Baki Billah

B-Type Natriuretic Peptide–Guided Heart Failure Therapy: A Meta-analysis

BACKGROUND The use of plasma levels of B-type natriuretic peptides (BNPs) to guide treatment of patients with chronic heart failure (HF) has been investigated in a number of randomized controlled trials (RCTs). However, the benefits of this treatment approach have been uncertain. We therefore performed a meta-analysis to examine the overall effect of BNP-guided drug therapy on cardiovascular outcomes in patients with chronic HF. METHODS We identified RCTs by systematic search of manuscripts, abstracts, and databases. Eligible RCTs were those that enrolled more than 20 patients and involved comparison of BNP-guided drug therapy vs usual clinical care of the patient with chronic HF in an outpatient setting. RESULTS Eight RCTs with a total of 1726 patients and with a mean duration of 16 months (range, 3-24 months) were included in the meta-analysis. Overall, there was a significantly lower risk of all-cause mortality (relative risk [RR], 0.76; 95% confidence interval [CI], 0.63-0.91; P = .003) in the BNP-guided therapy group compared with the control group. In the subgroup of patients younger than 75 years, all-cause mortality was also significantly lower in the BNP-guided group (RR, 0.52; 95% CI, 0.33-0.82; P = .005). However, there was no reduction in mortality with BNP-guided therapy in patients 75 years or older (RR, 0.94; 95% CI, 0.71-1.25; P = .70). The risk of all-cause hospitalization and survival free of any hospitalization was not significantly different between groups (RR, 0.82; 95% CI, 0.64-1.05; P = .12 and RR, 1.07; 95% CI, 0.85-1.34; P = .58, respectively). The additional percentage of patients achieving target doses of angiotensin-converting enzyme inhibitors and beta-blockers during the course of these trials averaged 21% and 22% in the BNP group and 11.7% and 12.5% in the control group, respectively. CONCLUSIONS B-type natriuretic peptide-guided therapy reduces all-cause mortality in patients with chronic HF compared with usual clinical care, especially in patients younger than 75 years. A component of this survival benefit may be due to increased use of agents proven to decrease mortality in chronic HF. However, there does not seem to be a reduction in all-cause hospitalization or an increase in survival free of hospitalization using this approach.

Analysis of randomized controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers.

Beta blockers improve cardiac function and prolong survival in patients with systolic chronic heart failure (CHF). However, the exact mechanisms underlying these benefits are uncertain. Specifically, it is unclear whether a close relation exists between heart rate (HR) reduction and clinical outcomes with these agents. This hypothesis was therefore tested within randomized controlled trials of beta blockers in systolic CHF. Left ventricular ejection fraction (LVEF) and HR values at baseline and study end were obtained from available beta-blocker randomized clinical trials. The relation between change in HR and all-cause mortality as well as the LVEF was determined using regression analysis. Thirty-five trials, which included 22,926 patients with a mean follow-up duration of 9.6 months, were analyzed for all-cause mortality, the LVEF, and HR. There was a close relation between all-cause annualized mortality rate and HR (adjusted R2 = 0.51, p = 0.004). A strong correlation between change in HR and change in LVEF (adjusted R2 = 0.48, p = 0.000) was also observed. When only trials with >100 patients were included, an even tighter correlation was seen (adjusted R2 = 0.60, p = 0.0004). In conclusion, these analyses indicate that a major contributor to the clinical benefits of beta-blocker therapy in systolic CHF may be the HR-lowering effect of these agents. Therefore, the magnitude of HR reduction may be more important than the achievement of target dose in beta-blocker treatment of systolic CHF.

Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomised controlled clinical trials

Background: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states, treatment of which may prevent or delay the onset of overt diabetes and thus potentially reduce major cardiovascular (CV) events. We therefore sought to determine whether interventions (including diet, exercise and pharmacological therapy), altered all-cause and cardiovascular related mortality in such subjects. Methods: We performed a meta-analysis of prospective, randomised controlled trials (RCTs) that were identified in the medical literature and databases. Trials were eligible for inclusion if they reported all-cause mortality rates (at a minimum), recruited approximately 100 patients and had a minimum follow-up of one year. Interventions were divided into pharmacological and non-pharmacological. Results: Ten RCTs that enrolled 23,152 patients met the above entry criteria. Trials ran for an average of 3.75 years. Diabetes was delayed or prevented by these interventions vs control (risk ratio 0.83, 95%CI 0.80–0.86). Non-drug approaches (n = 3495) were superior to drug-based approaches (n = 20,872) in diabetes prevention (0.52, 0.46–0.58 vs 0.70, 0.58–0.85, P < 0.05). There was no difference in risk of all-cause mortality in the intervention versus control group (0.96, 0.84–1.10) and no difference in CV death (1.04, 0.61–1.78). There was a non-significant trend towards reduction in fatal and non-fatal myocardial infarction (0.59, 0.23–1.50). Fatal and non-fatal stroke was borderline reduced (0.76, 0.58–0.99) with intervention versus control. Conclusions: Despite interventions being mostly successful in retarding progression to overt diabetes, this did not result in reductions in all-cause or cardiovascular mortality, or myocardial infarction, with the possible exception of stroke.

