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Justin A Ezekowitz

Publications and source records attributed to Justin A Ezekowitz.

11 recordsLinked to original sources

Racial outcomes in patients with diabetic cardiomyopathy treated with an aldose reductase inhibitor: the ARISE-HF trial.

BACKGROUND: Racial and ethnic differences in diabetic cardiomyopathy (DbCM) exist, with black and Hispanic participants showing poorer health status. It remains unclear whether these differences affect the natural progression of the disease. We aimed to evaluate disease progression in individuals with DbCM, as well as racial differences in the response to AT-001. METHODS: A total of 625 participants with DbCM were randomised to either placebo or AT-001 and followed for 15 months. The primary outcome was change in peak oxygen uptake (peak VO2) and secondary outcomes included Kansas City Cardiomyopathy Questionnaire (KCCQ) and Physical Activity Scale for the Elderly scores. Analyses were stratified by race and ethnicity (black, Hispanic, white). RESULTS: Black and Hispanic participants who received placebo experienced greater declines in peak VO2 (-0.74 and -1.67 mL/kg/min, respectively) compared with white participants (-0.23 mL/kg/min, p=0.005). AT-001 demonstrated a non-statistically significant trend towards slower declines in peak VO2 in black and Hispanic participants (-0.31 and -0.62 mL/kg/min, p=0.29, respectively). Black participants who received placebo had the largest declines in most KCCQ scores. CONCLUSION: Black and Hispanic participants with DbCM experienced faster disease progression, with black participants showing the most pronounced functional and quality of life declines. The effect of AT-001 on peak VO2 changes was not statistically significant with similar effects between racial and ethnic groups (NCT04083339). TRIAL REGISTRATION NUMBER: NCT04083339.

Aged↗

N-terminal pro-brain natriuretic peptide and the timing, extent and mortality in ST elevation myocardial infarction.

AIMS: While natriuretic peptides have demonstrated diagnostic and prognostic potential in cardiac disorders, little is known about their relationship with the onset and quantification of myocardial infarction. The relationship of serial N-terminal pro-brain natriuretic peptide (NT-proBNP) with duration from symptom onset, infarct size and prognosis in ST elevation myocardial infarction (STEMI) patients treated with primary percutaneous intervention was examined. METHODS AND RESULTS: Three hundred thirty-one STEMI patients in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial, which evaluated pexelizumab versus placebo, were studied. NT-proBNP (pg/mL) was measured at randomization, 24 h and 72 h; creatine kinase-MB area under the curve was measured at 72 h; and QRS score was assessed at discharge. Prognosis was ascertained from the 90-day composite clinical outcome of death, shock, stroke and congestive heart failure. Multivariate logistical regression was used to adjust for baseline characteristics for models at randomization, 24 h and 72 h. NT-proBNP was higher in patients with longer time from symptom onset (P<0.001) and correlated with measures of infarct size, including the area under the curve (P<0.001) and QRS score (P<0.001). Patients reaching the primary end point had markedly higher NT-proBNP at each sampling period (P<0.001). NT-proBNP at all time points was the strongest independent predictor of the primary end point in the multivariate model: in the 24 h model, only age and 24 h NT-proBNP (C-index 0.83); and only age, Killip class and NT-proBNP was in the 72 h model (C-index 0.85). CONCLUSIONS: Higher NT-proBNP at 24 h correlated with larger infarct size and worse clinical outcomes. NT-proBNP at baseline, 24 h and 72 h after presentation with acute STEMI, is an independent predictor of a poor outcome and adds clinically useful prognostic information.

Age Distribution↗

Angiotensin receptor blockers and risk of myocardial infarction: systematic review.

