation. Patients with AF or flutter on the baseline ECG were excluded. Baseline characteristics were obtained from the SOLVD databases. The mean follow-up was 2.9+/-1.0 years. Of the 391 patients randomly assigned at MHI, 374 were in sinus rhythm at the time of random assignment, with 186 taking enalapril and 188 taking placebo. Baseline characteristics were similar in the two groups except for a higher incidence of previous myocardial infarction in the enalapril group. Fifty-five patients had AF during the follow-up: 10 (5.4%) in the enalapril group and 45 (24%) in the placebo group (P
Comment In: Circulation. 2004 Jan 20;109(2):e1114734513
From the Montreal Heart Institute, Montreal, Canada (B.J.A., M.-P.D., M.R.B., A.B.d.O.M., V.L., A.-E.K., D.R., É.R., J.-C.T.); Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Canada (B.J.A., M.-P.D., M.R.B., A.B.d.O.M., É.R., J.-C.T.); Beaulieu-Saucier Université de Montréal Pharmacogenomics Centre, Montreal, Canada (M.-P.D., J.-C.T.); Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec (S.G.-O., P.M., P.P., Y.B.) and Department of Molecular Medicine (Y.B.), Laval University, Québec, Canada; Cardiology Department, AP-HP, Bichat Hospital, Paris, France (D.M.-Z.); and INSERM U698, University Paris 7, Paris, France (D.M.-Z.).
Studies have shown that high-density lipoprotein (HDL)-raising compounds induce regression of aortic valve stenosis (AVS) in animal models. However, whether patients with AVS have an impaired HDL metabolism is unknown.
A total of 1435 single nucleotide polymorphisms in genes associated with HDL cholesterol levels (in or around GALNT2, LPL, ABCA1, APOA5, SCARB1, LIPC, CETP, LCAT, LIPG, APOC4, and PLTP) were genotyped in 382 patients with echocardiography-confirmed AVS (aortic jet velocity =2.5 m/s) and 401 controls. After control for multiple testing, none of the genetic variants showed a positive association with case/control status (adjusted P=0.05 for all single nucleotide polymorphisms tested). In a subsample of this cohort, HDL cholesterol levels, apolipoprotein AI levels, lecithin-cholesterol acyltransferase activity, pre-?-HDL, HDL size, and 4 parameters of cholesterol efflux capacity were measured in apolipoprotein B-depleted serum samples from 86 patients with and 86 patients without AVS. Cholesterol efflux capacity was measured using J774 macrophages with and without stimulation of ATP-binding cassette A-1 expression by cAMP, and HepG2 hepatocytes for scavenger receptor class B type 1-mediated efflux. None of these parameters were different between cases and controls. However, compared with patients without coronary artery disease, sera from patients with coronary artery disease had lower HDL cholesterol levels, scavenger receptor class B type 1-mediated efflux, and HDL size (P=0.003), independently of the presence or absence of AVS.
Results of the present study suggest that, based on HDL genetics and HDL functionality, HDL metabolism does not seem to predict the risk of AVS. Because of our limited sample size, additional studies are needed to confirm these findings.