An alternative scoring system to predict risk for surgical site infection complicating coronary artery bypass graft surgery

OBJECTIVE To analyze the risk factors for surgical site infection (SSI) complicating coronary artery bypass graft (CABG) surgery and to create an alternative SSI risk score based on the results of multivariate analysis. METHODS A prospective cohort study involving inpatient and laboratory-based surveillance of patients who underwent CABG surgery over a 27-month period from January 1, 2003 through March 31, 2005. Data were obtained from 6 acute care hospitals in Victoria, Australia, that contributed surveillance data for SSI complicating CABG surgery to the Victorian Hospital Acquired Infection Surveillance System Coordinating Centre and the Australasian Society of Cardiac and Thoracic Surgeons, also in Victoria. RESULTS A total of 4,633 (93%) of the 4,987 patients who underwent CABG surgery during this period were matched in the 2 systems databases. There were 286 SSIs and 62 deep or organ space sternal SSIs (deep or organ space sternal SSI rate, 1.33%). Univariate analysis revealed that diabetes mellitus, body mass index (BMI) greater than 35, and receipt of blood transfusion were risk factors for all types of SSI complicating CABG surgery. Six multivariate analysis models were created to examine either preoperative factors alone or preoperative factors combined with operative factors. All models revealed diabetes and BMI of 30 or greater as risk factors for SSI complicating CABG surgery. A new preoperative scoring system was devised to predict sternal SSI, which assigned 1 point for diabetes, 1 point for BMI of 30 or greater but less than 35, and 2 points for BMI of 35 or greater. Each point in the scoring system represented approximately a doubling of risk of SSI. The new scoring system performed better than the National Nosocomial Infections Surveillance System (NNIS) risk index at predicting SSI. CONCLUSION A new weighted scoring system based on preoperative risk factors was created to predict sternal SSI risk following CABG surgery. The new scoring system outperformed the NNIS risk index. Future studies are needed to validate this scoring system.

Unmasking the Theta Method

The Theta method of forecasting performed particularly well in the M3-competition and is therefore of interest to forecast practitioners. The description of the method given by Assimakopoulos and Nikolopoulos (2000) involves several pages of algebraic manipulation and is difficult to comprehend. We show that the method can be expressed much more simply; furthermore we show that the forecasts obtained are equivalent to simple exponential smoothing with drift.

An Australian risk prediction model for 30-day mortality after isolated coronary artery bypass: The AusSCORE

OBJECTIVE Our objective was to identify risk factors associated with 30-day mortality after isolated coronary artery bypass grafting in the Australian context and to develop a preoperative model for 30-day mortality risk prediction. SUMMARY BACKGROUND DATA Preoperative risk associated with cardiac surgery can be ascertained through a variety of risk prediction models, none of which is specific to the Australian population. Recently, it was shown that the widely used EuroSCORE model validated poorly for an Australian cohort. Hence, a valid model is required to appropriately guide surgeons and patients in assessing preoperative risk. METHODS Data from the Australasian Society of Cardiac and Thoracic Surgeons database project was used. All patients undergoing isolated coronary artery bypass grafting between July 2001 and June 2005 were included for analysis. The data were divided into creation and validation sets. The data in the creation set was used to develop the model and then the model was validated in the validation set. Preoperative variables with a P value of less than .25 in chi(2) analysis were entered into multiple logistic regression analysis to develop a preoperative predictive model. Bootstrap and backward elimination methods were used to identify variables that are truly independent predictors of mortality, and 6 candidate models were identified. The Akaike Information Criteria (AIC) and prediction mean square error were used to select the final model (AusSCORE) from this group of candidate models. The AusSCORE model was then validated by average receiver operating characteristic, the P value for the Hosmer-Lemeshow goodness-of-fit test, and prediction mean square error obtained from n-fold validation. RESULTS Over the 4-year period, 11,823 patients underwent cardiac surgery, of whom 65.9% (7709) had isolated coronary bypass procedures. The 30-day mortality rate for this group was 1.74% (134/7709). Factors selected as independent predictors in the preoperative isolated coronary bypass AusSCORE model were as follows: age, New York Heart Association class, ejection fraction estimate, urgency of procedure, previous cardiac surgery, hypercholesterolemia (lipid-lowering treatment), peripheral vascular disease, and cardiogenic shock. The average area under the receiver operating characteristic was 0.834, the P value for the Hosmer-Lemeshow chi(2) test statistic was 0.2415, and the prediction mean square error was 0.01869. CONCLUSION We have developed a preoperative 30-day mortality risk prediction model for isolated coronary artery bypass grafting for the Australian cohort.