OBJECTIVE: To evaluate the effect of angiotensin receptor blockers on the risk of myocardial infarction in patients at risk for cardiovascular events. DESIGN: Systematic review of controlled trials of angiotensin receptor blockers. DATA SOURCES: Medline, Embase, Cochrane central register of controlled trials, hand search, and contact with investigators. SELECTION OF STUDIES: Predefined criteria were used to select controlled clinical trials comparing use of angiotensin receptor blockers with angiotensin converting enzyme (ACE) inhibitors or placebo in patients at risk for cardiovascular events. Data were extracted for patients' characteristics, interventions, quality of trials, and rates of myocardial infarction. RESULTS: 19 studies with 31,569 patients were included in the analysis. Two studies investigated the use of angiotensin receptor blockers in hypertensive patients, four studies in patients with diabetes and nephropathy, 10 studies in patients with heart failure, and three in patients with recent myocardial infarction or ischaemic syndrome. 11 studies of 21,062 patients allowed for comparison between angiotensin receptor blockers and placebo; nine studies of 10,625 patients allowed for comparison between angiotensin receptor blockers and ACE inhibitors. Use of angiotensin receptor blockers was not associated with increased risk of myocardial infarction compared with placebo (odds ratio 0.94, 95% confidence interval 0.75 to 1.16) nor with increased risk of myocardial infarction compared with ACE inhibitors (1.01, 0.87 to 1.16). CONCLUSIONS: Treatment with angiotensin receptor blockers was not associated with a significantly increased risk of myocardial infarction. The 95% confidence intervals do, however, not exclude an increase of up to 16% in the risk of myocardial infarction or a reduction in risk of up to 25%. Until further information specifically dealing with this issue is available from large prospective trials, our findings may alleviate recent concerns over the safety of this class of medications.

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Impact of specialist follow-up in outpatients with congestive heart failure.

BACKGROUND: There is uncertainty about whether physician specialty influences the outcomes of outpatients with congestive heart failure after adjustment for differences in case mix. Our objective was to determine the impact of physician specialty on outcomes in outpatients with new-onset congestive heart failure. METHODS: The study was a population-based retrospective cohort study involving patients with new-onset congestive heart failure discharged from 128 acute care hospitals in Alberta between Apr. 1, 1998, and July 1, 2000. Outcomes were resource utilization (clinic visits, emergency department visits and hospital admissions) and survival at 30 days and 1 year. RESULTS: A total of 3136 patients were discharged from hospital with a new diagnosis of congestive heart failure (median age 76 years, 50% men). Of these, 1062 (34%) received no follow-up visits for cardiovascular care, 738 (24%) were seen by a family physician (FP) alone, 29 (1%) by a specialist (cardiologist or general internist) alone and 1307 (42%) by both a specialist and an FP. Compared with patients who received no follow-up cardiovascular care, patients who received regular cardiovascular follow-up visits with a physician had fewer visits to the emergency department (38% v. 80%), fewer were admitted to hospital (13% v. 94%), and the adjusted 1-year mortality was lower (22% v. 37%) (all p < 0.001). Compared with patients who received combined specialist and FP care, patients cared for exclusively by FPs had fewer outpatient visits (median 9 v. 17 in the first year), fewer of these patients presented to the emergency department (24% v. 45% in the first year), and fewer were readmitted for cardiovascular care (7% v. 16%) (all p < 0.001). However, the adjusted mortality at 1 year was lower among patients treated with combined care (17% v. 28%, p < 0.001) despite a higher burden of comorbidities. In a multivariate model adjusting for comorbidities (with no cardiovascular follow-up visits as the reference category), the mortality was lower among patients followed on an outpatient basis by an FP alone (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.53-0.82) or by an FP and a specialist (OR 0.34, 95% CI 0.28-0.42). In a proportional hazards model with time-dependent covariates (with adjustment for frequency of follow-up visits), the risk of all-cause mortality was reduced significantly (hazard ratio 0.98, 95% CI 0.97- 0.99) with each specialist visit compared with FP care alone. INTERPRETATION: Patients with congestive heart failure followed by both specialists and FPs had significantly better survival than those followed by FPs alone (or those who received no specific cardiovascular follow-up care). Methods to improve timely and appropriate access to specialists and to improve collaborative care structures are needed.

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The interaction among sex, hemoglobin and outcomes in a specialty heart failure clinic.