A preoperative risk prediction model for 30-day mortality following cardiac surgery in an Australian cohort

BACKGROUND Population-specific risk models are required to build consumer and provider confidence in clinical service delivery, particularly when the risks may be life-threatening. Cardiac surgery carries such risks. Currently, there is no model developed on the Australian cardiac surgery population and this article presents a novel risk prediction model for the Australian cohort with the aim to provide a guide for the surgeons and patients in assessing preoperative risk factors for cardiac surgery. AIMS This study aims to identify preoperative risk factors associated with 30-day mortality following cardiac surgery for an Australian population and to develop a preoperative model for risk prediction. METHODS All patients (23016) undergoing cardiac surgery between July 2001 and June 2008 recorded in the Australian Society of Cardiac and Thoracic Surgeons (ASCTS) database were included in this analysis. The data were divided randomly into model creation (13810, 60%) and model validation (9206, 40%) sets. The model was developed on the creation set and then validated on the validation set. The bootstrap sampling and automated variable selection methods were used to develop several candidate models. The final model was selected from this group of candidate models by using prediction mean square error (MSE) and Bayesian Information Criteria (BIC). Using a multifold validation, the average receiver operating characteristic (ROC), p-value for Hosmer-Lemeshow chi-squared test and MSE were obtained. Risk thresholds for low-, moderate- and high-risk patients were defined. The expected and observed mortality for various risk groups were compared. The multicollinearity and first-order interaction effect between clinically meaningful risk factors were investigated. RESULTS A total of 23016 patients underwent cardiac surgery and the 30-day mortality rate was 3.2% (728 patients). Independent predictors of mortality in the model were: age, sex, the New York Heart Association (NYHA) class, urgency of procedure, ejection fraction estimate, lipid-lowering treatment, preoperative dialysis, previous cardiac surgery, procedure type, inotropic medication, peripheral vascular disease and body mass index (BMI). The model had an average ROC 0.8223 (95% confidence interval (CI): 0.8118-0.8227), p-value 0.8883 (95% CI: 0.8765-0.90) and MSE 0.0251 (95% CI: 0.02515-0.02516). The validation set had observed mortality 3.0% (95% CI: 2.7-3.3%) and predicted mortality 2.9% (95% CI: 2.6-3.2%). The low-risk group (additive score 0-3) had 0.6% observed mortality (95% CI: 0.3-0.9%) and 0.5% predicted mortality (95% CI: 0.2-0.8%). The moderate-risk group (additive score 4-9) had 1.7% observed mortality (95% CI: 1.2-2.2%) and 1.4% predicted mortality (95% CI: 1.0-1.8%). The observed mortality for the high-risk group (additive score 9 plus) was 6.7% (95% CI: 5.8-7.6%) and the expected mortality was 6.7% (95% CI: 5.8-7.6%). CONCLUSION A preoperative risk prediction model for 30-day mortality was developed for the Australian cardiac surgery population.

Critical analysis of early and late outcomes after isolated coronary artery bypass surgery in elderly patients.

BACKGROUND The proportion of elderly (≥80 years) patients undergoing coronary artery bypass surgery (CABG) is increasing. METHODS A retrospective analysis of data, collected by the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program between June 2001 and December 2009 was performed. Isolated CABG was performed in 21,534 patients; of these, 1,664 (7.7%) were at least 80 years old (group 1). Patient characteristics, morbidity, and short-term mortality of these patients were compared with those aged less than 80 years (group 2). The long-term outcome of group 1 patients after CABG surgery was compared with an age and sex-matched Australian population. RESULTS Patients over 80 years old were more likely to be female (36.6% vs 17.3%, p < 0.001) and presented significantly more often with heart failure, hypertension, and triple-vessel disease (all p < 0.05). The 30-day mortality was higher in group 1 patients (4.2% vs 1.5%, p < 0.001). Group 1 patients also had an increased risk of complications, including prolonged (>24 hours) ventilation (14.2% vs 8.2%, p < 0.001), renal failure (7.3% vs 3.4%, p < 0.001), and mean intensive care unit stay (60.7 vs 42.5 hours, p < 0.001). The 5-year survival of elderly patients (73%) was comparable with the age-matched Australian population. Independent risk factors for 30-day mortality in group 1 patients included preoperative renal failure (p = 0.010), congestive heart failure (p = 0.014), and a nonelective procedure (p = 0.016). CONCLUSIONS Elderly patients who undergo isolated CABG have significantly lower perioperative risks than have been previously reported. The long-term survival of these patients is comparable with an age-adjusted population.

Extending the Boundaries of Cardiac Resynchronization Therapy: Efficacy in Atrial Fibrillation, New York Heart Association Class II, and Narrow QRS Heart Failure Patients

BACKGROUND Large-scale clinical trials have demonstrated the benefits of cardiac resynchronization therapy (CRT) in patients with New York Heart Association (NYHA) Class III/IV heart failure, systolic left ventricular dysfunction, and a wide QRS. However, additional patient groups may also benefit from CRT. METHODS AND RESULTS We meta-analyzed clinical benefits of CRT in heart failure patients with narrow QRS, atrial fibrillation (AF) and NYHA Class II symptoms. Thirteen trials of 2882 patients contributed to this meta-analysis. In the narrow versus wide QRS group comparison, no difference in benefit was observed for change in left ventricular ejection fraction (standardized mean difference [SMD] 0.30, 95% confidence interval [CI] -0.37 to 0.97) or left ventricular end systolic volume (SMD 0.30, 95% CI -1.14 to 1.74). The benefit was greater in the wide QRS group for the 6-minute walk test (SMD 1.27, 95% CI 0.59 to 1.96) and NYHA class improvement (SMD 1.24, 95% CI 0.72 to 1.75). In the atrial fibrillation (AF) versus sinus rhythm (SR) group comparison, no difference in benefit was observed for change in left ventricular ejection fraction (SMD -0.38, 95% CI -1.28 to 0.53) or NYHA improvement (SMD 0.32, 95% CI -0.77 to 1.40). In the NYHA II versus NYHA III/IV group comparison, no difference in benefit was observed for change in left ventricular end diastolic diameter (SMD 0.05, 95% CI -0.94 to 1.05) or left ventricular end systolic diameter (SMD 0.74, 95% CI -1.98 to 3.46). CONCLUSIONS Large-scale clinical outcome trials of CRT are warranted in heart failure patients with narrow QRS, AF, and NYHA II, given the similar benefits observed to those with wide QRS, SR, and NYHA III/IV for many parameters.

Investigation of an outbreak of Serratia marcescens in a neonatal unit via a case-control study and molecular typing

BACKGROUND In March 2004, infection or colonization with Serratia marcescens affected one third of all neonates in a newborn services unit (NBS). METHODS We performed a case-control study and automated ribotyping. RESULTS Forty-nine cases were compared with 64 controls. The overall mean length of stay (LOS) in the NBS was 67 days for cases and 36 days for controls, P = .005. Cases were of lower mean birth weight than controls (1566 g vs 1968 g, respectively, P = .02). Risk factors that trended toward significance for S marcescens acquisition included the following: premature rupture of membranes (odds ratio [OR], 2.7; 95% confidence interval [95% CI]: 1.0-7.1; P = .05), vaginal delivery at our hospital (OR, 2.1; 95% CI: 0.9-4.6; P = .06), intubation at delivery (OR, 2.3; 95% CI: 0.9-5.2; P = .05), mechanical ventilation (OR, 2.1; 95% CI: 0.9-4.4; P = .06), and theophylline treatment (OR, 2.5; 95% CI: 1.1-5.4; P = .02). Multiple logistic regression analysis revealed vaginal delivery at our hospital (OR, 3.4; 95% CI: 1.4-8.2; P = .007) and LOS >30 days (OR, 4.4; 95% CI: 1.8-10.6; P = .001) as independent risk factors for S marcescens acquisition. Ribotyping of specimens revealed 5 restriction patterns. CONCLUSION Cases were of lower birth weight than controls, were born by vaginal delivery at our hospital, had longer LOS in NBS, and had greater requirements for respiratory support. Ribotyping of specimens revealed that this outbreak was not clonal.