PURPOSE: Although anemia has recently been demonstrated to be a marker for poor outcomes in patients with congestive heart failure (CHF), the impact of sex on the prevalence and prognostic impact of anemia has not been adequately explored. Accordingly, the relationship among sex, anemia and outcomes in CHF was analyzed. SUBJECTS: Patients seen at a specialty CHF clinic from 1989 to 2001. METHODS: A retrospective analysis of prospectively collected data was performed using chi2 and Student's t tests to determine the association between anemia and mortality. Multivariate Cox proportional hazards models were used to measure the independent association of anemia with mortality in men and women. The World Health Organization definition of anemia (less than 130 g/L for men; less than 120 g/L for women) and the Centers for Disease Control and Prevention definition of anemia (less than 135 g/L for men, less than 120 g/L for women) were used, and hemoglobin was assessed as a continuous variable. RESULTS: There were 791 patients with CHF seen over a 12-year period (median age 69 years, median hemoglobin of 131 g/L [interquartile range 119 to 144 g/L]) and 34% were women. The demographics and treatments were similar for men and women, except that women were older (69 years versus 65 years, P<0.001), more likely to have a nonischemic etiology of CHF (P<0.001) or diastolic dysfunction (P<0.001), and lower creatinine clearances (P<0.001). Forty per cent of men and 35% of women were anemic using the World Health Organization definition. Anemia was associated with a one-year and five-year excess mortality in men (adjusted OR 1.7 [1.1 to 2.5] and 1.76 [1.2 to 2.7], respectively), but this was not observed in women (adjusted OR 1.2 [0.7 to 2.2] and 1.2 [0.7 to 2.1], respectively). CONCLUSIONS: Anemia is prevalent in heart failure and predicts mortality in men but not in women. Given this result, the authors recommend that randomized trials evaluating novel therapies for the correction of anemia in patients with heart failure should stratify their randomization by sex.

Age Distribution↗

Systematic review: cardiac resynchronization in patients with symptomatic heart failure.

BACKGROUND: Even with optimal pharmacotherapy, symptomatic heart failure is associated with substantial morbidity and mortality. PURPOSE: To determine the efficacy and safety of cardiac resynchronization therapy in adults with advanced systolic heart failure. DATA SOURCES: The Cochrane Central Register of Controlled Trials (2002, volume 4), MEDLINE (1980-2003), EMBASE (1980-2003), other electronic databases, and U.S. Food and Drug Administration reports. We contacted primary study authors and device manufacturers, and we hand searched bibliographies of relevant papers and conference proceedings. STUDY SELECTION: Randomized, controlled clinical trials for efficacy and controlled trials plus prospective cohort studies for safety. DATA EXTRACTION: Two reviewers chose studies and extracted data independently; random-effects models were used for analyses. DATA SYNTHESIS: Nine trials were included in the efficacy review (3216 patients). All trial participants had reduced ejection fraction and prolonged QRS duration, and 85% had New York Heart Association (NYHA) class III or IV symptoms. Cardiac resynchronization therapy improved ejection fraction (weighted mean difference, 0.035 [95% CI, 0.015 to 0.055]), quality of life (weighted mean reduction in score on the Minnesota Living with Heart Failure Questionnaire, 7.6 points [CI, 3.8 to 11.5 points]), and function (58% vs. 37% of patients improved by at least 1 NYHA class). Heart failure hospitalizations were reduced by 32% (relative risk [RR], 0.68 [CI, 0.41 to 1.12]), with benefits most marked in patients with NYHA class III or IV symptoms at baseline (RR, 0.65 [CI, 0.48 to 0.88]; number needed to treat for benefit [NNT(B)], 12). All-cause mortality was reduced by 21% (RR, 0.79 [CI, 0.66 to 0.96]; NNT(B), 24), driven largely by reductions in death from progressive heart failure (RR, 0.60 [CI, 0.36 to 1.01]). Eighteen studies (total of 3701 patients with cardiac resynchronization devices) were included in the safety review. Implant success rate was 90% (CI, 89% to 91%), and 0.4% of patients died during implantation (CI, 0.2% to 0.7%). Over a median 6-month follow-up, leads dislodged in 9% of patients (CI, 7% to 10%) and mechanical malfunctions occurred in 7% (CI, 5% to 8%). LIMITATIONS: These trials enrolled only patients with heart failure with NYHA class III or IV symptoms despite medical therapy, a prolonged QRS duration, and reduced ejection fraction; in addition, experienced providers implanted the devices. Because all but one of these trials randomly assigned patients after device implantation, their results may overestimate the potential benefits of cardiac resynchronization. Finally, since few patients in these trials had bradyarrhythmias or atrial fibrillation, the role of cardiac resynchronization in such patients is uncertain. CONCLUSIONS: In selected patients with heart failure, cardiac resynchronization therapy improves functional and hemodynamic status, reduces heart failure hospitalizations, and reduces all-cause mortality.

Cardiac Pacing, Artificial↗

Stroke: strategies for primary prevention.

Stroke is a leading cause of morbidity and mortality in North America. Primary prevention of stroke includes lifestyle modifications and measures to control blood pressure, cholesterol levels, diabetes mellitus, and atrial fibrillation. Lowering blood pressure in patients with hypertension prevents both hemorrhagic and ischemic stroke (relative risk reduction, 35 to 45 percent). Observational studies suggest that higher cholesterol levels are associated with an increased risk of ischemic stroke, and treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) may reduce the risk of fatal and nonfatal stroke by 25 percent. Although high-quality evidence linking tighter glucose control with stroke reduction is lacking, good glucose control and aggressive treatment of hypertension and hyperlipidemia in patients with diabetes mellitus are recommended. The risk of stroke in patients with atrial fibrillation and the role of anticoagulation depend on factors such as age and the presence of comorbid conditions. Controversy exists about the roles of angiotensin-converting enzyme inhibitors and aspirin in the primary prevention of stroke.

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Implantable cardioverter defibrillators in primary and secondary prevention: a systematic review of randomized, controlled trials.

BACKGROUND: Sudden cardiac death is common in persons with cardiovascular disease. PURPOSE: To assess the efficacy of implantable cardioverter defibrillators (ICDs) in persons at increased risk for sudden cardiac death. DATA SOURCES: MEDLINE (1980-2002), EMBASE (1980-2002), Cochrane Controlled Clinical Trial Registry (2002, Volume 3), other databases, and conference proceedings. Primary study authors and device manufacturers were contacted, and bibliographies of relevant papers were hand searched. STUDY SELECTION: Randomized, controlled clinical trials evaluating ICDs versus usual care were selected. DATA EXTRACTION: Two reviewers extracted data independently. DATA SYNTHESIS: Eight trials were included in the final analysis (4909 patients, 1154 deaths). Compared with usual care (most commonly amiodarone therapy), ICDs significantly reduced sudden cardiac death (relative risk [RR], 0.43 [95% CI, 0.35 to 0.53]) and all-cause mortality (RR, 0.74 [CI, 0.67 to 0.82]). The included trials were divided a priori into two categories: secondary prevention (involving patients resuscitated after cardiac arrest or unstable ventricular tachycardia or ventricular fibrillation [ n = 1963]) and primary prevention (involving patients at increased risk for sudden cardiac death but without documented cardiac arrest, ventricular fibrillation, or ventricular tachycardia [ n = 2946]). Regardless of baseline risk, ICDs were equally efficacious in preventing sudden cardiac death in both types of trials (RR, 0.50 [CI, 0.38 to 0.66] for secondary prevention vs. 0.37 [CI, 0.27 to 0.50] for primary prevention). However, the magnitude of benefit in total mortality varied within the primary prevention trials depending on baseline risk for sudden cardiac death. CONCLUSIONS: Implantable cardioverter defibrillators prevent sudden cardiac death regardless of baseline risk. However, their impact on total mortality is sensitive to baseline risk for arrhythmic death. Decisions about resource allocation for ICDs depend on accurate stratification of patients according to risk.

Arrhythmias, Cardiac↗

Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure.

BACKGROUND: Although previous work has suggested that anemia is associated with an increased mortality in selected patients with congestive heart failure (CHF), little is known about the prevalence and predictors of anemia, or whether anemia is an independent prognostic factor in unselected, community-based patients with CHF. METHODS AND RESULTS: We analyzed a population-based cohort of patients with new-onset CHF from a database of patients discharged from 138 acute-care hospitals in Alberta, Canada, between April 1993 and March 2001. Logistic regression, Kaplan-Meier survival analyses, and Cox proportional hazards model were used. Among the 12 065 patients with CHF (median age 78 years), 17% had anemia, 58% of whom had anemia of chronic disease. After adjustment for clinical and demographic variables, patients with anemia were more likely to be older (odds ratio [OR] 1.01 per year) and female (OR 1.2 [95% confidence interval 1.1 to 1.3]) and to have a history of chronic renal insufficiency (OR=3.2 [95% confidence interval 2.8 to 3.6]), or hypertension (OR 1.3 [95% confidence interval 1.2 to 1.5]). Hazard ratios for mortality, adjusting for covariates, were 1.34 (1.24 to 1.46) in anemic patients, and 1.36 (1.23 to 1.50) in those patients with anemia of chronic disease. CONCLUSIONS: In this large cohort of community-dwelling patients with CHF, anemia is common and an independent prognostic factor for mortality. Further research into the mechanisms of anemia in CHF and randomized controlled trials to test whether correction of anemia improves prognosis in CHF are needed.

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